Published in Cancer Detection and Prevention 1995; 19(1).

Radiochemotherapy in head and neck cancer using In-111-BLMC

KJA Kairemo, H Ramsay, T Paavonen, H Jaaskela-Saari, M Tagesson, K Ljunggren, S-E Strand

Clin Chem, Otol, Pathol, Helsinki Univ., Finland; Radiate Phys, Lund, Sweden.

Bleomycin (BLM, 13 alkaline glycopeptides), a natural antibiotic toxic to dividing cells (G(2)/M-specific), has been used successfully for treatment of H&N cancer. Combining radio- and chemotherapy using BLM complex (BMLC) is a fascinating possibility. In-111-BLMC was prepared at low pH. In-111-BLMC (subfractions A(2a-c)) (100 MBq/mg) were administered to H&N cancer patients in escalating doses of 75 MBq, 175 MBqand 375 MBq. Scintigraphic data were compared with tissue samples from surgery 48 h after injection. SPECT studies were also performed in 3-D format for MRI-fusion imaging. T(1/2) for radioactivity was 1.5-3.1 h in serum and 1.4-3.7 h in urine. About 50% of the activity was excreted in urine within 3 h, and >95% within 22 h. Tumor uptake varied 0.39 to 0.95xl0(-3) %/ID/g (at 48 h). Kidneys were the critical organ; the estimate for a 3700 MBq dose, assuming a MRT of 5 h, was 2.2 Gy (tolerance 20 Gy). The tumor dose was 0.66 cGy/MBq, when assuming a MRT of 16 h, in a 14-gram tumor (MIRD formalism), tumor T(1/2):s were 16-49 h. The activity distribution and penetration into tumor tissue was not affected by the increasing injected activity. BLMC uptake was directly proportional to Ki-67 and Mib activity in tissues and the number of mitoses. Autoradiography and beta camera revealed mainly cell nuclear localization and non-uniform distribution of activity. These data are compatible with In-111-BLMC being a suitable radiopharmaceutical for adjuvant Auger-electron therapy (using In-114m)of H&N cancer.

Paper presented at the International Symposium on the Impact of Biotechnology on Predictive Oncology and Therapy; Boston, Massachusetts; December 11 - 13, 1994; in the section on Diagnostic Markers.