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SPECT Quantitation of Cobalt-57-Bleomycin to Predict Treatment Response and Outcome of Patients with Lung Cancer

Departments of Nuclear Medicine and Oncology, Rambam Medical Center
Faculty of Medicine and the B. Rappaport Research Institute, Technion—Israel Institute of Technology, Haifa, Israel

Correspondence: For correspondence or reprints contact: Dov Front, MD, PhD, Dept. of Nuclear Medicine, Rambam Medical Center, Haifa 35254, Israel.

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. Methods: 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. Results: 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). Conclusions: 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.

Key Words: cobalt-57-bleomycin • SPECT • DNA • lung cancer