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

Abstract

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.

Advances in 177Lu-PSMA and 225Ac-PSMA Radionuclide Therapy for Metastatic Castration-Resistant Prostate Cancer

“…On the side note, it is important to mention that some patients, who were treated with either 177 Lu-PSMA or 225 Ac-PSMA or tandem therapy, do not show any treatment response at all due to tumors without PSMA expression or due to neuroendocrine differentiation. Neuroendocrine differentiation in PCa is mostly therapy-induced (17–30%); however, in some cases it develops de novo (0.5–2%) [ 58 ].…”

18F‐FDG PET/CT imaging in neuroendocrine prostate cancer: Relation to histopathology and prognosis

“…Spratt et al reported that 18 F‐FDG PET/CT had a high sensitivity in detecting distant metastases in a 23 NEPC patients cohort 12 . And a diagnostic study showed 18 F‐FDG was the optimum radiotracers for detecting NEPC lesions 23 . In comparison, our study provided the definitive pathological diagnosis and classification of NEPC.…”

“…12 And a diagnostic study showed 18 F-FDG was the optimum radiotracers for detecting NEPC lesions. 23 In comparison, our study provided the definitive pathological diagnosis and classification of NEPC. Of note, the correlation between high 18 F-FDG uptake and SCNC suggested the potential opportunities for 18 F-FDG PET/CT to assist in diagnosing histopathological subtypes.…”

PET radiotracers for whole-body in-vivo molecular imaging of prostatic neuroendocrine malignancies: A case series and review of literature

“…Several reports support the possible high [ 18 F]FDG-avidity in cases of tiNED, particularly in soft tissue tumor lesions [39][40][41][42][43]. In a study that included 23 CRPC patients with "clinical NED" (elevated blood levels of chromogranin A), 22% of 510 bone metastases and 95% of 82 soft tissue metastases were [ 18 F]FDG-avid [40].…”