EJNMMI Research最新文献

Background: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a rare autosomal dominant disorder caused by CDC73 gene mutations, predisposing individuals to primary hyperparathyroidism (pHPT), cemento-ossifying fibromas, and other neoplastic conditions. [18F]Fluorocholine PET/CT has emerged as a tool for localizing hyperfunctioning parathyroid glands in pHPT, but its application in HPT-JT syndrome remains unreported.

Case presentation: We describe the case of a 15-year-old male presenting with severe hypercalcemia, increased PTH serum levels, and a history of cemento-ossifying fibroma removal. Standard imaging, including [99mTc]Tc-MIBI scintigraphy, was inconclusive. [18F]Fluorocholine PET/CT successfully identified a hyperfunctioning parathyroid gland, identified as parathyroid atypical adenoma at subsequent histology, and a recurrent maxillary cemento-ossifying fibroma. Genetic testing confirmed a CDC73 mutation, leading to the diagnosis of HPT-JT syndrome.

Conclusions: To our knowledge, this is the first reported case utilizing [18F]Fluorocholine PET/CT for the evaluation and management of HPT-JT syndrome with active presence of a maxillary cemento-ossifying fibroma. Given its superior sensitivity compared to conventional imaging, [18F]Fluorocholine PET/CT provided critical information for surgical planning and it might be a useful diagnostic tool for long-term disease monitoring. This case highlights the potential role of [18F]Fluorocholine PET/CT in detecting both parathyroid and jaw manifestations of HPT-JT syndrome, emphasizing the need for further research into its application in hereditary endocrine disorders.

Background: Terbium-161 (Tb-161) emits internal conversion and Auger electrons, in addition to beta-minus radiation, which might be of added benefit for targeted radionuclide therapy (TRT) compared to Lutetium-177 (Lu-177). We extensively compared Lu-177 and Tb-161 for fibroblast activation protein (FAP)-targeted TRT in a preclinical setting. To study this, FAP-2286 was labeled with Lu-177 and Tb-161 and characterized in vitro on FAP-expressing cells and ex vivo using patient tumor samples. Moreover, in vivo studies (i.e. biodistribution and efficacy) were performed using a clinically representative pancreatic ductal adenocarcinoma (PDAC) mouse model. Biodistribution was performed 1, 4, 24, and 48 h post injection of 5 MBq/500 pmol [¹⁷⁷Lu]Lu-FAP-2286 or [¹⁶¹Tb]Tb-FAP-2286. Subsequently, animals were treated with 4 × 40 MBq/500 pmol [¹⁷⁷Lu]Lu-FAP-2286 or [¹⁶¹Tb]Tb-FAP-2286 and with alternating doses of 2 × 40 MBq/500 pmol of each radiopharmaceutical.

Results: No difference in [¹⁷⁷Lu]Lu-FAP-2286 and [¹⁶¹Tb]Tb-FAP-2286 uptake was observed in the cell models. In vivo studies did not show a survival benefit after 4 × 40 MBq/500 pmol [¹⁷⁷Lu]Lu-FAP-2286 or [¹⁶¹Tb]Tb-FAP-2286, while Kaplan-Meier analyses demonstrated a modest prolonged survival after tandem therapy in mice that first received [¹⁷⁷Lu]Lu-FAP-2286 followed by [¹⁶¹Tb]Tb-FAP-2286. Dosimetry calculations based on autoradiography studies on patient tumor samples showed that even with lower binding, a higher absorbed dose to the tumor can be accomplished with [¹⁶¹Tb]Tb-FAP-2286.

Conclusions: In our in vitro and in vivo studies, [¹⁷⁷Lu]Lu-FAP-2286 and [¹⁶¹Tb]Tb-FAP-2286 demonstrated similar behavior. In the applied PDAC mouse model, FAP-TRT showed limited therapeutic efficacy, most likely due to the limited radiopharmaceutical uptake observed in the tumors. This hampered determination of a potential benefit of either radioisotope for FAP-TRT. Of note, a modest response was observed in the tandem therapy group that first received [¹⁷⁷Lu]Lu-FAP-2286, followed by [¹⁶¹Tb]Tb-FAP-2286.

Background: Nectin-4 is a promising theranostic target for cancers treatment due to its high abundance/expression in different cancer entities such as bladder cancer, breast cancer, and pancreatic cancer This study evaluated the biodistribution and radiation dosimetry of [⁶⁸Ga]Ga-DOTA-Sar¹⁰-Nectin-4 ([⁶⁸Ga]Ga-FZ-NR-1), a novel Nectin-4-targeting PET tracer developed by our team, to assess its safety and support its clinical translation. Eight patients with pathologically confirmed malignancies (breast cancer, pancreatic cancer, or bladder cancer) underwent whole-body (WB) PET/CT scans at 10, 40, and 180 min after the injection of [⁶⁸Ga]Ga-FZ-NR-1. The images were reconstructed using the Ordered Subset Expectation Maximization (OSEM) algorithm with TOF and PSF technology. The brain, salivary, heart, lungs, stomach, spleen, liver, gallbladder, pancreas, kidneys, colon, and prostate in males or uterus in females as target organs were semi-automatically segmented on PET/CT images using the Hermes Internal Radiation Dosimetry (HIRD) software toolkit. Time-activity curves (TACs) were obtained for these organs based on measured activity concentrations. The time-integrated activity coefficients (TIACs) of these target organs were calculated by integrating the TACs. Organ-specific absorbed doses and the total body effective dose were estimated using IDAC-Dose 2.1 software. Meanwhile, bladder dosimetry employed a standard voiding model.

Results: [⁶⁸Ga]Ga-FZ-NR-1 was cleared rapidly, primarily via the urinary system. The highest organ absorbed doses per injected activity unit were observed in the kidneys (2.24 × 10⁻¹ mGy/MBq) and bladder wall (1.24 × 10⁻¹ mGy/MBq). Other notable organs were the salivary glands, with an absorbed dose of approximately 2.54 × 10⁻² mGy/MBq. The estimated total body effective dose per injected activity unit was approximately 2.00 × 10⁻² mSv/MBq. Preliminary clinical imaging showed high tracer uptake in breast, pancreatic, and bladder cancer lesions, highlighting its promising diagnostic potential for detecting Nectin-4-expressing tumors.

Conclusion: This human dosimetry assessment of [⁶⁸Ga]Ga-FZ-NR-1 showed a total body effective dose of approximately 2.00 × 10⁻² mSv/MBq, similar to other ⁶⁸Gallium-labeled tracers. Organ absorbed doses were well within the accepted limits, suggesting a favorable radiation risk profile for clinical application as a PET imaging agent targeting Nectin-4. Initial clinical imaging results demonstrates that [⁶⁸Ga]Ga-FZ-NR-1 provides clear visualization of both primary tumors and metastases with high Nectin-4 expression levels.