Diagnostic detection of systemic prostate cancer in a mouse metastatic model: Evaluation using Micro-SPECT, Micro-CT, and Micro-MRI

Abstract

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Objectives: Systemic metastasis is a common phenomenon in advanced prostate cancer with the majority of tumor burden within bone at the time of death. Models of systemic metastasis for therapy research continue to be challenged by identification of total tumor burden to evaluate therapeutic benefit. Herein, we evaluated an ¹¹¹In radiolabeled bombesin receptor (BB2r) antagonist, ¹¹¹In-DOTA-8AOC-[(D)Phe⁶]BBN(7-13)NHEt, to determine its utility in lesion localization as compared to Micro-CT and Micro-MRI.

Methods: Male SCID mice were inoculated by intracardiac injection with 1x10⁶ androgen independent prostate cancer cells (PC-3). Whole body Micro-CT and Micro-MRI images were obtained on weeks 3-5 post inoculation with ¹¹¹In-BB2r antagonist SPECT imaging conducted on week 5.

Results: Metastatic lesions were found in the skull, mandible, bilateral scapulas, bilateral humerus, bilateral adrenal glands, lumbar vertebra, pubis, bilateral ilium, femurs and tibias as identified by Micro-CT and Micro-MRI. Micro-SPECT utilizing the ¹¹¹In-BB2r antagonist identified 60% (15/25) of lesions as compared to Micro-MRI and Micro-CT which identified 76% (19/25) and 88% (22/25) respectively.

Conclusions: ¹¹¹In-DOTA-8AOC-[(D)Phe⁶]BBN(7-13)NHEt SPECT imaging demonstrates the capability of this agent to target the majority of metastatic prostate cancer lesions identified in a systemic xenograft model. Prostate metastases not identified could be the result of lack of BB2r receptor expression, poor vascular drug delivery to metastatic sites, or volumetric spatial resolution limitation of Micro-SPECT due to sub-millimeter tumor volumes.

Research Support: NIH Training Grant T32-RR07004 and the U.S. Department of Veterans Affairs