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

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Abstract

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 (SUVmax)) 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.

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Acknowledgments

We gratefully acknowledge Vahid Ravanfar for the technical assistance, Dr. Jim Slater and the Cyclotron Core Facility at UCSF for the production of 68Ga-citrate, and Drs. Randall Hawkins, Charles Ryan, John Kurhanewicz, Dan Vigneron, Sarah Nelson, and Henry VanBrocklin for the constructive comments about the manuscript. M.J.E. was supported by the National Cancer Institute (R00CA172695, R01CA176671) and a Department of Defense Idea Development Award (PC140107). M.J.E. and R.A. are Prostate Cancer Foundation Young investigators. M.J.E., R.A., and S.C.B. were supported by the UCSF Academic Senate Committee on Research. Y.S. was supported by the National Cancer Institute (R01CA154561). Research from UCSF reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health under Award Number P30CA082103.

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    Authors and Affiliations

    1. Department of Radiology and Biomedical Imaging, University of California, 185 Berry Street, Lobby 6, Suite 350, San Francisco, CA, 94107, USA

      Spencer C. Behr, Youngho Seo, Carina M. Aparici, Kenneth T. Gao, Dora H. Tao & Michael J. Evans

    2. Department of Medicine, University of California, 505 Parnassus Avenue, San Francisco, CA, 94143, USA

      Rahul Aggarwal, Emily Chang & Eric J. Small

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    1. Spencer C. Behr
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    Correspondence to Michael J. Evans.

    Ethics declarations

    The study was approved by UCSF’s Institutional Review Board (IRB).

    Conflict of Interest

    M.J.E. receives consulting fees and owns shares in ORIC Pharmaceuticals, Inc. S.C.B. receives consulting fees from GE Healthcare.

    Informed Consent

    Informed consent was obtained from all individual participants included in the study.

    Additional information

    Spencer C. Behr and Rahul Aggarwal contributed equally to this work.

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    Behr, S.C., Aggarwal, R., Seo, Y. et al. A Feasibility Study Showing [68Ga]Citrate PET Detects Prostate Cancer. Mol Imaging Biol 18, 946–951 (2016). https://doi.org/10.1007/s11307-016-0966-5

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    • DOI: https://doi.org/10.1007/s11307-016-0966-5

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