An in vivo imaging approach for simultaneously assessing tumor response and cytotoxicity-induced tissue response in chemotherapy.

Abstract

In chemotherapeutic treatments, while cancer cells are the primary target, cytotoxic side effects are an important consideration. In the current study, we applied an in vivo imaging tool for characterizing chemotherapeutic response in a preclinical setting. The study focused on simultaneously examining the tumor and tissue response as a result of treatment with bortezomib, a mainstay proteasome inhibitor for treating multiple myeloma, in a preclinical model. OPM-2 tumor-bearing SCID-beige mice were designated as control or treated with bortezomib (1 mg/kg, i.v., every 4 days) (n = 8 per group). ^99mTc-duramycin SPECT/CT whole-body scans were acquired 2 days before treatment as baseline and at days 1, 3 and 5 after treatment. Radioactivity uptake in tissues and organs was determined and quantitatively compared between control and bortezomib-treated group at each of the time points. Based on the imaging data, separate groups of tumor-bearing mice (n = 3 each) were included as control and bortezomib treated and the tissues were collected on day 5 for histopathology. In vivo imaging data identified significantly elevated ^99mTc-duramycin uptake in the tumor, particularly in tumoral periphery. This was accompanied with signal changes in multiple organs and tissues including the adipose tissue, major bones, abdominal regions, spleen and testes. The imaging findings were consistent with known cytotoxic side effects of bortezomib and were supported by histopathology. The outcome of the study demonstrated potential utilities of the technology by enabling timely determination of the efficacy of anticancer treatments and the effect on collateral tissues as a result of systemic cytotoxic treatment.