Carbon-11 Labeled Sarcosine: Mechanism of Action and Initial Performance in Prostate Cancer

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

? DESCRIPTION (provided by applicant): The performance of current prostate cancer (PCa) imaging is unsatisfactory. Clinicians need a diagnostic imaging approach that reveals primary PCa location, its clinical significance and predicts its malignant potential. Furthermore, the detection of recurrent disease is often difficult after definitive treatment, hampering effective local salvage treatments. Also given new systemic treatment option in metastatic PCa, the selection of treatment options and monitoring of treatment success early (via imaging) may benefit patients and reduce costs by avoiding ineffective systemic treatments. Using metabolomic profiling, tissue levels of sarcosine have been identified to be elevated in primary PCa with further increase during PCa progression. Our preclinical data show that micro-PET with 11C- sarcosine outperforms 11C-choline in prostate cancer tumor models. Based on these encouraging data, we hypothesize that PET imaging with 11C-sarcosine is able to identify primary and metastatic PCa for staging and response evaluation in humans. The study goals are to conduct a pilot trial using 11C- sarcosine as PET tracer for PCa and to evaluate the uptake mechanisms and metabolic pathways of 11C-sarcosine in human PCa tissue. Objectives: (1) Development of 11C-sarcosine as PET tracer for human use, (2) conduction of a pilot study with 11C-sarcosine in human prostate cancer subjects to collect preliminary efficacy and to assess feasibility, (3) measurement of the human radiation dosimetry of 11C-sarcosine, and (4) assessment of sarcosine uptake regulation in human prostate cancer tissue samples. Study design: The current 11C-sarcosine production will be modified according to GMP standards (aim 1). To assess aim 2, human prostate cancer subjects will undergo PET/CT imaging with 11C-sarcosine and 11C-choline to directly compare biodistribution and tumor uptake. The study will include PCa subjects undergoing prostatectomy (group A) and recurrent and/or metastatic disease (group B). The human radiation dosimetry of 11C-sarcosine is determined in normal volunteers (aim 3). For aim 4, tumor tissue samples will undergo standard pathology and target metabolite analysis based on liquid-and-gas- chromatography mass spectrometry techniques to specifically assess the metabolic pathways for sarcosine in prostate cancer and to compare these with 11C-sarcosine uptake measurements. Impact: If successful, this study would lead to a novel molecular imaging strategy for PCa, differentiating PCa from normal benign tissues, and overcome current limitation in staging and monitoring prostate cancer treatments.