SPECT QUANTITATION OF COBALT-57-BLEOMYCIN TO PREDICT TREATMENT RESPONSE AND OUTCOME OF PATIENTS WITH LUNG-CANCER

Our hypothesis is that the concentration of Co-57-bleomycin (Cobleo) i n lung tumors reflects tumor cell kinetics and thus, prognosis. The re lationship between the tumor concentration of Cobleo measured in vivo by quantitative SPECT, response to chemotherapy and survival was inves tigated. Methods: Twenty patients with small-cell lung carcinoma (SOLO ) and 49 patients with non-small-cell lung carcinoma (NSCLC) were stud ied. 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 muri ne tumor model and in samples of eight human tumors. Results: Tumors t hat 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 SOLO and 2.72% ID/cc 10(-3) for NSCLC were found to best separate patien ts into short- and long-term survival groups. In the EMT6 murine tumor model, a good correlation was found between the concentration of Co-b leo 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 S PECT (r = 0.85). Conclusions: SPECT-measured Co-bleo concentration pre dicts the response to treatment and the outcome in patients with lung tumor by showing Co-bleo binding to DNA and tumor cell kinetics.