A Feasibility Study Showing [⁶⁸Ga]Citrate PET Detects Prostate Cancer

Purpose: The management of advanced or recurrent prostate cancer is limited in part by the lack of effective imaging agents. Metabolic changes in prostate cancer have previously been exploited for imaging, culminating in the recent US FDA approval of [¹¹C]choline for the detection of subclinical recurrent disease after definitive local therapy. Despite this milestone, production of [¹¹C]choline requires an on-site cyclotron, limiting the scope of medical centers at which this scan can be offered. In this pilot study, we tested whether prostate cancer could be imaged with positron emission tomography (PET) using [⁶⁸Ga]citrate, a radiotracer that targets iron metabolism but is produced without a cyclotron.

Procedures: Eight patients with castrate-resistant prostate cancer were enrolled in this single-center feasibility study. All patients had evidence of metastatic disease by standard of care imaging [X-ray computed tomography (CT), bone scan, or magnetic resonance imaging (MRI)] prior to PET with [⁶⁸Ga]citrate. Patients were intravenously injected with increasing doses of [⁶⁸Ga]citrate (136.9 to a maximum of 259 MBq). Uptake time was steadily increased from 1 h to approximately 3.5 h for the final 4 patients, and all patients were imaged with a PET/MRI. Qualitative and semi-quantitative (maximum standardized uptake value (SUV_max)) assessment of the metastatic lesions was performed and compared to the standard of care imaging.

Results: At 1- and 2-h imaging times post injection, there were no detectable lesions with [⁶⁸Ga]citrate PET. At 3- to 4-h uptake time, there were a total of 71 [⁶⁸Ga]citrate-positive lesions (67 osseous, 1 liver, and 3 lymph node). Of these, 65 lesions were visible on the standard of care imaging (CT and/or bone scan). One PET-avid osseous vertebral body metastasis was not apparent on either CT or bone scan. Twenty-five lesions were not PET-avid but seen on CT and bone scan (17 bone, 6 lymph node, 1 pleural, and 1 liver). The average of the maximum SUVs for bone or soft tissue metastases for patients treated at higher doses and uptake time was statistically higher than the corresponding parameter in normal liver, muscle, and bone. Visually obvious blood pool activity was observed even 3-4 h post injection, suggesting that further optimization of the [⁶⁸Ga]citrate imaging protocol is required to maximize signal-to-background ratios.

Conclusions: Our preliminary results support that PET with [⁶⁸Ga]citrate may be a novel tool for imaging prostate cancer. Future studies are needed to determine the optimal imaging protocol, the clinical significance of [⁶⁸Ga]citrate uptake, and its role in therapeutic decisions.