The Journal of Nuclear Medicine最新文献

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors and low expression of the human epidermal growth factor receptor 2 gene. Radiolabeled amino acids (AAs) have the ability to specifically target the enhanced AA transport and modified metabolic pathways present in breast cancer cells. The primary objective of this study was to compare the uptake of AA PET tracers targeting different AA transporter systems in 2 mouse models to assess their potential for imaging TNBC. Methods: The AA PET tracers (R)-3-[¹⁸F]fluoro-2-methyl-2-(N-methylamino)propanoic acid (¹⁸F-MeFAMP, system A transport), (S)-2-amino-3-[1-(2-[¹⁸F]fluoroethyl)-¹H-[1,2,3]triazol-4-yl]propanoic acid (¹⁸F-AFETP, cationic and neutral transport), and ¹⁸F-fluciclovine (system ASC transport) were compared with ¹⁸F-FDG in primary tumor orthotopic syngeneic (4T1, n = 10) and patient-derived xenograft (BCM3936, n = 8) models of TNBC. SUV, tumor-to-brain ratios, and tumor-to-muscle ratios were quantified. Quantitative analysis of AA transporter immunohistochemistry was conducted and compared with the imaging results. Results: AA PET tracers demonstrated uptake levels in primary TNBC tumors comparable to those with ¹⁸F-FDG, with varying uptake across tracers. All AA tracers demonstrated higher tumor–to–normal tissue ratios than did ¹⁸F-FDG across multiple organs. The highest tumor-to-brain ratios were observed for ¹⁸F-MeFAMP (4T1 model) and ¹⁸F-AFETP (PDX BCM3936 model). ¹⁸F-MeFAMP showed the highest tumor-to-muscle ratios in both models, followed by ¹⁸F-AFETP and ¹⁸F-fluciclovine. Tumor-to-bone and tumor-to-liver ratios consistently favored AA tracers, with ¹⁸F-AFETP demonstrating superior tumor-to-liver contrast because of low hepatic uptake. ¹⁸F-MeFAMP, ¹⁸F-AFETP, and ¹⁸F-fluciclovine showed positive but complex correlations between SUV and corresponding AA transporters in immunohistochemical analysis. Conclusion: The AA PET tracers evaluated in this study demonstrated promising imaging properties in TNBC models compared with ¹⁸F-FDG, with higher tumor-to-brain ratios and tumor-to-muscle ratios observed across both models. Although these findings highlight the potential of AA tracers for imaging primary tumors and metastases, they also support the continued investigation of AA PET tracers as complementary tools to ¹⁸F-FDG to characterize TNBC biology as well as other aggressive cancers.

High expression of fibroblast activation protein (FAP) has been associated with inferior survival in several tumor entities. Novel ⁶⁸Ga-radiolabeled FAP inhibitors (⁶⁸Ga-FAPIs) allow noninvasive measurement of FAP, which enables the development of prognostic imaging parameters from ⁶⁸Ga-FAPI PET/CT. In this study, we compared the prognostic value of ⁶⁸Ga-FAPI-46 with ¹⁸F-FDG PET in a cohort of patients with malignant pleural mesothelioma from the FAPI PET observational trial (NCT04571086). Methods: Between May 2020 and January 2024, 49 patients with suspected or proven malignant mesothelioma were recruited, 39 of whom were eligible for data analysis. All patients underwent ⁶⁸Ga-FAPI-46 and ¹⁸F-FDG PET/CT less than 4 wk apart. Tumor burden was measured semiautomatically, and SUV_max, SUV_mean, and volumetric parameters (metabolic tumor volume [MTV], total lesion glycolysis/total lesion fibroblast activation, and total tumor SUV) were calculated. The FAP immunoreactive score (IRS) was calculated for tumor samples from a subset of patients (n = 19). Overall survival and progression-free survival were assessed per revised mRECIST (version 1.1). Survival analyses were performed with univariate and multivariate Cox regression and with Kaplan–Meier curves for clinical and imaging parameters, stratified by median. Results: Univariate analysis showed significant survival differences for all volumetric parameters for ⁶⁸Ga-FAPI-46 and ¹⁸F-FDG (e.g., ⁶⁸Ga-FAPI-46 MTV, 262 d vs. 737 d; P = 0.008 vs. ¹⁸F-FDG MTV, 336 d vs. 760 d; P = 0.012). Multivariate analysis revealed that MTV was an independent prognostic marker for ⁶⁸Ga-FAPI-46 (hazard ratio, 4.44; 95% CI, 1.20–16.43; P = 0.025) and ¹⁸F-FDG (hazard ratio, 7.01; 95% CI, 1.29–38.2; P = 0.024). Kaplan–Meier analysis of the FAP IRS found that a higher IRS was associated with poorer survival (438 d with an IRS of 0–3 vs. 1,076 d with an IRS of 4–12; P = 0.04), but no significant difference was observed in univariate and multivariate analyses. Conclusion: In this modest exploratory cohort of patients with malignant pleural mesothelioma, MTV determined by ⁶⁸Ga-FAPI-46 and ¹⁸F-FDG PET/CT had similar prognostic value, and high MTV was an independent risk factor. ⁶⁸Ga-FAPI-46 not only complements a diagnostic work-up but also provides prognostic value and could offer alternative theranostic strategies for these patients.

Neuroimaging markers predicting response to regorafenib in patients with glioma relapse remain scarce; we evaluated whether early changes in amino acid PET and MRI are associated with overall survival (OS). Methods: Twenty adult patients with central nervous system World Health Organization grade 3 or 4 gliomas at relapse (glioblastoma, 85%) were treated according to the REGOMA trial. Amino acid PET using the tracer O-(2-[¹⁸F]fluoroethyl)-l-tyrosine (¹⁸F-FET) and MRI were performed at baseline and after 2 cycles. From these imaging data, tumor-to-brain ratios (TBR), metabolic tumor volumes, the dynamic parameters (time to peak and slope), and apparent diffusion coefficients were obtained. Parameter thresholds to predict an OS of 6 mo or longer as a surrogate for response were defined using receiver operating characteristic curve analyses. In addition, Response Assessment in Neuro-Oncology criteria for MRI and PET were used to evaluate response. The association of imaging parameters with OS was evaluated using univariate and multivariate survival estimates. Results: Patients received a median of 3 regorafenib cycles (range, 2–16 cycles). The median follow-up was 10.3 mo (range, 3.2–27.6 mo). A decline in mean TBR values by 10% or greater was significantly associated with longer OS (10.4 vs. 5.3 mo; P = 0.027). Other ¹⁸F-FET PET parameters, Response Assessment in Neuro-Oncology criteria for MRI and PET, and apparent diffusion coefficient values were not associated with OS (P > 0.05). At follow-up, a mean TBR of 2.0 or less was associated with longer OS (10.6 vs. 4.5 mo; P = 0.009). Multivariate survival analyses revealed that changes in mean TBR values were independently associated with longer OS (P = 0.006; hazard ratio, 0.200), and a lower mean TBR at follow-up was strongly prognostic (P < 0.001; hazard ratio, 0.030). Conclusion: ¹⁸F-FET PET parameters are clinically valuable for identifying responders to regorafenib early after treatment initiation.

Radiopharmaceutical therapy (RPT) combined with external beam radiotherapy (EBRT) is emerging as a powerful approach in prostate cancer treatment. Historically rooted in early ⁸⁹Sr trials, this combination leverages EBRT’s precise targeting of visible tumors and RPT’s ability to address microscopic or systemic disease. Clinical and preclinical evidence shows enhanced tumor control, improved pain relief, and improved quality of life with manageable toxicity. Advanced imaging—particularly prostate-specific membrane antigen (PSMA) PET—plays a pivotal role in precise disease mapping, patient selection, and therapeutic planning. PSMA-targeted RPT, including ¹⁷⁷Lu-PSMA, expands the arsenal by delivering systemic radiation to PSMA-expressing cancer cells, with demonstrated overall survival benefits so far primarily in metastatic castration-resistant prostate cancer after androgen receptor pathway inhibitors and taxane therapies. Although practical challenges such as access, regulation, and dosimetry remain, ongoing trials are exploring concurrent and sequential strategies, including α-emitter radioligands, aiming to improve survival. As evidence accumulates and logistical barriers are addressed, combined RPT and EBRT is poised to become a standard, personalized treatment paradigm in prostate cancer care.