Diagnostic efficacy of [68Ga]Ga-DOTA-GPFAPI-04 in patients with solid tumors in a head-to-head comparison with [18F]F-FDG: results from a prospective clinical study.

PURPOSE: To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG. METHODS: Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant. RESULTS: Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2-3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs. CONCLUSION: Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents.

CXCR4-Targeted 68 Ga-Pentixafor PET/CT Imaging in Inflammatory Bowel Disease.

PURPOSE: To investigate the role of CXCR4-targeted 68 Ga-pentixafor PET/CT imaging in inflammatory bowel disease (IBD). METHODS: Five IBD patients and 12 control subjects performing 68 Ga-pentixafor PET/CT examinations were included. 68 Ga-pentixafor PET/CT imaging and endoscopic findings were recorded and compared. The semiquantitative parameters of 68 Ga-pentixafor uptake by the lesion segments in IBD patients and the normal intestines in the control were investigated. RESULTS: Among these 5 IBD patients, endoscopy successfully examined a total of 26 intestinal segments, with 13 segments showing endoscopic lesions. 68 Ga-pentixafor PET/CT was positive in all endoscopy-proven lesions (13/13). Additionally, 68 Ga-pentixafor PET/CT revealed the lesions in small intestines and colons that cannot be reached by endoscopy due to severe stenosis, and mesenteric lymphadenitis accompanied IBD. The SUV max of the lesion segments in IBD patients was significantly higher than that of the normal intestines in the control group (median, 3.15 [range, 1.61-6.26] vs 1.67 [1.18-2.29], P < 0.001). Moreover, the SUV max ratios of the lesion segments/liver or blood pool were higher when compared with the control (2.20 [1.13-3.26] vs 0.85 [0.54-1.20]; 1.66 [0.94-2.95] vs 0.67 [0.52-1.04]; P ≤ 0.001). CONCLUSIONS: 68 Ga-pentixafor PET/CT can be a potentially valuable tool to assess the active intestinal lesions of IBD with high sensitivity. Moreover, this noninvasive approach does not require fasting or bowel preparation, offering good tolerance and safety.

Implications of Sarcopenia and Glucometabolism Parameters of Muscle Derived From Baseline and End-of-Treatment 18F-FDG PET/CT in Diffuse Large B-Cell Lymphoma.

OBJECTIVE: We previously found that the incidence of sarcopenia increased with declining glucose metabolism of muscle in patients with treatment-naïve diffuse large B-cell lymphoma (DLBCL). This study aimed to investigate the relationship between sarcopenia and muscle glucometabolism using 18F-FDG PET/CT at baseline and end-of-treatment, analyze the changes in these parameters through treatment, and assess their prognostic values. MATERIALS AND METHODS: The records of 103 patients with DLBCL (median 54 years [range, 21-76]; male:female, 50:53) were retrospectively reviewed. Skeletal muscle area at the third lumbar vertebral (L3) level was measured, and skeletal muscle index (SMI) was calculated to determine sarcopenia, defined as SMI < 44.77 cm²/m² and < 32.50 cm²/m² for male and female, respectively. Glucometabolic parameters of the psoas major muscle, including maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), were measured at L3 as well. Their changes across treatment were also calculated as ΔSMI, ΔSUVmax, and ΔSUVmean; Δbody mass index was also calculated. Associations between SMI and the metabolic parameters were analyzed, and their associations with progression-free survival (PFS) and overall survival (OS) were identified. RESULTS: The incidence of sarcopenia was 29.1% and 36.9% before and after treatment, respectively. SMI (P = 0.004) was lower, and sarcopenia was more frequent (P = 0.011) at end-of-treatment than at baseline. The SUVmax and SUVmean of muscle were lower (P < 0.001) in sarcopenia than in non-sarcopenia at both baseline and end-of-treatment. ΔSMI was positively correlated with ΔSUVmax of muscle (P = 0.022). Multivariable Cox regression analysis showed that sarcopenia at end-of-treatment was independently negatively associated with PFS (adjusted hazard ratio [95% confidence interval], 2.469 [1.022-5.965]), while sarcopenia at baseline was independently negatively associated with OS (5.051 [1.453-17.562]). CONCLUSION: Sarcopenic patients had lower muscle glucometabolism, and the muscular and metabolic changes across treatment were positively correlated. Sarcopenia at baseline and end-of-treatment was negatively associated with the prognosis of DLBCL.

[68Ga]Ga-labeled FAPI Conjugated with Gly-Pro Sequence for PET Imaging of Malignant Tumors.

PURPOSE: To improve tumor uptake and prolong tumor retention, a novel fibroblast activation protein (FAP) ligand based on a quinoline-based FAP inhibitor (FAPI) conjugated with the Gly-Pro sequence and 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA) was radiolabeled with [68Ga]GaCl3 ([68Ga]Ga-DOTA-GPFAPI-04). Due to the tumor heterogeneity, this study aimed to further validate the preclinical value of [68Ga]Ga-DOTA-GPFAPI-04 PET imaging in tumor mice models with different FAP expression levels. METHODS: [68Ga]Ga-DOTA-GPFAPI-04 was synthesized and its partition coefficient was measured. The stability of [68Ga]Ga-DOTA-GPFAPI-04 was tested in phosphate-buffered saline (PBS, pH 7.4) and fetal bovine serum (FBS). Small animal PET and semi-quantitative studies were conducted in Panc-1 and A549 xenograft tumor mice models compared with [68Ga]Ga-DOTA-FAPI-04. Immunofluorescent and immunohistochemical staining and western blot assay were performed to confirm FAP expression in xenograft tumors. RESULTS: [68Ga]Ga-DOTA-GPFAPI-04 exhibited a radiochemical purity of > 99% and high stability in PBS and FBS. [68Ga]Ga-DOTA-GPFAPI-04 had higher hydrophilic property than [68Ga]Ga-DOTA-FAPI-04 (-4.09 ± 0.05 vs -3.45 ± 0.05). Small animal PET and semi-quantitative analysis revealed Panc-1 xenograft tumor displayed higher tumor uptake of [68Ga]Ga-DOTA-GPFAPI-04 and tumor-to-background ratios compared to A549 xenograft tumor, consistent with the results of immunofluorescence, immunohistochemistry, and western blot. Moreover, [68Ga]Ga-DOTA-GPFAPI-04 demonstrated higher tumor accumulation and longer tumor retention than [68Ga]Ga-DOTA-FAPI-04 in both Panc-1 and A549 xenograft tumors. Furthermore, the FAP-binding specificity of [68Ga]Ga-DOTA-GPFAPI-04 was confirmed in vivo by co-injection of unlabeled GPFAPI-04. CONCLUSION: [68Ga]Ga-DOTA-GPFAPI-04 showed more favorable in vivo tumor imaging and longer tumor retention compared to [68Ga]Ga-DOTA-FAPI-04, which has high potential to be a promising PET probe for detecting FAP-positive tumors.

Association of mismatch repair deficiency in endometrial cancer with 18F-FDG PET/CT and clinicopathological features and their prognostic value.

PURPOSE: Identification of the mismatch repair (MMR) deficiency in endometrial cancer (EC) may aid in the screening of patients who may benefit from immunotherapy. Our goal was to investigate the relationship between MMR status and 18F-FDG PET/CT metabolic parameters and clinicopathological features in patients with EC, as well as to explore their prognostic value. METHODS: This retrospective study included 106 EC patients who were classified as MMR deficient (dMMR) or MMR proficient (pMMR) group based on MMR protein expression status evaluated by immunohistochemistry. Clinicopathological characteristics and PET metabolic parameters were compared between the dMMR and pMMR groups, and their relationships with MMR status and prognosis were evaluated. RESULTS: Of 106 EC patients, 30 patients (28.1%) had dMMR, while 76 (71.7%) had pMMR. Compared with the pMMR group, the dMMR group showed a lower prevalence of overweight (BMI ≥ 25) (17.2% vs. 43.9%, P = 0.019) and more lymph vascular space invasion (43.3% vs. 21.1%, P = 0.029). Although no relationship between glucometabolism parameters and MMR status was observed in all enrolled patients, higher SUVmax was observed in the endometrioid type of EC with MMR deficiency (P = 0.047). Additionally, SUVmax related to MMR status was found in EC patients with advanced FIGO stage (P = 0.026) or deep myometrial invasion (P = 0.026). Multivariate Cox regression analysis revealed that lymph node metastasis was independently predictive of PFS, while advanced FIGO stage was an independent predictor of OS. No significant association between MMR status and prognosis was found in EC. CONCLUSION: Higher SUVmax was associated with MMR deficiency in EC patients with endometrioid type, advanced stage, or deep myometrial invasion, which may be useful for predicting the MMR status and thus aiding in determination of immunotherapy for patients with EC.