Prostate-Specific Membrane Antigen Radioligand Therapy in Non-Prostate Cancers: Where Do We Stand?
Abstract
:1. Introduction
2. Search Strategies
3. Results
3.1. Preclinical Studies
First Author [Ref.] | Year | Type of Disease | Cell Lines/Mouse Model | Main Findings |
---|---|---|---|---|
Heesch A [27] | 2023 | Breast cancer | Endothelial cell line (HUVEC), benign breast epithelial cell line (MCF-10A), PCa cell line (LNCaP), and TNBC cell lines (MDA-MB-231, MDA-MB-468, BT-20, Hs578T, SUM149PT, SUM1315MO2, HCC1937) | PSMA expression was detected in 91% of the investigated TNBC cell lines. Hypoxic conditions significantly increased the uptake of [177Lu]Lu-PSMA in MDA-MB-231 (0.4% vs. 3.4%) and MCF-10A (0.3% vs. 3.0%). [177Lu]Lu-PSMA-induced apoptosis rates were highest in BT-20- and MDA-MB-231-associated endothelial cells. |
Morgenroth A [28] | 2019 | Breast cancer | - Human breast cancer cell lines (MDA-MB 231 and MCF-7); endothelial cells (HUVEC). - Subcutaneous xenograft. | [177Lu]Lu-PSMA-617 impaired the vitality and angiogenic potential of cells. In vivo, PSMA accumulated specifically in triple-negative breast cancer xenografts. |
Heesch A [29] | 2024 | Breast cancer | - Human breast cancer cell lines MDA-MB-231. - Orthotopic xenograft. | The tumour volume 30 days after therapy was significantly smaller for the single-dose (p < 0.001) and fractionated dose (p < 0.001) groups compared with the control. In the tumour tissue, both therapy groups showed a higher amount of apoptotic cells compared with the control group |
Lu Q [30] | 2023 | HCC | - Human hepatocellular cancer cells HepG2. - Subcutaneous xenograft. | Tumour growth was significantly suppressed in the 37 MBq [177Lu]Lu-PSMA-617, 18.5 MBq [177Lu]Lu-PSMA-617, and 7.4 MBq [177Lu]Lu-EB-PSMA-617 groups compared with the saline group. Median survival was 40, 44, 43, and 30 days, respectively. No healthy organ toxicity was observed. |
3.2. Clinical Studies
First Author [Ref.] | Year | Type of Disease | Patients | 177Lu-PSMA RLT | Main Findings |
---|---|---|---|---|---|
Civan C [31] | 2023 | Salivary gland tumours | 5 | One cycle in three patients and RLT completed in two patients; 6.8 ± 1.4 GBq; time interval 6 weeks | PSMA RLT was well tolerated and stabilized disease in one patient. However, frequent discontinuation after one PSMA RLT cycle and low tumor absorbed doses were shown. |
Klein Nulent TJW [32] | 2021 | Metastatic salivary gland tumours | 6 | One to four cycles; 6.0–7.4 GBq; interval time 6–8 weeks | When tumour targeting was sufficient, palliative PSMA RLT of advanced/metastasized salivary gland cancer may cause a significant relief of tumour-associated discomfort and may induce disease control in one-third of the cases. |
Has Simsek D [33] | 2019 | Adenoid cystic carcinoma of the parotid | 1 | One cycle, 7.5 GBq | The treatment was well tolerated with no side effects reported. Significant but not complete pain relief was expressed by the patient. |
Wang G [34] | 2022 | Adenoid cystic carcinoma | 4 | Up to three cycles; 1.85 GBq; interval time 8–10 weeks | PSMA RLT based on [177Lu]Lu-EB-PSMA-617 may be a promising treatment for adenoid cystic carcinoma. |
Graef J [35] | 2023 | High-grade glioma | 3 | Two cycles; median activity of 6.03 GBq (IQR 5.74–6.10) | In high-grade glioma, a minority of patients were eligible for PSMA-RLT, and the tumour dose was too low for a sufficient therapeutic effect. |
Truckenmueller P [36] | 2022 | High-grade glioma | 3 | Two cycles; median activity of 6.03 GBq (5.74–6.10); time interval 9–11 weeks | Only a minor proportion of the patients were eligible for PSMA-RLT based on the TBRmax threshold. |
Hirmas N [37] | 2021 | Hepatocellular carcinoma | 2 | One cycle; 5.9–6.2 GBq | PSMA-RLT was not effective since it did not yield a sufficient tumour radiation dose. |
Wächter S [40] | 2021 | Anaplastic and poorly differentiated thyroid carcinoma | 1 | Two cycles, 6.3 GBq e 7.4 GBq, time interval 8 weeks | PSMA-targeted therapy could be used as an alternative option in selected patients if they showed progression after established therapeutic lines. |
de Vries LH [41] | 2020 | Radioactive iodine-refractory differentiated thyroid cancer | 2 | Two cycles; 6 GBq, time interval 6 and 11 weeks | PSMA-RLT showed a modest, temporary response. |
Digklia A [42] | 2022 | Uterine leiomyosarcoma | 1 | Two cycles (2 months apart) combined with 240 mg of nivolumab (every 2 weeks) | At 6 months post-treatment, a reduction in the tumor growth rate (TGR (%/month) from 36.46%/m to 11.25%/m was shown. |
Jüptner [43] | 2019 | Vena cava leiomyosarcoma | 1 | One cycle, 6 GBq | Treatment was well tolerated. However, because of the week retention of the radiotracer, the therapy was discontinued, and no further treatment cycles were arranged. |
Simsek [44] | 2021 | Testicular mixed germ cell tumour | 1 | One cycle, 7.5 GBq | Treatment was well tolerated without any adverse effects. However, the disease progressed. |
3.3. Ongoing Clinical Trials
Type of Cancer | Centre/Sponsor | Patients | Study Phase | Trial ID (Reference) | Status |
---|---|---|---|---|---|
Adenoid cystic carcinoma | Peking Union Medical College Hospital, Beijing, China | 40 | Early Phase I | NCT04801264 | Unknown |
Renal cell carcinoma | Peking Union Medical College Hospital, Beijing, China | 40 | Not Applicable | NCT05170555 | Unknown |
Salivary gland cancer | Radboud University Medical Center, Nijmegen, Gelderland, Netherlands | 12 | Phase II | NCT04291300 | Completed |
PSMA-positive tumours | Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Cesena, Italy | 100 | Phase II | NCT05867615 | Recruiting |
High-grade glioma | St. Olavs Hospital, Trondheim, Norway | 10 | Not Applicable | NCT05644080 | Recruiting |
Soft tissue sarcoma | University of Lausanne Hospitals, Lausanne, Vaud, Switzerland | 20 | Phase I | NCT05420727 | Recruiting |
Metastatic clear cell renal cancer | Centre Leon Berard, Lyon, France | 48 | Phase I/II | NCT06059014 | Recruiting |
4. Discussion and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Dondi, F.; Miceli, A.; Rovera, G.; Feudo, V.; Battisti, C.; Rondini, M.; Marongiu, A.; Mura, A.; Camedda, R.; De Feo, M.S.; et al. Prostate-Specific Membrane Antigen Radioligand Therapy in Non-Prostate Cancers: Where Do We Stand? Bioengineering 2024, 11, 714. https://doi.org/10.3390/bioengineering11070714
Dondi F, Miceli A, Rovera G, Feudo V, Battisti C, Rondini M, Marongiu A, Mura A, Camedda R, De Feo MS, et al. Prostate-Specific Membrane Antigen Radioligand Therapy in Non-Prostate Cancers: Where Do We Stand? Bioengineering. 2024; 11(7):714. https://doi.org/10.3390/bioengineering11070714
Chicago/Turabian StyleDondi, Francesco, Alberto Miceli, Guido Rovera, Vanessa Feudo, Claudia Battisti, Maria Rondini, Andrea Marongiu, Antonio Mura, Riccardo Camedda, Maria Silvia De Feo, and et al. 2024. "Prostate-Specific Membrane Antigen Radioligand Therapy in Non-Prostate Cancers: Where Do We Stand?" Bioengineering 11, no. 7: 714. https://doi.org/10.3390/bioengineering11070714