Early response assessment in renal cell carcinoma by ¹⁸F-fluorothymidine following anticancer therapy with sunitinib using xenograft model

Objectives Monitoring the early therapeutic effect of sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, in renal cell carcinoma (RCC) is important for better managing of cancer patients. This study was undertaken to determine whether ¹⁸F-Fuorothymidyne (FLT) is useful for early response assessment in RCC following sunitinib therapy using in vivo biodistribution studies of tumor-bearing mice.

Methods ACHN tumor, a well established human RCC cell line, was implanted in athymic male mice. Approximately 4 weeks after tumor implant, the mice were treated with oral sunitinib once dairy (sunitinib group) or vehicle only (control group), and tumor volume was calculated. After the treatment, FLT was administered via tail vein and tracer uptake was determined in selected tissues at 1h after injection. The tumors were immunohistochemically assayed for proliferation (PCNA), vascular density (CD34) and apoptosis (TUNEL). Thymidine kinase 1 (TK1) expression of the tumors was also determined with real-time RT-PCR simultaneously. All these parameters of the two groups were compared.

Results There was a significant increase of implanted tumors in control group, while there was a minimal change of the tumors in sunitinib group. The biodistribution study showed a marked reduction of FLT uptake in tumors after 5-day-treatment with sunitinib. Immunohistochemical analysis of the tumors revealed that the changes of FLT uptake were well correlated with those of proliferation, apoptotic status and vascular density. TK1 expression of the tumors was also correlated with FLT uptake.

Conclusions These results of in vivo studies indicate that FLT is a promising tracer in monitoring early therapeutic effects of sunitinib to renal cell carcinoma. FLT PET imaging may have a potential to visualize early-phase changes in proliferation activity of renal cell carcinoma after sunitinib therapy