Evaluation of PET Imaging Performance of the TSPO Radioligand [18F]DPA-714 in Mouse and Rat Models of Cancer and Inflammation.

ABSTRACT

PURPOSE: Many radioligands have been explored for imaging the 18-kDa translocator protein (TSPO), a diagnostic and therapeutic target for inflammation and cancer. Here, we investigated the TSPO radioligand [(18)F]DPA-714 for positron emission tomography (PET) imaging of cancer and inflammation. PROCEDURES [(18)F]DPA-714 PET imaging was performed in 8 mouse and rat models of breast and brain cancer and 4 mouse and rat models of muscular and bowel inflammation. RESULTS: [(18)F]DPA-714 showed different uptake levels in healthy organs and malignant tissues of mice and rats. Although high and displaceable [(18)F]DPA-714 binding is observed ex vivo, TSPO-positive PET imaging of peripheral lesions of cancer and inflammation in mice did not show significant lesion-to-background signal ratios. Slower [(18)F]DPA-714 metabolism and muscle clearance in mice compared to rats may explain the elevated background signal in peripheral organs in this species. CONCLUSION: Although TSPO is an evolutionary conserved protein, inter- and intra-species differences call for further exploration of the pharmacological parameters of TSPO radioligands.