The phase 2 ARROW study was designed to evaluate radioligand therapy with 131I-LNTH-1095, an iodine-131-labeled small molecule targeting PSMA, in combination with enzalutamide in subjects with metastatic castration-resistant prostate cancer after progression on prior abiraterone therapy. Men ≥18 years with PSMA-positive prostate cancer (PSMA PET tracer uptake >1× liver SUVmean in all CT-measurable lesions) were randomized 2:1 to 131I-LNTH-1095 (4 cycles of 3.7 GBq/dose every 8 weeks)+enzalutamide (160 mg po qd) vs. enzalutamide alone. The primary endpoint was PSA50 response. Secondary endpoints included rPFS, ORR, OS, and safety. Of 177 screened subjects, 120 were randomized (80: 131I-LNTH-1095+enzalutamide; 40: enzalutamide-monotherapy). PSA50 response was 62.9% (95% CI, 50.5-74.1) for 131I-LNTH-1095+enzalutamide vs. 31.3% (16.1-50.0) for enzalutamide alone (P=.003). Median rPFS was 14.0 months (95% CI: 8.64-18.20) for 131I-LNTH-1095+enzalutamide vs. 11.5 months (2.79-18.43) for enzalutamide alone (P=.10). Incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was 65.8% for 131I-095+enzalutamide vs. 41.0% for enzalutamide-monotherapy; the most frequent TEAEs were fatigue (75.0 vs. 53.8%), nausea (59.2 vs. 33.3%), thrombocytopenia (51.3 vs. 0%), and decreased appetite (48.7 vs. 17.9%), respectively. Two deaths in the 131I-LNTH-1095+enzalutamide group were considered treatment-related. The study was not powered to detect rPFS and OS differences. 131I-LNTH-1095+enzalutamide was associated with a statistically significant improvement in PSA50 response compared to enzalutamide alone despite a lower dosing schedule (4 cycles of 3.7 GBq/dose every 8 weeks) than the other approved PSMA RLT agents. Grade ≥3 adverse events were more frequent with combination therapy, particularly hematologic toxicity. NCT03939689.

A progressive decline in mitochondrial oxidative phosphorylation (OxPhos) is a fundamental feature of aging and a strong predictor of mobility loss, cognitive decline, and dementia. (1-4) Work from the Baltimore Longitudinal Study of Aging and complementary cohorts demonstrates that reduced skeletal muscle mitochondrial OxPhos, assessed in vivo by ^31P-MRS, precedes and predicts deterioration in walking performance, cardiorespiratory fitness, brain structural integrity, and risk of mild cognitive impairment and dementia. These associations suggest that mitochondrial dysfunction represents a shared biological mechanism underlying both physical and cognitive aging. This project focuses on cardiolipin, a signature phospholipid of the mitochondrial inner membrane that is essential for respiratory chain supercomplex assembly, proton handling, and efficient ATP synthesis. Cardiolipin is highly susceptible to oxidative damage, and emerging evidence indicates that oxidized cardiolipin is poorly repaired, promotes inflammation and apoptosis, and compromises mitochondrial quality control. We hypothesize that aging is characterized by the accumulation of oxidized cardiolipin due to impaired remodeling and insufficient availability of key lipid precursors, particularly lysophosphatidylcholine species containing oleic (18:1) and linoleic (18:2) acids. To test this hypothesis, we integrate longitudinal human phenotyping with advanced metabolomics, lipidomics, and “in vivo” imaging. We have identified lipid metabolites linking mitochondrial OxPhos to mobility and cognition and developed a highly sensitive method to quantify native and oxidized cardiolipin species in human skeletal muscle. Preliminary data indicate that higher levels of tetralinoleoyl cardiolipin are associated with better physical and cognitive performance, whereas a greater proportion of oxidized cardiolipin predicts worse outcomes. Ongoing efforts aim to extend these findings to the brain using novel PET radioligands and advanced MRS techniques. Together, this work positions cardiolipin remodeling and mitochondrial quality control as central mechanisms of aging and promising targets for interventions to preserve physical and cognitive function in late life.

Comparative study of 47Sc and 177Lu-labeled albumin binder-conjugated FAPI radiopharmaceuticals.

H3RESCA chelator-enabled [18F]AlF labeling: An optimized temperature-resilient platform for PSMA-targeted PET tracers in prostate cancer.

Preclinical studies have demonstrated that [68Ga]Ga/[177Lu]Lu-DOTA-NI-FAPI-04, a bivalent agent containing an extra hypoxia-sensitive 2-nitroimidazole (NI) group, exhibited favorable tumor binding affinity and improved tumor uptake and retention than [68Ga]Ga/[177Lu]Lu-DOTA-FAPI-04. This study aims to further investigate the value of clinical application for [68Ga]Ga-DOTA-NI-FAPI-04 PET/CT via a direct head-to-head comparison with [68Ga]Ga-DOTA-FAPI-04. A total of 50 patients underwent paired [68Ga]Ga-DOTA-NI-FAPI-04 and [68Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week interval. Among these, four patients underwent serial dynamic [68Ga]Ga-DOTA-NI-FAPI-04 PET scans for dosimetry evaluation, and the others underwent scans at 60min and 120min. Additionally, we calculated the SUVmax differences (ΔSUVmax) by [68Ga]Ga-DOTA-NI-FAPI-04 minus [68Ga]Ga-DOTA-FAPI-04 PET/CT for further analysis. Immunohistochemistry for FAP and hypoxia-inducible factor-1 alpha (HIF-1α) was performed in 22 primary tumors. The effective absorbed dose of [68Ga]Ga-DOTA-NI-FAPI-04 PET/CT was calculated as 1.95E-02 mSv/MBq. Tumor uptake of [68Ga]Ga-DOTA-NI-FAPI-04 showed rapid uptake and steady values (average SUVmax 11.6-13.0 from 3 to 120min). [68Ga]Ga-DOTA-NI-FAPI-04 exhibited significantly higher uptake in tumor lesions compared to [68Ga]Ga-DOTA-FAPI-04 PET/CT, particularly in primary tumors (P < 0.05), nodal metastases (P < 0.001), bone metastases (P < 0.001), and liver metastases (P < 0.05). That of FAP expression was correlated with that of HIF-1α (r = 0.661, P < 0.001), and the expression of HIF-1α showed a positive correlation with ΔSUVmax (r = 0.528, P = 0.011). [68Ga]Ga-DOTA-NI-FAPI-04 showed significantly higher tumor uptake and retention over [68Ga]Ga-DOTA-FAPI-04, with particularly enhanced visualization of hypoxic lesions, suggesting that hypoxia-sensitive moiety may play an important role in detection of tumors. Further study of [177Lu]Lu-DOTA-NI-FAPI-04 in humans is warranted to explore its clinical applications. URL OF REGISTRY: https://clinicaltrials.gov/study/NCT06688305 . ClinicalTrials.gov, NCT06688305, Registered 14 November 2024, retrospectively registered.

Preclinical evaluation of 68Ga-labeled acetazolamide derivatives as radiotracers targeting carbonic anhydrase IX in clear cell renal cell carcinoma.

Huntington's disease (HD) is a progressive neurodegenerative disorder in which neuroinflammation, oxidative stress, and mitochondrial dysfunction are increasingly recognized as important contributors to neuronal vulnerability. Recent evidence indicates that the ATP-gated P2X7 receptor (P2X7R) may participate in coordinating several of these pathological processes. Under conditions of cellular stress, elevated extracellular ATP can promote sustained activation of P2X7R, leading to Ca2⁺ influx, mitochondrial depolarization, and enhanced production of reactive oxygen species (ROS), in part through NADPH oxidase-dependent mechanisms. This oxidative environment is associated with lipid peroxidation and the generation of electrophilic aldehydes, such as 4-hydroxynonenal and malondialdehyde, which have the potential to influence chromatin organization and disrupt histone modifications, thereby contributing to altered transcriptional regulation. In parallel, activation of P2X7R in microglia has been linked to NLRP3 inflammasome activation and the release of pro-inflammatory cytokines, including IL-1β and IL-18, which may further exacerbate neuroinflammatory signaling. Together, these observations support the hypothesis of a P2X7-redox-lipid-epigenetic axis that could contribute to neuronal susceptibility and striatal pathology in HD. Preclinical studies suggest that inhibition of P2X7R can attenuate neuroinflammation, improve mitochondrial function, and partially ameliorate behavioral deficits in experimental models. In addition, the development of brain-penetrant P2X7R antagonists and P2X7-specific PET tracers provides emerging opportunities for translational research, biomarker development, and therapeutic monitoring. Overall, P2X7R represents a promising, though still exploratory, therapeutic target in HD.

Longitudinal comparison of adaptive neuroplasticity in two rat models of unilateral vestibulopathy by dual-tracer [18F]FDG and [18F]UCB-H PET.

CD105 (endoglin) is a proliferation-associated transmembrane glycoprotein selectively expressed on activated endothelial cells in tumor neovasculature and serves as an attractive biomarker for imaging tumor angiogenesis. Here, we report the development of a novel CD105-targeted PET tracer, 68Ga-DOTA-CDP, based on a high-affinity peptide (KD = 13.5 nM) identified from a combinatorial library. The radiotracer was obtained with high radiochemical purity (>97%), excellent stability in phosphate-buffered saline and fetal bovine serum, and favorable hydrophilicity. In vitro confocal imaging and flow cytometry demonstrated specific binding of CDP to CD105-positive HUVECs with minimal uptake in CD105-negative cells. Micro-PET imaging in multiple tumor-bearing mouse models, including 4T1, A549, H1975, MDA-MB-231, and JIMT-1 xenografts, enabled rapid tumor visualization at early time points following injection. Tracer uptake was significantly higher in CD105-high tumors compared with CD105-low tumors, with the highest accumulation observed in the triple-negative breast cancer model MDA-MB-231. Biodistribution studies revealed predominant renal clearance, low hepatic uptake, and favorable tumor-to-background ratios. Blocking experiments with excess unlabeled peptide markedly reduced tumor uptake, confirming receptor-mediated targeting. Immunohistochemical analysis further validated heterogeneous CD105 expression in tumor neovasculature and demonstrated a positive correlation between CD105 expression levels and PET-derived tumor uptake. Overall, 68Ga-DOTA-CDP shows promise as a peptide-based PET tracer for noninvasive tumor angiogenesis imaging.

Gastrin-releasing peptide receptor (GRPR) attracts increasing attention as a target for radiotheranostic applications. We previously developed a metabolically stable GRPR-targeting peptide, incorporating α-methyl-L-tryptophan within its sequence (PEG2-Pip-D-Phe6-Gln7-MetTrp8-Ala9-Val10-Sar11-His12-Sta13-Leu14-NH2) and coupled it to DOTAGA chelator (PKB2) and to DOTA (PKB3). When labelled with Lu-177, both peptide variants demonstrated promising properties for targeted radionuclide therapy. In this study, we aimed to evaluate the diagnostic counterparts of PKB2 and PKB3 by radiolabelling them with Ga-68 for positron emission tomography (PET) imaging. [68Ga]Ga-PKB2 and [68Ga]Ga-PKB3 were produced with radiochemical yields over 99% and radiochemical purities over 97%. Both radiopeptides showed a high GRPR affinity with IC50 values in the low nanomolar range and a GRPR-mediated uptake in PC-3 cells with slow internalization. The labelled peptides [68Ga]Ga-PKB2 and [68Ga]Ga-PKB3 demonstrated fast clearance with activity concentration in blood below 0.5%IA/g at 2pi, and a high tumour activity uptake in PC-3 xenografts (16 ± 3%IA/g and 17 ± 2%IA/g, respectively). [68Ga]Ga-PKB3 had a significantly higher activity uptake in the pancreas (GRPR-expressing organ) and lower uptake in the kidneys than [68Ga]Ga-PKB2. PET/CT images were concordant with the biodistribution results, clearly delineating tumour tissue. [68Ga]Ga-PKB2 and [68Ga]Ga-PKB3 are promising PET tracers for imaging of GRPR-positive tumours and are potential diagnostic counterparts to their 177Lu-labelled analogues, supporting their use as a 177Lu/68Ga theranostic pair.

Meningiomas account for 41.7% of primary central nervous system (CNS) tumors and overexpress somatostatin receptor 2 (SSTR2) receptors, enabling superior tumor-to-background contrast compared with MRI and computed tomography imaging, which have limited ability to distinguish neoplastic tissue from normal dural enhancement. This review aimed to evaluate SSTR-targeted PET radiotracers for diagnosis, treatment planning, surveillance, and theranostic applications in meningioma management. Literature review of PubMed, Google Scholar, Embase, and Web of Science databases from inception to November 2025. Studies evaluating [68Ga]Ga-DOTATATE, [68Ga]Ga-DOTATOC, [68Ga]Ga-DOTANOC, and novel fluorine-18 tracers in meningioma patients were analyzed. SSTR-PET demonstrated superior diagnostic sensitivity (95-100%) with 10-fold higher SSTR2-binding affinity than conventional scintigraphy. Osseous involvement detection exceeded MRI (98.5 vs. 53.7%; n = 82). PET-guided radiation planning reduced target volumes by 84% (71.39 → 11.12 cm3; P < 0.05) while decreasing critical structure exposure by greater than or equal to 50%. Posttreatment surveillance detected residual tumor in 41-63% of patients deemed completely resected by Simpson grading and MRI (n = 37). SSTR-PET altered management in 42% of cases by identifying occult disease. The theranostic paradigm using [177Lu]Lu-DOTATATE achieved 60-80% disease stabilization in recurrent/progressive cases. Next-generation [18F]SiTATE tracers offer improved logistics and cost-effectiveness. Technical heterogeneity in acquisition protocols and lack of standardized uptake value thresholds (range: 2.3->4.0) limit generalizability. SSTR-targeted PET provides superior molecular characterization, enhancing diagnostic accuracy, treatment precision, and surveillance beyond conventional imaging. The theranostic platform enables both precise visualization and targeted radionuclide therapy. Prospective multicenter trials with standardized protocols are essential to establish evidence-based clinical guidelines.

FGFR1 overexpression is strongly correlated with tumorigenesis, malignant progression, and poor clinical outcomes of nonsmall cell lung cancer (NSCLC). The development of PET radiotracers specifically targeting FGFR1 holds significant clinical value for guiding FGFR1-targeted therapy, evaluating treatment efficacy, and monitoring drug resistance. In this study, we used computational simulation approaches to develop linear peptide RY9 along with cyclic peptides cRY9 and cRY9M, derived from FGF2, a particular ligand of FGFR1, and designed FGFR1-targeting radiotracers [68Ga]Ga-NOTA-RY9, [68Ga]Ga-NOTA-cRY9 and [68Ga]Ga-NOTA-cRY9M for detecting the FGFR1 expression. In comparison to [68Ga]Ga-NOTA-RY9 and [68Ga]Ga-NOTA-cRY9, [68Ga]Ga-NOTA-cRY9M demonstrated superior FGFR1-binding affinity, enhanced in vivo stability, and a significantly improved tumor-to-background ratio (TBR). Notably, PET imaging revealed that [68Ga]Ga-NOTA-cRY9M exhibited significant and specific tumor uptake in FGFR1-positive NSCLC cell-derived xenograft (CDX) models and patient-derived xenograft (PDX) models. These results demonstrate that the cyclic peptide-based radiotracer [68Ga]Ga-NOTA-cRY9M serves as a potential diagnostic agent for FGFR1-expressing tumors.

Psychiatric and neurological disorders severely compromised patients' quality of life. Despite their urgent needs, the development of diagnostics and therapeutics based on the biological basis has made only little progress. This is due to limited evidence on the biological basis of these disorders in humans. Synapses are fundamental structural units of neurotransmission, and neuropsychiatric disorders are considered as 'synapse diseases'. Thus, a translational approach based on synaptic physiology is important to understand these disorders. Excitatory glutamatergic synapses play principal roles in neuronal functions. Glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental molecule of glutamatergic neurotransmission and therefore is considered to be a promising translational target. Here we review the limitations of current diagnostics and therapeutics of psychiatric disorders and claim the essential need for the promotion of translational medicine based on the synaptic physiology of AMPAR. Further, we introduce our recent translational challenge to tackle these diseases by targeting AMPARs.

Cyclin-dependent kinases 4 and 6 (CDK4/6) are essential drivers of cell cycle progression and have been validated as important therapeutic targets in oncology. In this study, we report the design, synthesis, and preclinical validation of a series of novel radiotracers ([68Ga]Ga-PY01-[68Ga]Ga-PY08) based on the pharmacophore of CDK4/6 inhibitor ribociclib. Flexible linkers and functionalized amino acids were incorporated to optimize pharmacokinetic and targeting properties. Among eight radiotracers, [68Ga]Ga-PY03 showed superior pharmacological and pharmacokinetic properties, including high stability, strong CDK4/6 binding affinity and low nonspecific uptake. Micro-PET/CT imaging demonstrated its capability to detect CDK4/6-overexpressed tumors and dynamically monitor CDK4/6 expression post-therapeutic. Importantly, [68Ga]Ga-PY03 also enabled quantitative assessment of CDK4/6 target occupancy, providing a potential tool for therapy response evaluation. In summary, these findings demonstrate the potential of [68Ga]Ga-PY03 as a PET radiotracer to monitor the CDK4/6 expression in tumors.

PET imaging of synaptic vesicle glycoprotein 2A (SV2A) has proven to be a powerful research tool for neurologic disorders. Dynamic SV2A PET scans provide data related to cerebral blood flow and SV2A density, which have been shown to be altered in neurologic disorders such as Alzheimer disease. [18F]SynVesT-2, an SV2A PET tracer, has demonstrated fast brain kinetics and high specific binding in human brains. To improve clinical feasibility, we evaluated the performance of 3 simplified reference tissue models (SRTMs) in the quantification of [18F]SynVesT-2 PET data and the minimum scan times required for reliable estimation of relative cerebral blood flow and SV2A density. Methods: Data were pooled from 14 [18F]SynVesT-2 scans acquired from 9 healthy volunteers. An SRTM, SRTM with a fitted regionally coupled k' 2 (SRTMC), and SRTM with a population-based k' 2 (SRTM2) with the centrum semiovale and cerebellum as reference regions were used to calculate nondisplaceable binding potential (BPND) and distribution volume ratio (DVR), respectively, as well as the relative tracer delivery rate (R 1). Test-retest variability (TRV), absolute TRV, and the minimum scan duration for the reliable estimation of R 1, BPND, and DVR were additionally evaluated. Results: Despite time-activity curves being well-described by all 3 models, SRTM generated unreliable BPND and DVR values in 9% and 12% of the regions of interest, respectively. SRTMC and SRTM2 resulted in BPND and DVR values consistent with those generated from the 1-tissue compartment model. On the basis of the time stability analysis, BPND and DVR estimated using SRTM2 converged after 40 min. Using SRTM2, the TRV and absolute TRV estimated from 40-min dynamic scans were -1.0 ± 11.5% and 9.9 ± 5.8% for BPND and 1.7 ± 4.0% and 3.6 ± 2.5% for DVR. Conclusion: The parameters of relative cerebral blood flow (R 1) and specific binding (BPND and DVR) can be reliably estimated from a 40-min dynamic [18F]SynVesT-2 PET scan by SRTM2, which is 30 min shorter than that required for [11C]UCB-J and [18F]SynVesT-1. The shortened scan time enables the clinical application of dynamic SV2A PET scans to maximize the physiologically relevant information attainable from a single scan.

The heterogeneous expression of tumor biomarkers limits the diagnostic performance of single-target imaging agents. Carbonic anhydrase IX (CAIX) is highly expressed in hypoxic regions of clear cell renal cell carcinoma (ccRCC) and multiple solid tumors, whereas prostate-specific membrane antigen (PSMA) is specifically upregulated in tumor-associated neovasculature. Both targets have been implicated in tumor metastasis and poor clinical outcomes. This study aimed to design and evaluate a novel bispecific PET tracer, [68Ga]Ga-PCA, targeting both CAIX and PSMA, with the goal of achieving improved tumor-specific uptake. Subcutaneous xenograft models were established in nude mice by inoculation with OS-RC-2, PC3-PIP, and HEK-293 cells. PET/CT imaging and biodistribution studies were performed following intravenous administration of [68Ga]Ga-PCA. Target specificity was evaluated via competitive blocking assays employing excess unlabeled ligand. Immunohistochemical staining was performed to validate the expression profiles of the targets within the tumors. After being labeled with gallium-68, [68Ga]Ga-PCA showed favorable physicochemical properties, such as a high radiolabeling yield (>80%), radiochemical purity over 95%, good stability in vitro, and an albumin-binding rate of 93.44 ± 0.81%. PET/CT imaging revealed pronounced and specific tracer accumulation in both OS-RC-2 and PC3-PIP tumor models. In OS-RC-2 tumors (PSMA+/CAIX+), the SUVmax (13.10 ± 0.84) was higher than those of the single-target tracers [68Ga]Ga-DOTA-NY104 (5.31 ± 0.77) and [68Ga]Ga-PSMA (2.31 ± 0.49) at 60 min postinjection. An excess of unlabeled DOTA-NY104, a PSMA-targeted ligand, or a mix of the two ligands can block the uptake of [68Ga]Ga-PCA. These results demonstrate that the tracer can bind to both targets at once. In conclusion, [68Ga]Ga-PCA is a bispecific PET tracer that targets both hypoxic tumor cells and tumor neovasculature by binding to both CAIX and PSMA. The probe exhibited significant specificity, advantageous imaging contrast, and robust blocking validation, indicating its potential for molecular imaging of malignancies, including clear cell renal cell carcinoma (ccRCC).

CD38 is an established biomarker of multiple myeloma (MM), and peptide-based radiopharmaceuticals targeted to this receptor offer a route to molecularly specific imaging. In this work, we identified a novel CD38-targeted peptide sequence (HAPWFRGGGGS) through phage display and synthesized it using automated solid-phase peptide synthesis. The peptide was modified by introducing a PEG4 spacer and on-resin conjugation of the DIAMSAR chelator, which forms a stable complex with Copper-64 (Cu-64), yielding DIAMSAR-PEG4-HAPWFRGGGGS (Monomer_L). [64Cu]Cu-Monomer_L was radiolabeled with high molar activity (>98% yield, ∼65 MBq/nmol) but showed suboptimal serum stability (∼45% intact at 2 h). To improve in vivo stability, the l-amino acid sequence was replaced with d-amino acid (Monomer_D), resulting in >90% serum stability and enhanced binding affinity toward CD38, as demonstrated by molecular docking and cell-binding assays in CD38-expressing MOLP2 human MM cells. To further increase avidity, a dimeric analog (Dimer_D) was designed by linking two Monomer_D units via a PEG4 linker. In viable MOLP2 MM cells, tracer uptake ranked as [64Cu]Cu-Dimer_D > [64Cu]Cu-Monomer_D > [64Cu]Cu-Monomer_L, and was markedly reduced by excess unlabeled peptide, confirming CD38-specific binding. Binding specificity and functional engagement of CD38 were further supported by antibody-blocking, enzymatic activity inhibition, and cellular internalization studies. Replacement of L-with d-amino acids improved binding affinity, lowering the Kd from 1043 nM ([64Cu]Cu-Monomer_L) to ∼740 nM ([64Cu]Cu-Monomer_D). The dimerization further lowered the Kd (∼730 nM) with markedly higher Bmax (6993 fmol/mg vs 3024 fmol/mg), consistent with avidity-driven enhancement in receptor engagement. In vivo small animal dynamic PET/CT and ex vivo biodistribution were performed in disseminated and subcutaneous MOLP2-CBR-GFP MM models with naïve controls. Uptake increased with peptide valency, showing maximum femoral uptake of 1.52 ± 0.35 and 2.93 ± 0.68% ID/mL for [64Cu]Cu-Monomer_D and [64Cu]Cu-Dimer_D, respectively, whereas naïve mice exhibited <1% ID/mL over 0-2 h post injection (3-4 MBq; 45-50 pmol). In the subcutaneous model, [64Cu]Cu-Dimer_D enabled clear tumor visualization at 2 h post injection with 4.66 ± 0.20% ID/mL uptake and a T/M ratio of 10.6 ± 3.1. Ex vivo tissue biodistribution confirmed higher femoral uptake (2.26 ± 0.42% ID/g) and femur-to-muscle ratio (18.17 ± 3.26). Autoradiography of excised tissues corroborated tracer localization to tumor-rich regions. Overall, [64Cu]Cu-Dimer_D demonstrates high stability, avidity, and translational promise as a CD38-targeted PET tracer for MM.

Alzheimer disease (AD) is the most common cause of dementia and one of the leading causes of death in adults age 65 y or older in the United States. AD presents with symptoms of cognitive impairment that worsen with disease progression, ultimately affecting an individual's functional abilities, independence, and overall health. Historically, treatment has relied on the mitigation of the adverse effects of the disease; however, the recent development of antiamyloid monoclonal antibodies allows for the targeting of pathologic factors that drive the progression of disease. Nuclear medicine has established itself as a useful tool in the evaluation of AD through the use of PET tracers, which target pathologic biomarkers such as amyloid-β and tau proteins, as well as metabolic processes reflective of neurodegenerative damage. Amyloid-β PET imaging and quantification have recently gained interest for their ability to more effectively diagnose AD and identify patients eligible for treatment with new antiamyloid therapies.

In-house production of FDG is increasingly necessary to ensure a stable supply of PET tracers. However, the establishment of new production facilities is often accompanied by unforeseen technical challenges. Transforming such challenges into educational experiences may play an important role in developing skilled radiology technologists. In-house FDG production training that incorporates real-world troubleshooting cases fosters skilled and confident technologists. This study aimed to evaluate the effectiveness of an educational approach that integrates real-world troubleshooting experiences encountered during the establishment of an FDG production system into training for radiology technologists. Methods: At our newly launched theranostics center, 4 radiology technologists were trained to perform FDG synthesis using a cyclotron and an automated synthesis module. Challenges encountered in the early phase (e.g., cassette-loading errors, errors in gas supply operation, mistakes in handling reagents) were systematically documented. These cases were incorporated into training manuals, simulation sessions, and on-site drills. Educational outcomes were evaluated qualitatively through feedback, competency assessments, and operational stability. Radiation exposure was monitored as a supplemental safety measure. Results: The documentation and sharing of early-stage troubleshooting cases facilitated the development of practical manuals and scenario-based simulations for FDG production. Radiology technologists demonstrated improved confidence and decision-making in handling synthesis tasks. The FDG production process achieved stable operation within several months. Occupational doses for technologists remained well below regulatory limits, supporting the safety of the training approach. Conclusion: Educational use of early troubleshooting experiences effectively enhanced radiology technologists' competencies in FDG production. This strategy provides a sustainable model for workforce development in nuclear medicine facilities worldwide.

Gamma-aminobutyric acid type A (GABA-A) receptors are the principal inhibitory neurotransmitter receptors in the central nervous system (CNS), but their functions in the peripheral nervous system (PNS) and organs such as the heart remain poorly understood. These receptors comprise various subtypes based on subunit composition with differential brain and heart expression linked to distinct pathologies. Current positron emission tomography (PET) imaging protocols use radioligands lacking subtype specificity. To address this, we developed a PET tracer targeting the α1 subunit. The α1-specific single-chain variable fragment (scFv) 1F4 was engineered from the variable domains of monoclonal antibody (mAb) 1F4. It was efficiently 18F-labeled under mild conditions via biorthogonal inverse electron demand Diels-Alder (iEDDA) ligation. PET biodistribution in mice showed favorable pharmacokinetics for [18F]F-Tz-TCO-scFv 1F4 with specific α1 subunit binding in the brain, heart, and lungs. This tracer promises to evaluate GABA-A α1 distribution and expression in peripheral organs, particularly the heart.