The response of radiation-induced
fibrosarcoma 1 (RIF-1)
tumors treated with the vascular-disrupting agent (VDA)
ZD6126 was assessed by in vivo and ex vivo 1H magnetic resonance spectroscopy (MRS) methods.
Tumors treated with 200 mg/kg
ZD6126 showed a significant reduction in total
choline (tCho) in vivo 24 hours
after treatment, whereas control
tumors showed a significant increase in tCho. This response was investigated further within both ex vivo unprocessed
tumor tissues and
tumor tissue metabolite extracts. Ex vivo high-resolution magic angle spinning (HRMAS) and 1H MRS of metabolite extracts revealed a significant reduction in
phosphocholine and glycerophosphocholine in biopsies of ZD6126-treated
tumors, confirming in vivo tCho response. ZD6126-induced reduction in
choline compounds is consistent with a reduction in cell membrane turnover associated with
necrosis and cell death following disruption of the
tumor vasculature. In vivo
tumor tissue water diffusion and
lactate measurements showed no significant changes in response to
ZD6126. Spin-spin relaxation times (T2) of water and metabolites also remained unchanged. Noninvasive 1H MRS measurement of tCho in vivo provides a potential
biomarker of
tumor response to VDAs in RIF-1
tumors.