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Simple Summary: Prostate cancer is the most prevalent cancer among men. Patients diagnosed with metastatic, castration-resistant prostate cancer (mCRPC) face a highly aggressive disease and reduced overall survival. For these patients, [177Lu]Lu-PSMA-617 has shown promising results. However, this therapy may not benefit patients with low or heterogeneous PSMA expression. The gastrin-releasing peptide receptor (GRPr) is highly expressed in prostate cancer and other cancer cells, and [177Lu]Lu-labeled GRPr-ligands have demonstrated good tumor uptake and retention, with minimal uptake in healthy tissues. However, the level of GRPr expression in advanced mCRPC patients remains elusive. In this study, we compared [68Ga]Ga-RM2 with [68Ga]Ga-PSMA-11 in a Latin American mCRPC cohort to evaluate the clinical utility of [68Ga]Ga-RM2 in this group of patients. Although GRPr is overexpressed in the early stages of prostate cancer, our results indicate that in more advanced stages, such as mCRPC, the expression is lower than PSMA. Background: The gastrin-releasing peptide receptor (GRPr) is highly overexpressed in several solid tumors, including treatment-naïve and recurrent prostate cancer. [68Ga]Ga-RM2 is a well-established radiotracer for PET imaging of GRPr, and [177Lu]Lu-RM2 has been proposed as a therapeutic alternative for patients with heterogeneous and/or low expression of PSMA. In this study, we aimed to evaluate the expression of GRPr and PSMA in a group of patients diagnosed with castration-resistant prostate cancer (mCRPC) by means of PET imaging. Methods: Seventeen mCRPC patients referred for radio-ligand therapy (RLT) were enrolled and underwent [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 PET/CT imaging, 8.8 ± 8.6 days apart, to compare the biodistribution of each tracer. Uptake in healthy organs and tumor lesions was assessed by SUV values, and tumor-to-background ratios were analyzed. Results: [68Ga]Ga-PSMA-11 showed significantly higher uptake in tumor lesions in bone, lymph nodes, prostate, and soft tissues and detected 23% more lesions compared to [68Ga]Ga-RM2. In 4/17 patients (23.5%), the biodistribution of both tracers was comparable. Conclusions: Our results show that in our cohort of mCRPC patients, PSMA expression was higher compared to GRPr. Nevertheless, RLT with [177Lu]Lu-RM2 may be an alternative treatment option for selected patients or patients in earlier disease stages, such as biochemical recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present work we investigated the clinical utility of Al[18F]F-NOTA-Octreotide (Al[18F]F-OC) in comparison to [68Ga]Ga-DOTA-TATE in patients diagnosed with neuroendocrine tumours. Our aim was to verify the recently published, promising results for Al[18F]F-NOTA-Octreotide in the Latin-American population. Al[18F]F-NOTA-Octreotide provided excellent image quality, detected NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE. PET imaging of neuroendocrine tumours (NET) is well established for staging and therapy follow-up. The short half-life, increasing costs, and regulatory issues significantly limit the availability of approved imaging agents, such as [68Ga]Ga-DOTA-TATE. Al[18F]F-NOTA-Octreotide provides a similar biodistribution and tumour uptake, can be produced on a large scale and may improve access to precision imaging. Here we prospectively compared the clinical utility of [68Ga]Ga-DOTA-TATE and Al[18F]F-NOTA-Octreotide in the Latin-American population. Our results showed that in patients with stage IV NETs [68Ga]Ga-DOTA-TATE presents higher physiological uptake than Al[18F]F-NOTA-Octreotide in the liver, hypophysis, salivary glands, adrenal glands (all p < 0.001), pancreatic uncinated process, kidneys, and small intestine (all p < 0.05). Nevertheless, despite the lower background uptake of Al[18F]F-NOTA-Octreotide, comparative analysis of tumour-to-liver (TLR) and tumour-to-spleen (TSR) showed no statistically significant difference for lesions in the liver, bone, lymph nodes, and other tissues. Only three discordant lesions in highly-metastases livers were detected by [68Ga]Ga-DOTA-TATE but not by Al[18F]F-NOTA-Octreotide and only one discordant lesion was detected by Al[18F]F-NOTA-Octreotide but not by [68Ga]Ga-DOTA-TATE. Non-inferiority analysis showed that Al[18F]F-NOTA-Octreotide is comparable to [68Ga]Ga-DOTA-TATE. Hence, our results demonstrate that Al[18F]F-NOTA-Octreotide provided excellent image quality, visualized NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE. [ABSTRACT FROM AUTHOR]