Next Article in Journal
Updates on the Biological Heterogeneity of Mantle Cell Lymphoma
Previous Article in Journal
Recent Advances in Mesothelioma Treatment: Immunotherapy, Advanced Cell Therapy, and Other Innovative Therapeutic Modalities
Previous Article in Special Issue
Current and Emerging Radiotracers and Technologies for Detection of Advanced Differentiated Thyroid Cancer: A Narrative Review
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Cancers
Volume 17
Issue 4
10.3390/cancers17040695
cancers-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

A Look to the Future: Potential Theranostic Applications in Head and Neck Tumors

by
Jorge D. Oldan
1,*,
Lilja B. Solnes
2,
Bennett B. Chin
3 and
Steven P. Rowe
1,*
1
Molecular Imaging and Therapeutics, Department of Radiology, University of North Carolina, Chapel Hill, NC 27599, USA
2
The Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
3
Department of Radiology, University of Colorado Anschutz Medical Campus, Boulder, CO 80045, USA
*
Authors to whom correspondence should be addressed.
Cancers 2025, 17(4), 695; https://doi.org/10.3390/cancers17040695
Submission received: 28 December 2024 / Revised: 12 February 2025 / Accepted: 15 February 2025 / Published: 19 February 2025
(This article belongs to the Special Issue Head and Neck Cancer: Advanced PET/CT and MRI Imaging with a Focus on Current and Emerging Molecular Theranostics)
Browse Figures
Versions Notes

Simple Summary

Theranostics, which means using one radioactive drug to decide whether a related radioactive drug with a similar chemical shape is useful, is a growing field in finding and treating cancer. We review a number of these pairs of drugs specifically being studied for tumors of the head and neck and describe the clinical studies on patients that have been conducted already for each drug pair. We also discuss drugs that have not been tested in human patients yet to give an idea of the future of the field.

Abstract

Theranostics, the practice of using a diagnostic radiopharmaceutical to guide radiotherapy with a chemically identical (or nearly identical) therapeutic radiopharmaceutical, is an exciting new field under development within the auspices of nuclear medicine. We aim to provide a narrative review of the areas of theranostics use and development which are occurring specifically in the head and neck, with attention to the therapeutic use of existing diagnostically used radiotracers such as agents that target prostate-specific membrane antigen (PSMA) and somatostatin receptors (e.g., DOTATATE derivatives), as well as developing classes of radiotracers such as those targeting fibrinogen-activating protein (FAP) and carbonic anhydrase IX (CAIX), as well as new meta-iodo-benzylguanidine (MIBG) derivatives. Most of those agents are still at the preclinical or early clinical stages of development, but as this is an emerging field, we aim to both outline current progress and suggest future directions.

1. Introduction

The idea of theranostics is that the same (or a very similar) scaffold that is of diagnostic use may also be of therapeutic use by replacing a gamma- or positron-emitting diagnostic radionuclide with a chemically similar beta- or alpha-emitting therapeutic radionuclide. While something of a “buzzword” in recent times, the principle actually dates back to 1936 with the use of iodine-131 sodium iodide as a therapeutic [1], which was followed by various radionuclides for skeletal metastases beginning in the 1950s. Eventually, other targeted radiotracers for diagnostic imaging were leveraged with their theranostic “twins”, such as iodine-131 m-iodobenzylguanidine (131I-MIBG) for neural crest tumors in the 1980s. The actual term, “theranostics”, appeared in the 1990s with the proposal of the somatostatin model, with the diagnostic positron emission tomography (PET) agent 68Ga-DOTATATE being U.S. Food and Drug Administration (FDA)-approved in 2016, followed by the companion therapeutic, 177Lu-DOTATATE (Lutathera) in 2018 [1].
One challenge in the head and neck specifically is that by far the most common head and neck malignancy, squamous cell carcinoma, does not have a specific agent targeted to it, meaning that there remains significant work to be conducted on the preclinical side to delineate targets and appropriate imaging and therapeutic molecules. The use of radioiodine for well-differentiated thyroid cancers has been well described elsewhere and is discussed in another manuscript in this special issue.
However, other specialized diagnostic radiotracers, such as those targeting somatostatin receptors (such as DOTATATE) or the prostate-specific membrane antigen (PSMA) such as 68Ga-PSMA-11 or 18F-DCFPyL/piflufolastat F 18, have been converted into therapeutic agents, and these have begun to be explored in the head and neck. MIBG analogs is well explored, and 131I-MIBG has been used in multiple contexts. A variety of new radiotracers are under development as well, such as fibrinogen-activating protein (FAP) inhibitors and binders, carbonic anhydrase IX (CAIX) inhibitors and monoclonal antibodies, and CXCR4-targeting agents [2]. Explorations of theranostics using modifications of some of these agents have been performed as well, though often not in the head and neck.
In this review, we (1) describe the promising targets in head and neck cancer that might be leveraged for theranostic applications, (2) discuss the potential limitations of current imaging approaches, and (3) provide insight into the applicability of future agents. An overview of agents is provided in Table 1; an overview of the existing data (including case reports) for the efficacy of each theranostic is provided in Table 2.

2. 2-Deoxy-2-[18F]fluoro-D-glucose (FDG)

The most common diagnostic agent used in PET, 2-deoxy-2-[18F]fluoro-D-glucose (FDG), is a poor choice for theranostics for a number of reasons. While there are therapeutic radiohalogens that can be used to create radiotracers that utilize similar radiochemistry [35], those radionuclides tend to be much larger than fluorine-18 and would perturb the nature of some small molecules such as FDG. In addition, no specific agent targeted at glucose transporters currently exists [36]. One way around this would be using Cerenkov radiation from FDG to activate doxorubicin for chemotherapy [37]; in vitro proof-of-concept studies have explored that [37], but further development has not been published as of yet.

3. Prostate-Specific Membrane Antigen (PSMA)

It has been known since the first scans that PSMA-based agents, while targeted at cancer of the prostate, are taken up heavily in the salivary glands, and this is a source of the sialotoxicity of some therapeutic agents (as high as three-quarters with some 225Ac agents) [38]. Recently, attempts have been made to utilize this to treat salivary tumors (usually adenoid cystic carcinoma or salivary duct cancer) with PSMA-targeted theranostic agents [39], particularly given the success of 177Lu-PSMA-617 for prostate cancer in the VISION [40] and TheraP trials [41]. There have been early trials suggesting a dramatic response [3], stabilization of disease and pain control [4,5], or at least pain reduction [6] in isolated cases (usually 1–6 patients). However, at least one trial found insufficient tumor doses to continue [7], and the largest trial (15 patients) showed stable disease in less than a third of patients with adenoid cystic carcinoma and none in salivary duct carcinoma [8]. A number of clinical trials have been started to investigate the theranostic potential of PSMA-targeted agents in adenoid cystic carcinoma, but none have reported findings as of yet [39].
Some thyroid cancers express PSMA as well [39,42]. However, there seems to be significant heterogeneity among lesions in terms of uptake of radioiodine, FDG uptake, and PSMA-targeted radiotracer uptake [43]. Radioactive therapy of well-differentiated thyroid cancer usually begins (and often ends) with radioiodine, but in iodine-refractory cases, other tracers are often explored. PET in refractory iodine-avid tumors shows detection rates from 25 to 100%, but generally less than FDG [42]. There were two trials of 177Lu-PSMA in three patients [9,10], with mixed results. In one study, five patients with widely metastatic thyroid cancer were scanned, finding lesions not seen on FDG-PET, two were treated, and one showed improvement (the other progressed) [9]. The other was a trial on a single patient after tyrosine kinase inhibitors failed; the patient showed temporary improvement but ultimately progressed [10]. In both cases, there was significant uptake in tumors before treatment.
Endolymphatic sac tumors have been shown to have uptake with PSMA-targeted radiotracers and 68Ga-DOTATATE [44], but therapeutic applications have yet to be explored. Nonetheless, those findings hint at the overall big picture. Just as with chemotherapeutic regimens with targeted agents, we are moving into an era where the expression of an appropriate target for targeted radioligand therapy may be more important than the cell of origin.

4. Somatostatin Receptor Inhibitors (DOTATATE)

Paragangliomas, including head and neck paragangliomas, take up radiotracers targeted against the somatostatin receptor, such as labeled peptides based on DOTATATE (Figure 1), which has already shown success in treating midgut neuroendocrine tumors in the NETTER-1 trial that led to FDA approval of 177Lu-DOTATATE [45]. Multiple cases have been treated with 90Y-DOTATATE or, more commonly, 177Lu-DOTATATE, usually with some mixture of stabilization of disease and partial response. Of those, the largest, and also most heterogeneous study, was a retrospective evaluation of 30 patients with pheochromocytoma and paraganglioma, 18 of whom had head and neck paragangliomas, treated with a mixture of 177Lu- and 90Y-DOTATATE or DOTATOC. That study showed 63% stable disease and 20% partial response [11]. A study of 14 patients treated with 177Lu-DOTATATE showed some decrease in uptake in 10 of 14 patients, with the best results in jugulotympanic paraganglioma [12]. Another study, which consisted of nine patients with inoperable head and neck paragangliomas treated with 90Y-, or a mixture of 90Y- and 177Lu-labeled DOTATATE, showed at least stable disease in all patients (four partial response (PR), five stable disease (SD)) [13]. A study of seven patients with head and neck paragangliomas (three carotid, three jugulotympanic, one combination) treated with 177Lu-DOTATATE showed at least stable disease in all and a decrease in tumor volume in four [14]. One study of four patients with neck and mediastinal paraganglioma treated with 177Lu-DOTATATE showed stable or partial response in all [15]. There is one case report of a complete response of a carotid body paraganglioma to 177Lu-DOTATATE [16] and another of stable disease with 90Y- and 177Lu-DOTATATE [17]. Initial results are thus promising, though a larger clinical trial is necessary.
Meningiomas have been known to express somatostatin receptors since the days of Octreoscan, and also unsurprisingly take up DOTATATE (Figure 2); interest in 177Lu-DOTATATE for progressive, treatment-resistant meningioma has existed for a few decades [46], with uptake correlating with receptor expression [47] and possibly negatively with metabolic rate [48], as with many other tumors. Early case reports show stable disease in the short term [18,19] and diagnosis of the occasional lung metastasis [49], mixed with the occasional lack of efficacy [20]. A number of small studies have at least shown the reasonable possibility of disease control. One study of 20 patients with unresectable, progressive meningioma treated with 177Lu-DOTATATE showed stable disease in half, predominantly in patients with higher 68Ga-DOTATATE uptake [21]; another of four showed stable disease in half [22]. A phase I clinical trial (NCT 03971461) of 14 patients with progressive meningiomas again showed stable disease in half for at least 6 months [23]; there is a phase II study (NCT04082520) ongoing. Another study with extended (median 5-year) follow-up of 42 patients mostly treated with 177Lu-DOTATATE (a few received 90Y-DOTATOC) had a 57% disease control rate, median PFS of 16 months, and median OS of 36 months; 6 were retreated with PFS and OS of 6.5 and 17 months, respectively [24].
There is some suggestion, starting with an early case report [25], of intraarterial administration succeeding where intravenous failed; a later study of eight patients treated both intravenously and intraarterially showed better dose and retention time by intraarterial administration, stable disease in seven of eight at 4 weeks and median time to progression of 8.9 months [26]; similarly, a later study of thirteen patients undergoing intraarterial therapy had eight with stable disease, one with partial remission, and one with complete remission [27]. It is thus possible intraarterial administration may have a better chance of achieving disease control.

5. Fibroblast-Activating Protein (FAP)

Fibroblast-activating protein (FAP) is the target of a new series of agents, most of them inhibitors (i.e., FAPI agents), such as 68Ga-FAPI-04 [50] and 68Ga-FAPI-46 [51]. Non-inhibitor molecules, such as peptide 68Ga-FAP-2286, are also under investigation and have shown promising results in certain cancer types [52]. While PSMA and DOTATATE bind specific receptors on the tumor itself (thus being theoretically more specific as they only bind to tumors with that receptor), FAP-targeted agents respond to the tumor microenvironment and bind to the cancer-associated fibroblasts (CAFs) surrounding many tumors. Those agents have already shown significant promise in the diagnostic space [53], with less background heart, liver, and brain uptake than FDG, the standard radiotracer for many tumor types with significant numbers of CAFs [54]. FAP-targeted agents may be more sensitive for bone metastases and radioiodine-negative thyroid cancers than FDG [54], as well as for gastrointestinal cancers [55]. However, as might be expected, they show uptake in fibrotic processes such as myelofibrosis, reactive nodes, arthritis, thyroiditis, and follicular thyroid adenoma, and the question of their effectiveness vis-à-vis FDG remains open [54]. There are also questions regarding the inter-reader reproducibility of these findings. One way or another, there has been increasing interest in them as radionuclide therapies.
While this remains very much at the research stage, there have been a few scattered cases of FAP-targeted agents being used in a theranostic capacity. For example, an agent with a related chemical structure (i.e., based on the (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine scaffold [56]), 177Lu-DOTAGA.(SA.FAPi)2, has undergone a clinical trial of 15 patients with radioiodine-refractory and tyrosine kinase inhibitor-refractory differentiated thyroid cancer [28], with three patients having partial response and another four demonstrating stable disease (none showed complete response). It was also tried in one patient with medullary thyroid cancer, resulting in a decrease in the size of the neck mass with improvement of quality of life [29]. Another agent with the FAP-binding scaffold conjugated to ethylene blue (an albumin binder that increases circulation time), 177Lu-EB-FAPI (also known as 177Lu-LNC1004), was tested in a cohort of twelve patients with differentiated thyroid cancer and showed partial response in three patients and stable disease in another seven [30].
Among cases where the diagnostic radionuclide was switched out for a therapeutic analog, 177Lu-FAPI-46 has been described in multiple case reports. For example, in one case of differentiated thyroid cancer, a patient achieved stable disease [31]. Further, stable disease was also noted in a case of anaplastic thyroid cancer [32]; a mixed response was described in a case of metastatic nasopharyngeal cancer [33]; and symptomatic improvement was noted in a case of MEN 2A with medullary thyroid carcinoma as well as sacral paraganglioma and bilateral pheochromocytoma which did not take up radiolabeled DOTATATE or MIBG [34]. Dosimetry has been studied with the related agent, 177Lu-FAPI-04, in at least one patient with thyroid cancer [57], but efficacy has yet to be determined.

6. Carbonic Anhydrase IX (CAIX) Inhibitors

CAIX is a transmembrane enzyme that is often upregulated in hypoxic tumor microenvironments, as it regulates the acidity of tumor cells, but it can be constitutively expressed when there are mutations [58]; it also encourages metastatic properties such as decreased cell adhesion, activation of proteases, induction of vascularization, and enhancement of motility and migration [59]. High stromal expression of CAIX correlates negatively with survival [60]. It has been studied in head and neck extensively for assessment of hypoxia [61], including with humanized antibodies such as girentuximab [62] that are beginning to be explored therapeutically in cancers that express CAIX [63], such as renal cell carcinoma. Outside of direct theranostic applications, the role of hypoxia as a predictive and prognostic biomarker in patients with head and neck cancer suggests an important role for imaging of CAIX—i.e., that higher uptake of CAIX-targeted agents might be used to select appropriate therapeutic regimens and might also be negatively associated with patient outcomes. A mouse model in which CAIX-targeting has been leveraged to localize yttrium-90 and indium-111 to tumors has been explored [64]. However, theranostic applications in the head and neck have yet to be studied in humans.

7. CXCR4

While promising in hematopoietic malignancies such as lymphoma [65] and multiple myeloma and other diseases such as myelofibrosis and primary aldosteronism [66], agents targeted to CXCR4, most prominently 68Ga-pentixafor, are not well studied for head and neck cancers. The agent, however, has been studied for glioblastoma, with a database of 68Ga-pentixafor images of glioblastoma patients constructed [67]. At least one study of 19 patients shows that it is useful for assessing the presence of CXCR4 receptors in this tumor [68] and may have future potential in this area [69], with various peptides (most prominently 177Lu-Lu-DOTAT-POL3026) being shown to have activity against CXCR4-bearing tumor cells in vitro [70].

8. meta-I-benzylguanidine (MIBG) Derivatives

Replacing the diagnostic radionuclide iodine-123 with the therapeutic radionuclide iodine-131 on the adrenergic receptor-targeted compound MIBG has long been used in the treatment of metastatic pheochromocytoma and paraganglioma (which express adrenergic receptors). Indeed, high-specific-activity 131I-MIBG was the only United States Food and Drug Administration-approved agent for those indications [71] until it was recently withdrawn from the market.
In regards to head and neck paraganglioma, however, those tumors are actually commonly false-negative on MIBG scans [72], making adrenergic receptors a less attractive molecular target, with at least one purely diagnostic study of 131I-MIBG showing low sensitivity for head and neck paraganglioma [73]. Instead, such tumors often express somatostatin receptors and agents such as 177Lu-DOTATATE may be more worthwhile to explore and may also be significantly less toxic with fewer serious adverse events [74].

9. Discussion

The field of theranostics is quite active elsewhere in the body, with FDA-approved agents like 177Lu-DOTATATE and 177Lu-PSMA-617 being well-studied and in widespread use for neuroendocrine tumors [45] and prostate cancer [40,41]. Attempts to extend these agents to other tumors, specifically in the head and neck, have been much more limited in response, likely due to the lack of a good molecular target in most cases—the vast majority of head and neck cancers are aerodigestive tract squamous cell carcinomas, after all, for which no known specific target exists.
DOTATATE has shown the best results, likely due to the presence of SSTR receptors on paragangliomas just as on midgut neuroendocrine tumors. Early studies in tens of patients with head and neck paragangliomas do seem to show a mixture of partial response and stabilization of disease [11,12,13,45], similar to that on midgut tumors. Similarly, trials on progressive, treatment-resistant meningiomas show stabilization of disease in about half [21,23,24]; further trials are ongoing, and there is the possibility intraarterial administration of the drug may improve its efficacy.
The picture is unclear or less rosy for other groups of agents. For PSMA agents, there are case reports of initial success for adenoid cystic carcinoma, but early trials show stabilization of disease at best [7,8]. Use of these agents for iodine-refractory thyroid cancer similarly shows mixed results at best [9,10]. FAP agents show a mix of stabilization and partial response in differentiated thyroid cancer [28,29] and are under further study. CAIX and CXCR4 have not been studied in humans at the present time.
MIBG derivatives are a case where the theranostic agent is actually produced and FDA-approved but withdrawn from the market by the manufacturer due to limited usage and fixed costs. Head and neck paragangliomas, unlike other locations, are famously false-negative on MIBG scans [72], suggesting this may not be a promising molecular target in the head and neck, with DOTATATE above being preferred instead [74].
The toxicities of PSMA agents, in particular 177Lu-PSMA-617, are well described in the multiple trials that have been performed [40,41]. These include bone marrow suppression effects such as thrombocytopenia, anemia, and leukopenia, and decreased renal function, reaching Grade 3 or 4 in 5–15% of cases; salivary gland toxicity is also well documented. The toxicities of 177Lu-DOTATATE have similarly been explored in multiple large studies, with Grade 3–4 myelosuppression or decreased renal function being somewhat rarer (0–3%) but a carcinoid crisis occasionally occurring (<1%) and needing to be treated with SSTR antagonists. 177Lu-DOTATATE also requires simultaneous administration of amino acids over several hours to prevent nephrotoxicity [45]. Data for the other agents are much more limited, but a first-in-human, dose escalation FAP agent trial similarly found hematotoxicity to limit dose escalation in some patients [30].

10. Conclusions

In recent years, theranostic approaches in which targeted diagnostic and therapeutic radiotracers are combined to provide optimized precision medicine for patients have radically altered the treatment paradigms for patients with multiple different cancers [40,75]. The emergence of new radioligands, improvements in the availability and side-effect mitigation of α-particle emitting radionuclides, and the incorporation of new methods such as artificial intelligence into patient selection should all contribute to fulfilling the promise of the theranostic paradigm [76].
A number of promising new approaches outside of the imaging field are being developed. The theranostic genome, an exciting new listing of potential theranostic targets in the genome [77], offers the possibility of discovering a wealth of future new molecular targets, such as the mTOR pathway for photodynamic therapy [78].
Specifically, in regard to head and neck cancer, theranostics remains in its infancy. We have hints that DOTATATE-derived therapeutic agents may prove useful in head and neck paragangliomas and meningiomas, as they are in the remainder of the body, and that FAP-targeted agents may prove useful in multiple cancers, such as undifferentiated thyroid cancer. Applications of other molecular targets largely remain to be seen. Significant work remains—but the rich pipeline of new agents and targets should ensure a wealth of new information and opportunities for improvements in patient care.

Author Contributions

Conceptualization, J.D.O. and S.P.R.; writing—original draft preparation, J.D.O.; writing—review and editing, J.D.O., L.B.S., B.B.C. and S.P.R. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Informed Consent Statement

This is a review article summarizing existing literature, and hence there are no patients.

Conflicts of Interest

SPR is a consultant for Lantheus, Telix, and Blue Earth Diagnostics. JDO consulted for Telix in the past.

References

  1. Modoni, S.; Frangos, S.; Iakovou, I.; Boero, M.; Mansi, L. Theragnostics before we found its name. Q. J. Nucl. Med. Mol. Imaging 2021, 65, 299–305. [Google Scholar] [CrossRef] [PubMed]
  2. Oldan, J.D.; Pomper, M.G.; Werner, R.A.; Higuchi, T.; Rowe, S.P. The cutting edge: Promising oncology radiotracers in clinical development. Diagn. Interv. Imaging 2024, 105, 400–406. [Google Scholar] [CrossRef]
  3. Wang, G.; Zhou, M.; Zang, J.; Jiang, Y.; Chen, X.; Zhu, Z.; Chen, X. A pilot study of (68) Ga-PSMA-617 PET/CT imaging and (177)Lu-EB-PSMA-617 radioligand therapy in patients with adenoid cystic carcinoma. EJNMMI Res. 2022, 12, 52. [Google Scholar] [CrossRef]
  4. Klein Nulent, T.J.W.; van Es, R.J.J.; Willems, S.M.; Braat, A.; Devriese, L.A.; de Bree, R.; de Keizer, B. First experiences with (177)Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancer. EJNMMI Res. 2021, 11, 126. [Google Scholar] [CrossRef] [PubMed]
  5. Terroir, M.; Lamesa, C.; Krim, M.; Vija, L.; Texier, J.S.; Cassou-Mounat, T.; Delord, J.P.; Vallot, D.; Courbon, F. RadioLigand Therapy with [(177)Lu]Lu-PSMA-617 for Salivary Gland Cancers: Literature Review and First Compassionate Use in France. Pharmaceuticals 2023, 16, 754. [Google Scholar] [CrossRef] [PubMed]
  6. Has Simsek, D.; Kuyumcu, S.; Agaoglu, F.Y.; Unal, S.N. Radionuclide Therapy with 177Lu-PSMA in a Case of Metastatic Adenoid Cystic Carcinoma of the Parotid. Clin. Nucl. Med. 2019, 44, 764–766. [Google Scholar] [CrossRef]
  7. Civan, C.; Kasper, S.; Berliner, C.; Fragoso-Costa, P.; Grunwald, V.; Pogorzelski, M.; Schaarschmidt, B.M.; Lang, S.; Kersting, D.; Nader, M.; et al. PSMA-Directed Imaging and Therapy of Salivary Gland Tumors: A Single-Center Retrospective Study. J. Nucl. Med. 2023, 64, 372–378. [Google Scholar] [CrossRef]
  8. Van Herpen, C.M.L.; Uijen, M.; van Ruitenbeek, N.; Driessen, C.M.L.; Gotthardt, M.; Nagarajah, J. 177Lu-PSMA radioligand therapy for patients with recurrent/metastatic (R/M) salivary gland cancer (SGC): A phase II pilot study. J. Clin. Oncol. 2023, 41, 6099. [Google Scholar] [CrossRef]
  9. de Vries, L.H.; Lodewijk, L.; Braat, A.; Krijger, G.C.; Valk, G.D.; Lam, M.; Borel Rinkes, I.H.M.; Vriens, M.R.; de Keizer, B. (68)Ga-PSMA PET/CT in radioactive iodine-refractory differentiated thyroid cancer and first treatment results with (177)Lu-PSMA-617. EJNMMI Res. 2020, 10, 18. [Google Scholar] [CrossRef]
  10. Assadi, M.; Ahmadzadehfar, H. (177)Lu-DOTATATE and (177)Lu-prostate-specific membrane antigen therapy in a patient with advanced metastatic radioiodine-refractory differentiated thyroid cancer after failure of tyrosine kinase inhibitors treatment. World J. Nucl. Med. 2019, 18, 406–408. [Google Scholar] [CrossRef]
  11. Rubino, M.; Di Stasio, G.D.; Bodei, L.; Papi, S.; Rocca, P.A.; Ferrari, M.E.; Fodor, C.I.; Bagnardi, V.; Frassoni, S.; Mei, R.; et al. Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): Results from a single institutional retrospective analysis. Endocrine 2024, 84, 704–710. [Google Scholar] [CrossRef] [PubMed]
  12. Estevao, R.; Duarte, H.; Lopes, F.; Fernandes, J.; Monteiro, E. Peptide receptor radionuclide therapy in head and neck paragangliomas—Report of 14 cases. Rev. Laryngol. Otol. Rhinol. 2015, 136, 155–158. [Google Scholar]
  13. Puranik, A.D.; Kulkarni, H.R.; Singh, A.; Baum, R.P. Peptide receptor radionuclide therapy with (90)Y/ (177)Lu-labelled peptides for inoperable head and neck paragangliomas (glomus tumours). Eur. J. Nucl. Med. Mol. Imaging 2015, 42, 1223–1230. [Google Scholar] [CrossRef]
  14. Roll, W.; Muther, M.; Sporns, P.B.; Zinnhardt, B.; Suero Molina, E.; Seifert, R.; Schafers, M.; Weckesser, M.; Stegger, L.; Beule, A.G.; et al. Somatostatin Receptor-Targeted Radioligand Therapy in Head and Neck Paraganglioma. World Neurosurg. 2020, 143, e391–e399. [Google Scholar] [CrossRef]
  15. Zovato, S.; Kumanova, A.; Dematte, S.; Sansovini, M.; Bodei, L.; Di Sarra, D.; Casagranda, E.; Severi, S.; Ambrosetti, A.; Schiavi, F.; et al. Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in individuals with neck or mediastinal paraganglioma (PGL). Horm. Metab. Res. 2012, 44, 411–414. [Google Scholar] [CrossRef]
  16. Yadav, M.P.; Raju, S.; Ballal, S.; Bal, C. Complete Response to 177 Lu-DOTATATE PRRT in a 9-Year-Old Child with Metastatic Carotid Body Paraganglioma. Clin. Nucl. Med. 2024, 49, e33–e34. [Google Scholar] [CrossRef]
  17. Lon, I.; Kunikowska, J.; Jedrusik, P.; Gora, J.; Toutounchi, S.; Placha, G.; Gaciong, Z. Familial SDHB gene mutation in disseminated non-hypoxia-related malignant paraganglioma treated with [(90)Y]Y/[(177)Lu]Lu-DOTATATE. Intractable Rare Dis. Res. 2021, 10, 207–213. [Google Scholar] [CrossRef]
  18. Zahid, A.; Johnson, D.R.; Kizilbash, S.H. Efficacy of (177)Lu-Dotatate Therapy in the Treatment of Recurrent Meningioma. Mayo Clin. Proc. Innov. Qual. Outcomes 2021, 5, 236–240. [Google Scholar] [CrossRef]
  19. Pirisino, R.; Filippi, L.; D’Agostini, A.; Bagni, O. Management of a Patient with Metastatic Gastrointestinal Neuroendocrine Tumor and Meningioma Submitted to Peptide Receptor Radionuclide Therapy with 177 Lu-DOTATATE. Clin. Nucl. Med. 2022, 47, e692–e695. [Google Scholar] [CrossRef]
  20. Wrange, E.K.M.; Harders, S.M.W. A rare case of metastatic atypical meningioma that highlights the shortcomings of treatment options at present. Acta Radiol. Open 2022, 11, 20584601221109919. [Google Scholar] [CrossRef]
  21. Seystahl, K.; Stoecklein, V.; Schuller, U.; Rushing, E.; Nicolas, G.; Schafer, N.; Ilhan, H.; Pangalu, A.; Weller, M.; Tonn, J.C.; et al. Somatostatin receptor-targeted radionuclide therapy for progressive meningioma: Benefit linked to 68Ga-DOTATATE/-TOC uptake. Neuro Oncol. 2016, 18, 1538–1547. [Google Scholar] [CrossRef] [PubMed]
  22. Muther, M.; Roll, W.; Brokinkel, B.; Zinnhardt, B.; Sporns, P.B.; Seifert, R.; Schafers, M.; Weckesser, M.; Stegger, L.; Stummer, W.; et al. Response assessment of somatostatin receptor targeted radioligand therapies for progressive intracranial meningioma. Nuklearmedizin 2020, 59, 348–355. [Google Scholar] [CrossRef] [PubMed]
  23. Kurz, S.C.; Zan, E.; Cordova, C.; Troxel, A.B.; Barbaro, M.; Silverman, J.S.; Snuderl, M.; Zagzag, D.; Kondziolka, D.; Golfinos, J.G.; et al. Evaluation of the SSTR2-targeted Radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as Imaging Biomarker in Patients with Intracranial Meningioma. Clin. Cancer Res. 2024, 30, 680–686. [Google Scholar] [CrossRef]
  24. Severi, S.; Grassi, I.; Bongiovanni, A.; Nicolini, S.; Marini, I.; Arpa, D.; Ranallo, N.; Azzali, I.; Di Iorio, V.; Sarnelli, A.; et al. Peptide Receptor Radionuclide Therapy in Advanced Refractory Meningiomas: Efficacy and Toxicity in a Long Follow-up. J. Nucl. Med. 2024, 65, 1409–1415. [Google Scholar] [CrossRef]
  25. Braat, A.; Snijders, T.J.; Seute, T.; Vonken, E.P.A. Will (177)Lu-DOTATATE Treatment Become More Effective in Salvage Meningioma Patients, When Boosting Somatostatin Receptor Saturation? A Promising Case on Intra-arterial Administration. Cardiovasc. Intervent. Radiol. 2019, 42, 1649–1652. [Google Scholar] [CrossRef]
  26. Puranik, A.D.; Dev, I.D.; Rangarajan, V.; Kulkarni, S.; Shetty, N.; Gala, K.; Sahu, A.; Bhattacharya, K.; Dasgupta, A.; Chatterjee, A.; et al. PRRT with Lu-177 DOTATATE in Treatment-Refractory Progressive Meningioma: Initial Experience from a Tertiary-Care Neuro-Oncology Center. Neurol. India 2024, 72, 278–284. [Google Scholar] [CrossRef]
  27. Amerein, A.; Maurer, C.; Kircher, M.; Gable, A.; Krebold, A.; Rinscheid, A.; Viering, O.; Pfob, C.H.; Bundschuh, R.A.; Behrens, L.; et al. Intraarterial Administration of Peptide Receptor Radionuclide Therapy in Patients with Advanced Meningioma: Initial Safety and Efficacy. J. Nucl. Med. 2024, 65, 1911–1916. [Google Scholar] [CrossRef]
  28. Ballal, S.; Yadav, M.P.; Moon, E.S.; Roesch, F.; Kumari, S.; Agarwal, S.; Tripathi, M.; Sahoo, R.K.; Mangu, B.S.; Tupalli, A.; et al. Novel Fibroblast Activation Protein Inhibitor-Based Targeted Theranostics for Radioiodine-Refractory Differentiated Thyroid Cancer Patients: A Pilot Study. Thyroid 2022, 32, 65–77. [Google Scholar] [CrossRef]
  29. Ballal, S.; Yadav, M.P.; Moon, E.S.; Rosch, F.; ArunRaj, S.T.; Agarwal, S.; Tripathi, M.; Sahoo, R.K.; Bal, C. First-in-Human Experience with 177Lu-DOTAGA.(SA.FAPi)2 Therapy in an Uncommon Case of Aggressive Medullary Thyroid Carcinoma Clinically Mimicking as Anaplastic Thyroid Cancer. Clin. Nucl. Med. 2022, 47, e444–e445. [Google Scholar] [CrossRef]
  30. Fu, H.; Huang, J.; Zhao, T.; Wang, H.; Chen, Y.; Xu, W.; Pang, Y.; Guo, W.; Sun, L.; Wu, H.; et al. Fibroblast Activation Protein-Targeted Radioligand Therapy with 177Lu-EB-FAPI for Metastatic Radioiodine-Refractory Thyroid Cancer: First-in-Human, Dose-Escalation Study. Clin. Cancer Res. 2023, 29, 4740–4750. [Google Scholar] [CrossRef]
  31. Fu, H.; Huang, J.; Sun, L.; Wu, H.; Chen, H. FAP-Targeted Radionuclide Therapy of Advanced Radioiodine-Refractory Differentiated Thyroid Cancer with Multiple Cycles of 177 Lu-FAPI-46. Clin. Nucl. Med. 2022, 47, 906–907. [Google Scholar] [CrossRef] [PubMed]
  32. Assadi, M.; Rekabpour, S.J.; Jafari, E.; Divband, G.; Nikkholgh, B.; Amini, H.; Kamali, H.; Ebrahimi, S.; Shakibazad, N.; Jokar, N.; et al. Feasibility and Therapeutic Potential of 177Lu-Fibroblast Activation Protein Inhibitor-46 for Patients with Relapsed or Refractory Cancers: A Preliminary Study. Clin. Nucl. Med. 2021, 46, e523–e530. [Google Scholar] [CrossRef] [PubMed]
  33. Fu, K.; Pang, Y.; Zhao, L.; Lin, L.; Wu, H.; Sun, L.; Lin, Q.; Chen, H. FAP-targeted radionuclide therapy with [(177)Lu]Lu-FAPI-46 in metastatic nasopharyngeal carcinoma. Eur. J. Nucl. Med. Mol. Imaging 2022, 49, 1767–1769. [Google Scholar] [CrossRef] [PubMed]
  34. Barashki, S.; Divband, G.; Askari, E.; Amini, H.; Aryana, K. Fibroblast Activation Protein Inhibitor Imaging and Therapy in a Patient with Multiple Endocrine Neoplasia Type 2A Syndrome. Clin. Nucl. Med. 2022, 47, e284–e286. [Google Scholar] [CrossRef]
  35. Rowe, S.P.; Drzezga, A.; Neumaier, B.; Dietlein, M.; Gorin, M.A.; Zalutsky, M.R.; Pomper, M.G. Prostate-Specific Membrane Antigen-Targeted Radiohalogenated PET and Therapeutic Agents for Prostate Cancer. J. Nucl. Med. 2016, 57, 90S–96S. [Google Scholar] [CrossRef]
  36. Lee, D.Y.; Li, K.C. Molecular theranostics: A primer for the imaging professional. AJR Am. J. Roentgenol. 2011, 197, 318–324. [Google Scholar] [CrossRef]
  37. Quintos-Meneses, H.A.; Aranda-Lara, L.; Morales-Avila, E.; Torres-Garcia, E.; Camacho-Lopez, M.A.; Sanchez-Holguin, M.; Luna-Gutierrez, M.A.; Ramirez-Duran, N.; Isaac-Olive, K. In vitro irradiation of doxorubicin with (18)F-FDG Cerenkov radiation and its potential application as a theragnostic system. J. Photochem. Photobiol. B 2020, 210, 111961. [Google Scholar] [CrossRef]
  38. Parida, G.K.; Panda, R.A.; Bishnoi, K.; Agrawal, K. Efficacy and Safety of Actinium-225 Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Prostate Cancer: A Systematic Review and Metanalysis. Med. Princ. Pract. 2023, 32, 178–191. [Google Scholar] [CrossRef]
  39. Wang, J.H.; Kiess, A.P. PSMA-targeted therapy for non-prostate cancers. Front. Oncol. 2023, 13, 1220586. [Google Scholar] [CrossRef]
  40. Sartor, O.; de Bono, J.; Chi, K.N.; Fizazi, K.; Herrmann, K.; Rahbar, K.; Tagawa, S.T.; Nordquist, L.T.; Vaishampayan, N.; El-Haddad, G.; et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N. Engl. J. Med. 2021, 385, 1091–1103. [Google Scholar] [CrossRef]
  41. Hofman, M.S.; Emmett, L.; Sandhu, S.; Iravani, A.; Buteau, J.P.; Joshua, A.M.; Goh, J.C.; Pattison, D.A.; Tan, T.H.; Kirkwood, I.D.; et al. Overall survival with [(177)Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): Secondary outcomes of a randomised, open-label, phase 2 trial. Lancet Oncol. 2024, 25, 99–107. [Google Scholar] [CrossRef] [PubMed]
  42. Rizzo, A.; Racca, M.; Dall’Armellina, S.; Delgado Bolton, R.C.; Albano, D.; Dondi, F.; Bertagna, F.; Annunziata, S.; Treglia, G. Potential Role of PSMA-Targeted PET in Thyroid Malignant Disease: A Systematic Review. Diagnostics 2023, 13, 564. [Google Scholar] [CrossRef] [PubMed]
  43. Santhanam, P.; Russell, J.; Rooper, L.M.; Ladenson, P.W.; Pomper, M.G.; Rowe, S.P. The prostate-specific membrane antigen (PSMA)-targeted radiotracer (18)F-DCFPyL detects tumor neovasculature in metastatic, advanced, radioiodine-refractory, differentiated thyroid cancer. Med. Oncol. 2020, 37, 98. [Google Scholar] [CrossRef]
  44. Brada, M.D.; Rushing, E.J.; Bachinger, D.; Zoller, L.; Burger, I.A.; Hullner, M.W.; Moch, H.; Huber, A.; Eckhard, A.H.; Rupp, N.J. Immunohistochemical Expression Pattern of Theragnostic Targets SSTR2 and PSMA in Endolymphatic Sac Tumors: A Single Institution Case Series. Head Neck Pathol. 2022, 16, 1012–1018. [Google Scholar] [CrossRef]
  45. Strosberg, J.R.; Caplin, M.E.; Kunz, P.L.; Ruszniewski, P.B.; Bodei, L.; Hendifar, A.; Mittra, E.; Wolin, E.M.; Yao, J.C.; Pavel, M.E.; et al. (177)Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): Final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021, 22, 1752–1763. [Google Scholar] [CrossRef]
  46. van Essen, M.; Krenning, E.P.; Kooij, P.P.; Bakker, W.H.; Feelders, R.A.; de Herder, W.W.; Wolbers, J.G.; Kwekkeboom, D.J. Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. J. Nucl. Med. 2006, 47, 1599–1606. [Google Scholar]
  47. Hanscheid, H.; Sweeney, R.A.; Flentje, M.; Buck, A.K.; Lohr, M.; Samnick, S.; Kreissl, M.; Verburg, F.A. PET SUV correlates with radionuclide uptake in peptide receptor therapy in meningioma. Eur. J. Nucl. Med. Mol. Imaging 2012, 39, 1284–1288. [Google Scholar] [CrossRef]
  48. Dressen, M.S.; Muthukrishnan, A.; Tragon, T.R.; Lieberman, F.S.; Mountz, J.M. Complementary Molecular and Metabolic Characterization of Meningiomas with DOTATATE and FDG-PET: Advancing Treatment Planning and Prognostication. Clin. Nucl. Med. 2019, 44, e26–e27. [Google Scholar] [CrossRef]
  49. Backhaus, P.; Huss, S.; Kosek, V.; Weckesser, M.; Rahbar, K. Lung Metastases of Intracranial Atypical Meningioma Diagnosed on Posttherapeutic Imaging After 177Lu-DOTATATE Therapy. Clin. Nucl. Med. 2018, 43, e184–e185. [Google Scholar] [CrossRef]
  50. Lindner, T.; Loktev, A.; Altmann, A.; Giesel, F.; Kratochwil, C.; Debus, J.; Jager, D.; Mier, W.; Haberkorn, U. Development of Quinoline-Based Theranostic Ligands for the Targeting of Fibroblast Activation Protein. J. Nucl. Med. 2018, 59, 1415–1422. [Google Scholar] [CrossRef]
  51. Loktev, A.; Lindner, T.; Burger, E.M.; Altmann, A.; Giesel, F.; Kratochwil, C.; Debus, J.; Marme, F.; Jager, D.; Mier, W.; et al. Development of Fibroblast Activation Protein-Targeted Radiotracers with Improved Tumor Retention. J. Nucl. Med. 2019, 60, 1421–1429. [Google Scholar] [CrossRef] [PubMed]
  52. Koshkin, V.S.; Kumar, V.; Kline, B.; Escobar, D.; Aslam, M.; Cooperberg, M.R.; Aggarwal, R.R.; de Kouchkovsky, I.; Chou, J.; Meng, M.V.; et al. Initial Experience with (68)Ga-FAP-2286 PET Imaging in Patients with Urothelial Cancer. J. Nucl. Med. 2024, 65, 199–205. [Google Scholar] [CrossRef] [PubMed]
  53. van den Hoven, A.F.; Keijsers, R.G.M.; Lam, M.; Glaudemans, A.; Verburg, F.A.; Vogel, W.V.; Lavalaye, J. Current research topics in FAPI theranostics: A bibliometric analysis. Eur. J. Nucl. Med. Mol. Imaging 2023, 50, 1014–1027. [Google Scholar] [CrossRef]
  54. Guglielmo, P.; Alongi, P.; Baratto, L.; Conte, M.; Abenavoli, E.M.; Buschiazzo, A.; Celesti, G.; Dondi, F.; Filice, R.; Gorica, J.; et al. FAPi-Based Agents in Thyroid Cancer: A New Step towards Diagnosis and Therapy? A Systematic Review of the Literature. Cancers 2024, 16, 839. [Google Scholar] [CrossRef]
  55. Wu, Q.; Wang, C.; Huang, C.; Li, D. Head-to-head comparison of [(68)Ga]Ga-FAPI-04 PET and [(18)F]FDG PET in the detection of cancer recurrence: A systematic review and meta-analysis. Transl. Cancer Res. 2024, 13, 2779–2789. [Google Scholar] [CrossRef]
  56. Slania, S.L.; Das, D.; Lisok, A.; Du, Y.; Jiang, Z.; Mease, R.C.; Rowe, S.P.; Nimmagadda, S.; Yang, X.; Pomper, M.G. Imaging of Fibroblast Activation Protein in Cancer Xenografts Using Novel (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine-Based Small Molecules. J. Med. Chem. 2021, 64, 4059–4070. [Google Scholar] [CrossRef]
  57. Kuyumcu, S.; Kovan, B.; Sanli, Y.; Buyukkaya, F.; Has Simsek, D.; Ozkan, Z.G.; Isik, E.G.; Ekenel, M.; Turkmen, C. Safety of Fibroblast Activation Protein-Targeted Radionuclide Therapy by a Low-Dose Dosimetric Approach Using 177Lu-FAPI04. Clin. Nucl. Med. 2021, 46, 641–646. [Google Scholar] [CrossRef]
  58. Lin, J.; Wang, D.; Liu, J.; Yang, L.; Liu, J. Carbonic anhydrase IX-based tumor imaging and therapy: A review. Sheng Wu Gong Cheng Xue Bao 2023, 39, 116–131. [Google Scholar] [CrossRef]
  59. Gieling, R.G.; Williams, K.J. Carbonic anhydrase IX as a target for metastatic disease. Bioorg. Med. Chem. 2013, 21, 1470–1476. [Google Scholar] [CrossRef]
  60. Brockton, N.; Dort, J.; Lau, H.; Hao, D.; Brar, S.; Klimowicz, A.; Petrillo, S.; Diaz, R.; Doll, C.; Magliocco, A. High stromal carbonic anhydrase IX expression is associated with decreased survival in P16-negative head-and-neck tumors. Int. J. Radiat. Oncol. Biol. Phys. 2011, 80, 249–257. [Google Scholar] [CrossRef]
  61. Huizing, F.J.; Hoeben, B.A.W.; Lok, J.; Boerman, O.C.; Heskamp, S.; Bussink, J. Imaging carbonic anhydrase IX as a method for monitoring hypoxia-related radioresistance in preclinical head and neck cancer models. Phys. Imaging Radiat. Oncol. 2021, 19, 145–150. [Google Scholar] [CrossRef]
  62. Huizing, F.J.; Garousi, J.; Lok, J.; Franssen, G.; Hoeben, B.A.W.; Frejd, F.Y.; Boerman, O.C.; Bussink, J.; Tolmachev, V.; Heskamp, S. CAIX-targeting radiotracers for hypoxia imaging in head and neck cancer models. Sci. Rep. 2019, 9, 18898. [Google Scholar] [CrossRef] [PubMed]
  63. Morgan, K.A.; Wichmann, C.W.; Osellame, L.D.; Cao, Z.; Guo, N.; Scott, A.M.; Donnelly, P.S. Tumor targeted alpha particle therapy with an actinium-225 labelled antibody for carbonic anhydrase IX. Chem. Sci. 2024, 15, 3372–3381. [Google Scholar] [CrossRef] [PubMed]
  64. Iikuni, S.; Ono, M.; Watanabe, H.; Shimizu, Y.; Sano, K.; Saji, H. Cancer radiotheranostics targeting carbonic anhydrase-IX with (111)In- and (90)Y-labeled ureidosulfonamide scaffold for SPECT imaging and radionuclide-based therapy. Theranostics 2018, 8, 2992–3006. [Google Scholar] [CrossRef] [PubMed]
  65. Werner, R.; Haug, A.; Buske, C.; Heidegger, S.; Illert, A.L.; Bassermann, F.; Herhaus, P.; Buck, A.; Duell, J.; Topp, M.S.; et al. CXCR4-targeted Theranostics in Hematooncology: Opportunities and Challenges. Nuklearmedizin 2024, 63, 57–61. [Google Scholar] [CrossRef]
  66. Lindenberg, L.; Ahlman, M.; Lin, F.; Mena, E.; Choyke, P. Advances in PET Imaging of the CXCR4 Receptor: [(68)Ga]Ga-PentixaFor. Semin. Nucl. Med. 2024, 54, 163–170. [Google Scholar] [CrossRef]
  67. Roustaei, H.; Norouzbeigi, N.; Vosoughi, H.; Aryana, K. A dataset of [(68)Ga]Ga-Pentixafor PET/CT images of patients with high-grade Glioma. Data Brief 2023, 48, 109236. [Google Scholar] [CrossRef]
  68. Waheed, A.; Singh, B.; Watts, A.; Kaur, H.; Singh, H.; Dhingra, K.; Ahuja, C.; Madan, R.; Singh, A.; Radotra, B.D. 68 Ga-Pentixafor PET/CT for In Vivo Imaging of CXCR4 Receptors in Glioma Demonstrating a Potential for Response Assessment to Radiochemotherapy: Preliminary Results. Clin. Nucl. Med. 2024, 49, e141–e148. [Google Scholar] [CrossRef]
  69. Wang, Y.; Gao, F. Research Progress of CXCR4-Targeting Radioligands for Oncologic Imaging. Korean J. Radiol. 2023, 24, 871–889. [Google Scholar] [CrossRef]
  70. Waked, A.; Crabbe, M.; Neirinckx, V.; Perez, S.R.; Wellens, J.; Rogister, B.; Benotmane, M.A.; Vermeulen, K. Preclinical evaluation of CXCR4 peptides for targeted radionuclide therapy in glioblastoma. EJNMMI Radiopharm. Chem. 2024, 9, 52. [Google Scholar] [CrossRef]
  71. Pryma, D.A.; Chin, B.B.; Noto, R.B.; Dillon, J.S.; Perkins, S.; Solnes, L.; Kostakoglu, L.; Serafini, A.N.; Pampaloni, M.H.; Jensen, J.; et al. Efficacy and Safety of High-Specific-Activity (131)I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma. J. Nucl. Med. 2019, 60, 623–630. [Google Scholar] [CrossRef] [PubMed]
  72. Taieb, D.; Hicks, R.J.; Hindie, E.; Guillet, B.A.; Avram, A.; Ghedini, P.; Timmers, H.J.; Scott, A.T.; Elojeimy, S.; Rubello, D.; et al. European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur. J. Nucl. Med. Mol. Imaging 2019, 46, 2112–2137. [Google Scholar] [CrossRef] [PubMed]
  73. Arora, S.; Kumar, R.; Passah, A.; Tripathi, M.; Agarwala, S.; Khadgawat, R.; Bal, C. Prospective evaluation of 68Ga-DOTANOC positron emission tomography/computed tomography and 131I-meta-iodobenzylguanidine single-photon emission computed tomography/computed tomography in extra-adrenal paragangliomas, including uncommon primary sites and to define their diagnostic roles in current scenario. Nucl. Med. Commun. 2019, 40, 1230–1242. [Google Scholar] [CrossRef]
  74. Al-Ward, R.; Brondani, V.B.; Sawani, S.; Potter, C.L.; Xu, G.; Waguespack, S.G.; Varghese, J.; Habra, M.A.; Lu, Y.; Jimenez, C. High-Specific-Activity 131 I-MIBG for the Treatment of Advanced Pheochromocytoma and Paraganglioma. Clin. Nucl. Med. 2024, 49, 610–620. [Google Scholar] [CrossRef]
  75. Strosberg, J.; El-Haddad, G.; Wolin, E.; Hendifar, A.; Yao, J.; Chasen, B.; Mittra, E.; Kunz, P.L.; Kulke, M.H.; Jacene, H.; et al. Phase 3 Trial of (177)Lu-Dotatate for Midgut Neuroendocrine Tumors. N. Engl. J. Med. 2017, 376, 125–135. [Google Scholar] [CrossRef]
  76. Solnes, L.B.; Werner, R.A.; Jones, K.M.; Sadaghiani, M.S.; Bailey, C.R.; Lapa, C.; Pomper, M.G.; Rowe, S.P. Theranostics: Leveraging Molecular Imaging and Therapy to Impact Patient Management and Secure the Future of Nuclear Medicine. J. Nucl. Med. 2020, 61, 311–318. [Google Scholar] [CrossRef]
  77. Xu, X.; Jané, P.; Taelman, V.; Jané, E.; Dumont, R.A.; Garama, Y.; Kim, F.; Del Val Gómez, M.; Gariani, K.; Walter, M.A. The Theranostic Genome. Nat. Commun. 2024, 15, 10904. [Google Scholar] [CrossRef]
  78. Zhou, H.; Tang, D.; Yu, Y.; Zhang, L.; Wang, B.; Karges, J.; Xiao, H. Theranostic imaging and multimodal photodynamic therapy and immunotherapy using the mTOR signaling pathway. Nat. Commun. 2023, 14, 5350. [Google Scholar] [CrossRef]
Cancers 17 00695 g001
Figure 1. Images from a 46-year-old woman with a carotid body tumor. (A) Transverse ultrasound image demonstrates a heterogeneously hypoechoic mass (arrow) that is splaying the external carotid artery (ECA) and the internal carotid artery (ICA). (B) The mass was also imaged with axial, T1, contrast-enhanced MRI, where the significant vascularity of the tumor was reflected in avid enhancement (arrow). (C) Maximum intensity projection 68Ga-DOTATATE PET and (D) axial 68Ga-DOTATATE PET/CT images show intense uptake in the mass, suggesting a potential role for theranostics in such tumors.
Figure 1. Images from a 46-year-old woman with a carotid body tumor. (A) Transverse ultrasound image demonstrates a heterogeneously hypoechoic mass (arrow) that is splaying the external carotid artery (ECA) and the internal carotid artery (ICA). (B) The mass was also imaged with axial, T1, contrast-enhanced MRI, where the significant vascularity of the tumor was reflected in avid enhancement (arrow). (C) Maximum intensity projection 68Ga-DOTATATE PET and (D) axial 68Ga-DOTATATE PET/CT images show intense uptake in the mass, suggesting a potential role for theranostics in such tumors.
Cancers 17 00695 g001
Cancers 17 00695 g002
Figure 2. Images from a 48-year-old woman with multi-focal meningiomas. (A,C) Axial 68Ga-DOTATATE PET/CT images demonstrate tense uptake at multiple intracranial sites (arrows) that correspond to enhancing mass lesions on (B,D) contrast-enhanced, post-contrast, T1-weighted MRI (arrows).
Figure 2. Images from a 48-year-old woman with multi-focal meningiomas. (A,C) Axial 68Ga-DOTATATE PET/CT images demonstrate tense uptake at multiple intracranial sites (arrows) that correspond to enhancing mass lesions on (B,D) contrast-enhanced, post-contrast, T1-weighted MRI (arrows).
Cancers 17 00695 g002
Table 1. Overview of agents. FDA-approved pharmaceuticals and uses are indicated by *; others are assumed experimental.
Table 1. Overview of agents. FDA-approved pharmaceuticals and uses are indicated by *; others are assumed experimental.
TargetDiagnostic AgentTherapeutic AgentTargets
PSMA18F-flotufolastat *, 18F-piflufolastat *, 68Ga-PSMA-gozetotide *177Lu-PSMA-617 * (vipivotide tetraxetan)Prostate cancer *, adenoid cystic carcinoma, iodine-refractory well-differentiated thyroid cancer, endolymphatic sac tumor (under study)
DOTATATE68Ga-DOTATATE (gozetotide) *, 68Ga-DOTATOC (edotreotide) *, 64Cu-DOTATATE *177Lu-DOTATATE *, 90Y-DOTATATESSTR-positive neuroendocrine tumors (incl. gastroentericopancreatic, paraganglioma/pheochromocytoma) *, meningioma
FAP68Ga-FAPI-04, 68Ga-FAPI-46, others177Lu-DOTAGA.(SA.FAPi)2, 177Lu-EB-FAPI,
CAIX89Zr-girentuximabNone yetRenal cell cancer
CXCR468Ga-pentixafor177Lu-DOTAT-POL3026Glioblastoma
Alpha2 adreno-ceptor123I-MIBG *131I-MIBG * (no longer made)Neuroblastoma
Table 2. Efficacy and evidence for each tracer. ACC, adenoid cystic carcinoma, DTC, differentiated thyroid cancer; PD = progressive disease, SD = stable disease, PR = partial response, CR = complete response. FDA-approved pharmaceuticals and uses are indicated by *; others are assumed experimental.
Table 2. Efficacy and evidence for each tracer. ACC, adenoid cystic carcinoma, DTC, differentiated thyroid cancer; PD = progressive disease, SD = stable disease, PR = partial response, CR = complete response. FDA-approved pharmaceuticals and uses are indicated by *; others are assumed experimental.
Therapeutic AgentTargetsnEfficacyRef.
177Lu-PSMA-617 *ACC42 PR, 2 mixed[3]
177Lu-PSMA-617 *Salivary gland cancer (mixed)61 SD, 1 PR; 4 pain red[4]
177Lu-PSMA-617 *ACC1SD, Pain reduction[5]
177Lu-PSMA-617 *ACC1PD, Pain reduction[6]
177Lu-PSMA-617 *Salivary gland cancer (mixed)54 PD, 1 SD[7]
177Lu-PSMA-617 *ACC, salivary duct carcinoma154 PD, 3 SD (5 discontinued tx)[8]
177Lu-PSMA-617 *Iodine-refractory DTC21 PD, 1 PR[9]
177Lu-PSMA-617 *Iodine-refractory DTC11 PD[10]
177Lu-DOTATATE *, 90Y-DOTATATE, 90Y-DOTATOCParaganglioma/pheochromocytoma30 4 PD, 19 SD, 7 PR[11]
177Lu-DOTATATE *HN Paraganglioma1410 PR (by SUV)[12]
177Lu-DOTATATE *, 90Y-DOTATATEHN paraganglioma94 PR, 5 SD[13]
177Lu-DOTATATE *HN paraganglioma74 PR, 3 SD[14]
177Lu-DOTATATE *HN/mediastinal paraganglioma42 PR, 2 SD[15]
177Lu-DOTATATE *Carotid body paraganglioma1PR[16]
177Lu-DOTATATE *, 90Y-DOTATATECarotid body paraganglioma1SD[17]
177Lu-DOTATATE *Meningioma (recurrent)1SD[18]
177Lu-DOTATATE *Meningioma (metastatic)1SD[19]
177Lu-DOTATATE *Meningioma (metastatic)1PD[20]
177Lu-DOTATATE *Meningioma (refractory, prog.)2010 PR, 10 SD[21]
177Lu-DOTATATE *Meningioma (progressive)42 PD, 2 SD[22]
177Lu-DOTATATE *Meningioma (progressive)147 PD, 7 SD[23]
177Lu-DOTATATE *, 90Y-DOTATOCMeningioma4223 SD, 1 PR[24]
177Lu-DOTATATE * (IA)Meningioma11 PR[25]
177Lu-DOTATATE * (IA)Meningioma81 PD, 7 SD [26]
177Lu-DOTATATE * (IA)Meningioma133 PD, 8 SD, 1 PR, 1 CR[27]
177Lu-DOTAGA.(SA.FAPi)2RAI/TKI-refractory DTC158 PD, 4 SD, 3 PR[28]
177Lu-DOTAGA.(SA.FAPi)2Medullary thyroid cancer1PR[29]
177Lu-EB-FAPIDTC122 PD, 7 SD, 3 PR[30]
177Lu-FAPI-46DTC1SD[31]
177Lu-FAPI-46Nasopharyngeal cancer1SD[32]
177Lu-FAPI-46Nasopharyngeal cancer1Mixed response[33]
177Lu-FAPI-46MEN 2A (multiple cancers)1Symptomatic only[34]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Oldan, J.D.; Solnes, L.B.; Chin, B.B.; Rowe, S.P. A Look to the Future: Potential Theranostic Applications in Head and Neck Tumors. Cancers 2025, 17, 695. https://doi.org/10.3390/cancers17040695

AMA Style

Oldan JD, Solnes LB, Chin BB, Rowe SP. A Look to the Future: Potential Theranostic Applications in Head and Neck Tumors. Cancers. 2025; 17(4):695. https://doi.org/10.3390/cancers17040695

Chicago/Turabian Style

Oldan, Jorge D., Lilja B. Solnes, Bennett B. Chin, and Steven P. Rowe. 2025. "A Look to the Future: Potential Theranostic Applications in Head and Neck Tumors" Cancers 17, no. 4: 695. https://doi.org/10.3390/cancers17040695

APA Style

Oldan, J. D., Solnes, L. B., Chin, B. B., & Rowe, S. P. (2025). A Look to the Future: Potential Theranostic Applications in Head and Neck Tumors. Cancers, 17(4), 695. https://doi.org/10.3390/cancers17040695

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop