Search Results (662)

Background: Although fentanyl significantly contributes to opioid-related morbidity and mortality, little is known about the epigenetic changes that may influence long-term neuronal adaptations. Objective: The effects of repeated fentanyl administration on class IIa histone deacetylase (HDAC) expression-activity were studied using the radiotracer [¹⁸F]TFAHA and positron emission tomography (PET) imaging in a model of fentanyl-induced behavioral sensitization. Methods: Female and male Wistar rats received 14 days of fentanyl (20 μg/kg) or saline injections and a 14-day drug-free period followed by a single fentanyl or saline challenge dose on day 28. Locomotor activity (LMA) was measured on days 0, 1, 14, and 28 with PET imaging being performed at baseline and again on day 28 following the fentanyl/saline challenge and LMA. The percent change in standard uptake value (body weight corrected) between pre- and post-administration was calculated as a measure of class IIa HDAC expression-activity. Results: Repeated fentanyl exposure resulted in significantly increased LMA in both sexes compared to controls. Females displayed an earlier onset (day 1) and a greater magnitude of behavioral sensitization on days 14 and 28 compared to males. Fentanyl significantly decreased class IIa HDAC expression-activity across time in the whole brain and in reward-related brain regions without sex differences. Conclusions: Prolonged fentanyl exposure induces robust sex-specific locomotor sensitization with varying magnitude over time, suggesting differential neuroadaptive processes. Fentanyl also appears to induce epigenetic changes in the brain independent of sex and region. The effect of fentanyl on class II HDACs may not directly impact the expression of behavioral sensitization. Full article

Lymph node involvement in prostate cancer has major prognostic and therapeutic implications, yet conventional imaging based on size and morphology remains limited in detecting small-volume metastatic disease. Although extended pelvic lymph node dissection is considered the reference standard for nodal staging, it is invasive, associated with morbidity, and primarily diagnostic in intent. Prostate-specific membrane antigen positron emission tomography (PSMA PET) has reshaped staging by enabling molecular detection of nodal metastases, consistently demonstrating superior accuracy compared with conventional imaging. This narrative review critically evaluates the role of PSMA PET in lymph node staging, with a primary focus on primary diagnosis and selected considerations on biochemical recurrence, focusing not only on diagnostic accuracy but on clinical utility and decision-making. PSMA PET shows high specificity but moderate sensitivity for pelvic nodal metastases, with reduced performance for micrometastatic disease; therefore, a negative scan cannot reliably exclude nodal involvement in high-risk patients. Evidence indicates frequent stage migration and management changes, including refinement of surgical planning, radiotherapy target delineation, and treatment intensification strategies. However, most pivotal therapeutic trials were based on conventional imaging, and long-term outcome data validating PSMA PET-guided treatment adaptations remain limited. We discuss biological rationale, radiotracer characteristics, interpretation frameworks, guideline perspectives, real-world variability in adoption, and current limitations, including false-positive findings, PSMA heterogeneity, and lack of universal standardization. Rather than replacing established staging paradigms, PSMA PET should be integrated within a comprehensive, risk-adapted framework. Ongoing prospective trials will clarify whether molecularly defined nodal staging translates into improved oncologic outcomes and will determine its definitive role in contemporary prostate cancer management. Full article

Incorporation of carbon-11 radiotracers for positron emission tomography (PET) imaging requires close coordination between cyclotron operation, radiochemistry production, quality control, and clinical administration. A persistent challenge exists is the minimization of the carbon-12 isotopologue mass of the radiotracer, which reduces molar activity and can compromise PET image quality. This challenge can be particularly acute at facilities where cyclotron operation and carbon-11 radiochemistry are realized by separate organizations with distinct operational priorities. Here, we describe how the Radiochemistry Group at New York University Grossman School of Medicine and Siemens Healthineers have developed an integrated operational framework for consistent, high-quality carbon-11 production within an academic–industry partnership. Cyclotron target maintenance and conditioning protocols, remote chemistry module maintenance schedules, a validated radio-HPLC method (UV LOD = 0.9 µg/mL, UV LOQ = 3.0 µg/mL) for trending methyl iodide isotopologue mass, and structured inter-team communication protocols are presented in this manuscript. Quality analysis demonstrates molar activities consistently exceeding the recommended minimum of 40 GBq/µmol for reversibly binding radiotracers used in human PET studies. This work is intended as a practical resource for radiochemists, cyclotron engineers, and facility managers working to establish or improve institutional carbon-11 programs. Full article

99mTc-pyrophosphate (PYP) scintigraphy is widely used for the noninvasive evaluation of transthyretin cardiac amyloidosis. Although interpretation primarily focuses on myocardial uptake, confirmation of appropriate systemic radiotracer biodistribution is essential. We report a case in which an examination presumed to be 99mTc-PYP scintigraphy demonstrated free 99mTc-pertechnetate-like biodistribution. A 75-year-old woman with chronic kidney disease and conduction disturbance underwent 99mTc-PYP scintigraphy for suspected cardiac amyloidosis. The initial study, recorded as the administration of 740 MBq 99mTc-PYP, was imaged 3 h after injection. Planar imaging showed mild apparent activity over the cardiac region; however, SPECT/CT demonstrated no definite myocardial uptake. Instead, intense uptake was observed in the stomach and thyroid gland, with complete absence of skeletal activity. This distribution was inconsistent with correctly administered 99mTc-PYP and suggested free 99mTc-pertechnetate biodistribution, likely due to radiopharmaceutical preparation or administration error. A repeat 99mTc-PYP scan 1.5 months later showed expected skeletal uptake without gastric or thyroid activity and again demonstrated no myocardial uptake. The study was interpreted as negative for cardiac amyloidosis. Gastric and thyroid uptake with absent skeletal activity on presumed 99mTc-PYP scintigraphy should be considered nondiagnostic rather than negative. Full article

Background: Positron emission tomography (PET) is a molecular imaging technique that exploits the β⁺ decay of selected radionuclides to enable non-invasive in vivo investigation of biochemical and physiological processes, including early and subclinical disease alterations. Radiotracers are designed to bind specific molecular targets with high affinity and selectivity. Among the targets to which PET devotes increasing attention are G protein-coupled receptors (GPCRs)—the largest class of transmembrane receptors—which orchestrate a wide spectrum of biological outcomes and are widely implicated in human disease. Objectives: This review analyzes patents published between 2020 and 2025 focusing on GPCR-targeted PET radiotracers, highlighting design strategies, radionuclide selection, and translational perspectives across oncology, central nervous system (CNS) disorders, and inflammatory diseases. Results: Patent activity shows that most GPCR-targeted PET tracers are derived from validated ligands adapted for imaging while preserving affinity and selectivity. Oncology patents mainly favor peptide-based or modular metal–chelator platforms enabling radionuclide flexibility and theranostic extension, whereas CNS tracers rely on drug-like small molecules optimized under strict ADME and blood–brain barrier constraints. Increasing emphasis on non-orthosteric, function-sensitive, and dual-targeting approaches reflects a shift toward interrogating GPCR signaling states, while inflammatory indications remain comparatively underrepresented despite clear biological foundations. Conclusions: Current patent trends consolidate GPCR-targeted PET tracers as well-established diagnostic tools while progressively expanding their clinical utility, both as platforms supporting translational research—informing mechanistic insight and drug development—and as components of emerging theranostic strategies across multiple disease areas. Full article

Dicarbadodecaboranes (12) (carboranes) are versatile molecular building blocks with unique properties, which allow the expansion of classical medicinal-chemical space. To enable single-photon emission computed tomography (SPECT) imaging of cyclooxygenase-2 (COX-2), we investigated the feasibility of introducing iodine-123 into nido-indoborin 1, a nido-carborane analog of indomethacin with potent and selective cyclooxygenase-2 inhibitory activity. An electrophilic iodination strategy afforded two regioisomers, 2a and 2b, bearing the iodine at the carborane cluster. Compared to nido-indoborin, a reduced COX-2 inhibition potency and selectivity were observed, with 2b exhibiting the more favorable inhibition profile. Radiosynthesis of [¹²³I]2b was achieved by N-chlorosuccinimide–mediated electrophilic substitution of 1, and conditions were optimized, leading to an isolated radiochemical yield of 4%. While the radiotracer displayed high stability in phosphate buffer, ester hydrolysis was observed in human plasma and murine liver microsomes with no significant deiodination in vitro. Cell uptake studies indicated partial COX-2–dependent accumulation but also revealed substantial non-specific uptake and unexpected enhancement of radiotracer uptake in the presence of carborane-based blocking agents. In vivo pilot imaging studies in mice bearing U87 xenografts showed renal and hepatobiliary clearance without measurable tumor accumulation but evidence of deiodination over time. Overall, iodination was feasible, but the resulting compounds lacked the required COX-2-selective tumor accumulation for further radiotracer development. Full article

Copper-64 is increasingly recognized for its advantages in positron emission tomography (PET) imaging and theranostic applications due to its favorable half-life, decay profile, and high spatial resolution. This research addresses the need for reliable, high-purity PET radiotracers by developing GMP-grade lyophilized kits for one-step preparation of ⁶⁴Cu-NOTA-peptides using gelatin as a chelating agent for metallic impurities and NOTA for selective copper binding. The approach was applied to five peptide analogs formulated for fast ⁶⁴Cu labeling: NOTA-iPSMA, NOTA-TOC, NOTA-iPD-L1, NOTA-iFAP, and NOTA-UBI 29–41, which were preclinically evaluated to enable the precise molecular imaging of cancer and infection. Each multidose kit included 0.5 μmol of the NOTA-peptide and 25 mg of gelatin, labeled with 925 MBq of ⁶⁴Cu. The radiochemical purity of the ⁶⁴Cu-NOTA-peptides exceeded 98% (mean 99.2% ± 0.3%) without the need for additional purification. The ⁶⁴Cu-radiotracers remained stable for at least 24 h at room temperature and showed high stability in human serum. In preclinical studies, saturation-binding assays demonstrated that affinity (Kd) was less than 10 nM in all ⁶⁴Cu-NOTA-peptides, with tumor-to-lung ratios ranging from 14 to 290 at 2 h post-injection and low liver uptake (2.95% ± 1.36% ID/g). The research demonstrated that these formulations, which include peptides specific to PSMA, SSTR2, PD-L1, FAP, and infection sites, offer excellent in vivo performance and high PET imaging quality in mice with induced tumors or infection sites. The findings support the use of gelatin-NOTA-peptide kits as a standardized and practical solution for producing ⁶⁴Cu-labeled peptides, facilitating routine clinical PET imaging, and advancing personalized molecular diagnostics. Full article

Fluorine-18 is often considered an ideal positron emitter owing to its excellent chemical, physiological, and nuclear properties. Consequently, the development of rapid, simple, and reliable ¹⁸F-labeling strategies remains critically important for synthesizing new radiopharmaceuticals for PET molecular imaging. A common approach involves the synthesis of ¹⁸F-labeled prosthetic groups that subsequently undergo bioconjugation with peptides or other biomolecules to generate ¹⁸F-labeled imaging probes. However, conventional synthetic methods for these prosthetic groups are often lengthy, require large quantities of precursor and solvent, and typically rely on elevated reaction temperatures. Herein, we report a droplet-based microscale synthetic methodology for the preparation of the [¹⁸F]FVSB prosthetic group that minimizes precursor and solvent usage, proceeds rapidly, and operates at relatively low temperatures. Conditions were optimized using a platform for performing droplet reactions in parallel, enabling high-throughput study of multiple reaction parameters within a short period of time. Additionally, we introduce a simple micro-cartridge purification technique that affords purified [¹⁸F]FVSB in small volumes. Furthermore, we describe an efficient bioconjugation that requires substantially lower reagent amounts than the previously reported macroscale method. The microscale process we report could facilitate wider use of this ¹⁸F-labeling strategy and can be extended to label other thiol-bearing peptides or biomolecules. Full article

Pharmacokinetic modeling in Positron Emission Tomography (PET) imaging has become a cornerstone in cancer research, offering insights into tumor development and progression. These models facilitate the quantification of radiotracer distribution and metabolism, enabling precise measurement of physiological parameters essential for cancer diagnosis, staging, and treatment monitoring. However, accurate pharmacokinetic modeling depends on reliable input function acquisition and partial volume correction techniques to minimize biases in quantitative PET metrics. This review provides a comprehensive overview of current methodologies and advancements in pharmacokinetic modeling for PET oncology imaging. We discuss techniques for acquiring input functions, including arterial, venous, and image-derived input functions (IDIFs), along with population-based input functions (PBIFs). Their strengths, limitations, and clinical applications are critically evaluated. Additionally, we examine quantitative methods such as partial volume correction (PVC) that mitigate the spatial resolution limitations of PET, improving radiotracer quantification in small or heterogeneous tumors. Furthermore, we explore advanced kinetic modeling techniques, including compartmental models, graphical approaches, and data-driven methods, highlighting recent innovations such as machine learning and Bayesian modeling. Key areas for future research in PET pharmacokinetic modeling include integrating hybrid imaging modalities, developing robust patient-specific input functions, and leveraging machine learning to streamline modeling processes. These advancements aim to enhance the precision and clinical utility of PET imaging in oncology, leading to more personalized cancer treatment strategies. Full article

Rapid sterility testing of radiopharmaceuticals is essential due to their short half-lives and strict safety requirements. Conventional culture-based methods require several days and are not compatible with clinical workflows. In this work, we present a proof-of-concept droplet-based microfluidic platform for rapid optical detection of bacterial contamination through optical extinction analysis of microdroplets. Monodisperse water-in-oil microdroplets were generated and optically interrogated using a fiber-based detection system. Calibration was first performed using 500 nm polystyrene nanoparticles to establish the relationship between particle concentration and optical extinction. Subsequently, Staphylococcus aureus suspensions were analyzed under aerobic and anaerobic conditions at concentrations ranging from 0 to 230 CFU/mL. The system demonstrated reliable detection of bacterial contamination with estimated limits of detection of ~15 CFU/mL (aerobic) and ~7.5 CFU/mL (anaerobic). The platform enables real-time, high-throughput analysis with minimal sample handling and reduced analysis time compared to conventional sterility tests. This study validates the feasibility of microdroplet-based optical detection as a rapid quality control strategy specifically suited for radiopharmaceutical production, where the short half-lives of common radiotracers impose strict time constraints incompatible with conventional 14-day culture-based sterility tests. The results provide a proof-of-concept foundation for future integration into automated sterility testing workflows, with further validation on real radiopharmaceutical matrices planned as the next step. Full article

Background/Objectives: Fibroblast activation protein (FAP) has emerged as a promising target for oncologic molecular imaging due to its high expression in cancer-associated fibroblasts and low presence in healthy tissues. Among available FAP ligands, [⁶⁸Ga]Ga-FAPi-46 has shown rapid tumor accumulation, low background uptake, and broad tumor applicability. This study reports the successful translation of [⁶⁸Ga]Ga-FAPi-46 from preclinical development to routine clinical radiopharmacy practice, detailing automated synthesis, quality control performance, radiochemical stability, and the first clinical imaging results. Methods: Automated radiolabeling of FAPi-46 with gallium-68 was performed using a synthesis module. Quality control included radiochemical purity assessments by iTLC, SPE, and RP-HPLC (pH, appearance, endotoxin levels, and membrane integrity testing). Radiochemical stability was evaluated in saline (up to 6 h) and human serum (up to 90 min). In vitro characterization included the partition coefficient and serum protein binding determination. A clinical evaluation was conducted in a woman with newly diagnosed lung adenocarcinoma who underwent both [¹⁸F]FDG PET/CT and [⁶⁸Ga]Ga-FAPi-46 PET/CT. Results: Automated synthesis of [⁶⁸Ga]Ga-FAPi-46 achieved a high radiochemical yield (87.9 ± 1.3%) and radiochemical purity greater than 98%. All batches met release specifications for sterility, apyrogenicity, and physicochemical parameters. The radiotracer demonstrated high stability in saline and human serum, with radiochemical purity consistently above 95% at all evaluated time points. The compound showed a hydrophilic profile (LogP = −3.32 ± 0.14) and 40–60% serum protein binding. Clinically, [⁶⁸Ga]Ga-FAPi-46 PET/CT provided superior lesion delineation compared to [¹⁸F]FDG, revealing additional mediastinal, supraclavicular, and brain metastases. Conclusions: [⁶⁸Ga]Ga-FAPi-46 can be reliably synthesized using automated procedures under routine radiopharmacy conditions, meeting regulatory quality standards and demonstrating excellent stability. Its enhanced lesion detectability compared with [¹⁸F]FDG in the first patient case supports its potential value for oncological staging and clinical implementation. Full article

Background and Objectives: Bladder cancer is one of the most common malignancies of the urinary tract and poses a significant clinical challenge due to its biological heterogeneity and high rates of recurrence and progression. Urothelial carcinoma represents the predominant histological subtype, ranging from non-muscle-invasive disease with relatively favorable outcomes to aggressive muscle-invasive and metastatic forms associated with poor prognosis. Accurate diagnosis, staging, prognostic stratification, and assessment of treatment response are therefore essential for optimal patient management. The objective of this review is to summarize and critically evaluate the current evidence on the role of positron emission tomography/computed tomography (PET/CT) in bladder cancer, with particular emphasis on [¹⁸F]FDG PET/CT and non-FDG radiotracers. Materials and Methods: A narrative review of the available literature was performed, focusing on clinical studies, review articles, and guideline documents addressing the use of PET/CT in bladder cancer. The literature search included articles published between 2000 and 2025, while earlier landmark studies were selectively included if considered historically important for understanding the development of PET/CT imaging in bladder cancer. The initial search yielded over 500 records; after screening titles and abstracts, more than 100 articles were selected for full-text evaluation. The analyzed evidence encompasses the clinical applications of [¹⁸F]FDG PET/CT and alternative radiotracers, including choline-, acetate-, methionine-, and sodium fluoride-based tracers, and fibroblast activation protein inhibitors (FAPI), across different stages of disease and clinical settings. Results: Conventional imaging modalities, such as computed tomography and magnetic resonance imaging, provide important anatomical information but remain limited in the evaluation of lymph node involvement, early metastatic disease, treatment response, and disease recurrence. Despite limitations related to physiological urinary excretion, [¹⁸F]FDG PET/CT has demonstrated clinical value in selected scenarios, particularly for staging, prognostic assessment, detection of recurrence, and response evaluation. To overcome FDG-related constraints, several non-FDG radiotracers have been investigated. Among these, FAPI PET/CT has emerged as a promising modality due to its ability to target the tumor stroma, potentially improving lesion detectability and tumor-to-background contrast. Conclusions: This review summarizes and critically evaluates current evidence on the role of PET/CT in bladder cancer, with a focus on [¹⁸F]FDG PET/CT and non-FDG radiotracers. The discussed studies highlight their applications in primary diagnosis, staging, prognostic assessment, detection of recurrence, and evaluation of treatment response, as well as their respective advantages and limitations. Furthermore, potential future directions for PET/CT imaging in clinical practice are outlined, emphasizing the need for further research to clarify the optimal use of established and emerging radiotracers. Full article

Background/Objectives: The F3 peptide, a tumor-homing peptide known to bind cell-surface nucleolin, is frequently employed as a targeting vector in cancer research. However, the impact of the modification site on its cellular binding properties has not been investigated yet. In this work, we aimed to design an improved F3-based radioconjugate by identifying the optimal conjugation site and establishing a protocol for its biological evaluation in vitro. To achieve this, we compared F3 peptide derivatives modified at their N- or C-termini with DOTA for complexation of indium-111 (¹¹¹In) for SPECT or Auger electron therapy or a fluorophore (FITC) for optical imaging. Methods: N-and C-terminal DOTA-modified F3 peptides were radiolabeled with indium-111 and compared for their in vitro stability in different physiologically relevant media. Suitable nucleolin-positive cell lines for further in vitro studies were identified by confocal microscopy of a FITC-labeled F3 peptide derivative. The radioconjugates were then investigated on MDA-MB-231 (breast cancer) and PC-3 (prostate cancer) cells for nucleolin-specific cell binding and uptake, and several parameters of the in vitro assays were varied to establish a suitable protocol. Results: In general, in vitro assays with F3 peptide conjugates are challenging, as the outcome depends on a number of experimental parameters, leading, in some cases, to varying results. In particular, the presence of Ca²⁺ and Mg²⁺ had a decisive impact on the results, likely because the metal ions compete with the binding of F3 conjugates to nucleolin. The C-terminal modified, ¹¹¹In-labeled F3 radioconjugate performed better than the N-terminal modified analog. While several parameters of the in vitro experiments were optimized, the overall cell uptake in vitro of radioactivity was still low (<2% of applied radioactivity). Conclusions: A standardized in vitro protocol for evaluating F3 peptide conjugates on cancer cells was established, revealing that the C-terminus is the preferred site for modification. Because the cellular uptake of the radiotracer was shown to likely not be sufficient for radiotracer development, further studies on the optimization of the F3 peptide conjugates, including structural modifications, are required. Full article

Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU/kg), Vitamin D (60,000 IU/kg), Doxorubicin, DOX + Vitamin D (5000 IU/kg), and DOX + Vitamin D (60,000 IU/kg). Vitamin D₃ (cholecalciferol) was administered orally either as a daily dose (5000 IU/kg for 12 days) or as a single bolus dose (60,000 IU/kg). Doxorubicin (6 mg/kg/day, cumulative dose 18 mg/kg) was administered intraperitoneally on days 10–12. Hepatic injury was evaluated using ⁹⁹mTc-pyrophosphate (⁹⁹mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10). Results: Doxorubicin markedly increased hepatic ⁹⁹mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-α, IL-6, and IL-1β levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p < 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 ± 2.7 vs. 74.1 ± 3.8 and 69.3 ± 3.2 ng/mL for the 5000 and 60,000 IU/kg groups, respectively; p < 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, ⁹⁹mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses. Full article