Akintayo, Akinyemi A.

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, [68Ga]Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of [68Ga]Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: [68Ga]Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those, 2/17 had NePC. A semiquantitative analysis with standardized uptake values (SUV) (e.g., SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. [68Ga]Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastatic lesion with identifiable [68Ga]Ga-DOTATATE uptake. Marked [68Ga]Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. Three patients had mild [68Ga]Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after [68Ga]Ga-DOTATATE imaging. Conclusions: [68Ga]Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with [68Ga]Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.

Abstract Background The ability to accurately monitor response to treatment in patients with metastatic castration resistant prostate cancer (mCRPC) on chemotherapy has been a challenge. Conventional methods of therapy response assessment have limitations and molecular imaging has been explored as an important alternative. We set out t o determine if anti-1-amino-3-anti-1-amino-3-[18F]-fluorocyclobutane-1-carboxylic acid ([18F]fluciclovine) positron emission tomography/computed tomography (PET/CT) changes reflect response to docetaxel chemotherapy in mCRPC. Results Seven patients with mCRPC were enrolled. Each patient was scheduled to have [18F]fluciclovine PET/CT at baseline, and after 1 and 6 cycles of chemotherapy. Uptake parameters were recorded in the prostate/bed and up to 10 metastatic lesions. Decrease in uptake of ≥30% was considered response (R); appearance of new lesions or >30% increase in uptake was progressive disease (PD); and change of < 30% uptake was stable disease (SD). Prostate specific antigen (PSA) was obtained at baseline and before each cycle. Bone scintigraphy and CT were acquired at baseline and after the 6th cycle. Assessment of response was based on Prostate Cancer Clinical Trial Working Group 3 recommendations. Correlation between [18F]fluciclovine uptake and time to PSA progression was also determined. All patients completed the 1 st and 2 nd [18F]fluciclovine PET/CT, while 4/7 patients completed all 3 scans. PET response correlated with PSA response in 3/7 (42.9%) patients and 3/4 (75%) patients after 1 and 6 cycles of docetaxel, respectively. Bone scan and CT correlated with PSA response in 1/4 (25%) patients. Mean SUVmax and SUVmean were significantly higher in patients with progressive disease versus non-progressive disease after 6 cycles of docetaxel (p<0.05), but not at baseline or after 1 cycle of docetaxel. There was non-significant correlation of changes in [18F]fluciclovine uptake with changes in PSA after 1 and 6 cycles of docetaxel. There was no significant correlation between PET parameters and time to PSA progression. Conclusion [18F]fluciclovine PET/CT has better correlation than CT or bone scan with PSA response for patients with mCRPC treated with docetaxel. [18F]fluciclovine PET/CT did not predict time to PSA progression. Larger studies exploring the utility of [18F]fluciclovine PET for response assessment are recommended.