Evaluation of gastrin-releasing peptide receptor, prostate-specific membrane antigen, and neurotensin receptor 1 as potential biomarkers for accurate prostate cancer stratified diagnosis.

BACKGROUND: Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis. We synthesized molecular probes targeting the markers to achieve a non-invasive precise detection of PCa patients with PET/CT imaging. METHODS: In this study, the expression of GRPR, PSMA, and NTR1 was evaluated by immunohistochemistry in 34 PIN, 171 PCa, and 22 lymph node metastasis tissues of patients. The correlation between their expression and the clinicopathological parameters of PCa patients was assessed. Sixteen PCa patients with different Gleason scores (GS) underwent dual-tracer (68Ga-NOTA-RM26 and 68Ga-NOTA-PSMA617) PET/CT. RESULTS: In the PIN stage, the expression of GRPR was significantly higher than that of PSMA and NTR1 (P < 0.001), while NTR1 expression was significantly higher than PSMA and GRPR expression in primary PCa (P = 0.001). High PSMA expression in PCa patients was associated with shorter progression-free survival (P = 0.037) and overall survival (P = 0.035). PCa patients with high GS had higher tumor uptake of 68Ga-NOTA-PSMA617 than those with low GS (P = 0.001), while PCa patients with low GS had higher tumor uptake of 68Ga-NOTA-RM26 than those with high GS (P = 0.001). CONCLUSIONS: This study presents three novel biomarkers (PSMA, GRPR, and NTR1) as imaging agents for PET/CT, and may offer a promising approach for non-invasive precise detection and Gleason grade prediction of PCa patients.

Biodistribution of 18F-AlF-NOTA-octreotide in Different Organs and Characterization of Uptake in Neuroendocrine Neoplasms.

PURPOSE: The aims of this study were threefold: [1] to describe the biodistribution of 18F-AlF-NOTA-octreotide (18F-OC) in normal organs; [2] to evaluate the range of uptake of NEN and benign lesions using the maximum standardized uptake value (SUVmax); and [3] to compare the difference in 18F-OC uptake among tumors of different grades. METHODS: This study included 162 patients (67 females and 95 males) who received 18F-OC positron emission tomography (PET)/computed tomography (CT), 128 of whom were diagnosed with neuroendocrine neoplasms (NENs). The SUVmax and SUVmean of 18F-OC were measured in 21 normal anatomical structures. We compared the differences among G1, G2, and G3 NENs, as well as between NENs and benign lesions. RESULTS: High physiological uptake of 18F-OC (SUVmax > 6.77) was detected in the spleen, adrenal gland, renal parenchyma, pituitary gland, and liver. Moderate uptake (SUVmax 3.00-6.77) was found in the uncinate process of the pancreas (PU), prostate, thyroid, and uterus. Mild uptake (SUVmax 1.34-3.00) was observed in the small intestine, pancreas (pancreas uptake except for the head of the pancreas), gallbladder, and transverse colon. The SUVmax of NENs was higher than that of benign lesions, including fractures, inflamed tissue, reactive hyperplasia, and degenerative disease. However, overlap was noted between the two groups. The SUVmax of 18F-OC uptake by tumors was significantly correlated with tumor grade in primary lesions and those of the lymph node, bone, and other sites (all P < 0.01). CONCLUSIONS: The results obtained from the majority of the samples in this study show the biodistribution of 18F-OC in normal organs and have significance as a reference. Although some benign lesions show variable uptake, the uptake by these lesions is still different from that of NENs. NENs of different grades have differences in 18F-OC uptake levels.

Evaluation of 18F-AlF-NOTA-octreotide for imaging neuroendocrine neoplasms: comparison with 68Ga-DOTATATE PET/CT.

OBJECTIVE: To evaluate the diagnostic efficacy of 18F-AlF-NOTA-octreotide (18F-OC) PET/CT compared with that of 68Ga-DOTATATE PET/CT. MATERIALS AND METHODS: Twenty patients (mean age: 52.65 years, range: 24-70 years) with biopsy-proven neuroendocrine neoplasms (NENs) were enrolled in this prospective study. We compared the biodistribution profiles in normal organs based on the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean), and uptake in NEN lesions by measuring the SUVmax on 18F-OC and 68Ga-DOTATATE PET/CT images. The tumor-to-liver ratio (TLR) and tumor-to-spleen ratio were calculated by dividing the SUVmax of different tumor lesions by the SUVmean of the liver and spleen, respectively. The Wilcoxon signed-rank test was used to compare nonparametric data. Data were expressed as the median (interquartile range). RESULTS: In most organs, there were no significant differences in the biodistribution of 68Ga-DOTATATE and 18F-OC. 18F-OC had significantly lower uptake in the salivary glands and liver than 68Ga-DOTATATE. 18F-OC detected more lesions than 68Ga-DOTATATE. The uptake of 18F-OC in the tumors was higher in most patients, but the difference was not statistically significant relative to that of 68Ga-DOTATATE. However, the TLRs of 18F-OC were higher in most patients, including for lesions in the liver (p = 0.02) and lymph nodes (p = 0.02). CONCLUSION: Relative to 68Ga-DOTATATE, 18F-OC possesses favorable characteristics with similar image quality and satisfactory NEN lesion detection rates, especially in the liver due to its low background uptake. 18F-OC therefore offers a promising clinical alternative for 68Ga-DOTATATE.

Utility of 18F-AlF-NOTA-Octreotide PET/CT in the Localization of Tumor-Induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a paraneoplastic disorder, usually caused by benign mesenchymal tumors that produce high levels of fibroblast growth factor 23. The only curative therapy is resection of the causative tumors. OBJECTIVE: This research was conducted to evaluate the efficacy of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT) in detecting TIO and its impact on patient management. METHODS: Retrospective analysis was conducted of 17 patients with hypophosphatemic osteomalacia suspected to be TIO. A  18F-OC PET/CT study was performed in all 17 patients to localize the tumor and 68Ga-DOTATATE PET/CT was performed in 4 out of 17 patients; both studies were performed within 1 week of each other. Both studies were interpreted blindly without the knowledge of other imaging findings. The image findings were compared with the results of histopathological examinations and clinical follow-ups. RESULTS: The 18F-OC PET/CT scans were positive in 14 patients. Furthermore, 4 of 14 patients were scanned with both 18F-OC and 68Ga-DOTATATE PET/CT. Both studies were able to localize the tumor in all 4 patients. In total, 14 patients had surgery to remove the lesions. Postsurgical pathological examination confirmed causative tumors in these patients, whose symptoms diminished promptly. Serum phosphate levels normalized, confirming the diagnosis of TIO. 18F-OC PET/CT sensitivity, specificity, and accuracy were 87.5%, 100%, and 88.2% respectively. 18F-OC PET/CT findings affected patient management in 88.2% of cases. CONCLUSION: 18F-OC PET/CT scan is useful in the detection of tumors causing TIO. Further studies with larger patient populations are needed to validate the result.

Clinical Application of 18F-AlF-NOTA-Octreotide PET/CT in Combination With 18F-FDG PET/CT for Imaging Neuroendocrine Neoplasms.

OBJECTIVES: The study is to evaluate biodistribution, dosimetry, safety, and clinical usefulness of F-AlF-NOTA-octreotide (F-OC) PET/CT in combination with F-FDG PET/CT for detection of neuroendocrine neoplasms (NENs). METHODS: The biodistribution, dosimetry, and safety of F-OC were evaluated in 3 healthy volunteers. Twenty-two NEN patients underwent PET/CT at 60 minutes after intravenous injection of 3.7 to 4.44 MBq (0.1-0.12 mCi) per kilogram of body weight of F-OC. This was followed by F-FDG PET/CT within a 2-week period. RESULTS: F-OC was well tolerated by all healthy volunteers and NEN patients. The calculated effective dose of F-OC was 0.023 ± 0.002 mSv/MBq. In NEN patients, we observed prominent F-OC tumor uptake and high tumor-to-background ratios. Tumor uptake of F-OC was greater than that of F-FDG, and this was particularly evident in G2 NENs (median SUVmax, 45.6 vs 4.3; P < 0.015). Tumor uptake of F-OC or F-FDG was significantly correlated with tumor differentiation (P < 0.05). Dual tracer PET/CT detected more lesions and also yielded information on the biological status of tumors. CONCLUSIONS: The tracer F-OC exhibited favorable safety and dosimetry profiles. F-OC provided superior imaging of well-differentiated NENs and significantly higher tumor-to-background ratio compared with F-FDG. Combining F-FDG with F-OC PET/CT has the potential to improve NEN staging and management of patient treatment.