SPECT quantitation of cobalt-57-bleomycin to predict treatment response and outcome of patients with lung cancer.

Abstract

Our hypothesis is that the concentration of 57Co-bleomycin (Co-bleo) in lung tumors reflects tumor cell kinetics and thus, prognosis. The relationship between the tumor concentration of Co-bleo measured in vivo by quantitative SPECT, response to chemotherapy and survival was investigated. Twenty patients with small-cell lung carcinoma (SCLC) and 49 patients with non-small-cell lung carcinoma (NSCLC) were studied. The concentration of Co-bleo was measured by SPECT in vivo in the tumor. The correlation between Co-bleo concentration in the tumor and the fraction of Co-bleo bound to DNA was investigated in an EMT6 murine tumor model and in samples of eight human tumors. Tumors that did not respond to treatment showed a significantly higher Co-bleo concentration 8 hr after injection than tumors that responded (5.83% +/- 1.97% ID/cc * 10(-3) versus 2.55% +/- 1.23% ID/cc * 10(-3), p < 0.001). Values of Co-bleo concentration of 2.97% ID/cc * 10(-3) for SCLC and 2.72% ID/cc * 10(-3) for NSCLC were found to best separate patients into short- and long-term survival groups. In the EMT6 murine tumor model, a good correlation was found between the concentration of Co-bleo in the tumor and the fraction of Co-bleo bound to DNA (r = 0.75). In human tumor samples, a good correlation was found between DNA-bound Co-bleo measured in vitro and the concentration measured in vivo by SPECT (r = 0.85). SPECT-measured Co-bleo concentration predicts the response to treatment and the outcome in patients with lung tumor by showing Co-bleo binding to DNA and tumor cell kinetics.