Multitarget Molecular Imaging in Metastatic Castration Resistant Adenocarcinoma Prostate Cancer with Therapy Induced Neuroendocrine Differentiation

Neuroendocrine differentiation of prostate cancer (NEDPC) includes de novo presentation and secondary to epigenetic changes, referred as therapy-induced neuroendocrine prostate cancer (t-NEPC). Molecular imaging with prostate-specific membrane antigen (PSMA) and somatostatin analogues positron emission tomography (PET/CT) in NEDPC have not been validated. ¹⁸F-FDG (fluorodeoxyglucose) PET/CT has numerous limitations in prostate cancer (PCa) and the utility in NEDPC has only been reported in a few series of cases. The objective of this study is to compare the lesions detection rate of the three radiotracers in metastatic t-NEPC patients. (1) Material and Methods: Retrospective evaluation of patients with prostate adenocarcinoma treated with androgen deprivation therapy, chemotherapy, a novel androgen receptor pathway inhibitor or a combination of them and a second tumour biopsy confirming t-NEPC was made. All patients underwent ¹⁸F PSMA-1007, ¹⁸F AlF-NOTA-Octreotide, and ¹⁸F-FDG PET/CT. Evaluation of positive lesions was determined and SUVmax of each radiotracer was estimated and correlated with computer tomography (CT) findings. (2) Results: A total of eight patients were included. The mean time from diagnosis of prostate adenocarcinoma to t-NEPC was 28.2 months, with a mean serum specific prostate antigen (PSA) of 16.6 ng/dl at the time of NEPC diagnosis. All patients were treated with antiandrogen therapy and 87.5% with chemotherapy. A total of 273 lesions were identified by CT from which 182 were detected by ¹⁸F-FDG PET/CT, 174 lesions by ¹⁸F PSMA-1007, and 59 by ¹⁸F AlF-NOTA-Octreotide. An interpatient analysis of the lesions was performed and dual tracer ¹⁸F-FDG PET/CT and ¹⁸F PSMA-1007 PET/CT detected a total of 270/273 lesions (98.9%). (3) Conclusions: NEDPC patients demonstrated wide inter and intrapatient molecular imaging heterogeneity within the three radiotracers. ¹⁸F-FDG detected most lesions in t-NEPC among all radiotracers, especially in visceral sites; ¹⁸F PSMA-1007 detected more bone lesions. ¹⁸F AlF-NOTA-Octreotide showed no significant utility.