Indium-111-bleomycin complex in squamous cell cancer xenograft tumors of nude mice.
BACKGROUND
Labeling of bleomycin with Auger-emitter Indium-111 increases cytotoxicity in squamous cell cancer (SCC) cell lines, as we have reported earlier. In this study, we investigated whether (111)In- BLMC is toxic and effective in vivo among SCC-xenografted mice. The influence of (111)InBLMC on the squamous cell carcinoma cell cycle stimulated interest.


METHODS
In an animal experiment, 10 SCC-xenografted mice were used, two for demonstrating targeting in gamma-camera images, eight for intraperitoneally receiving NaCl, BLM, or (111)InBLMC as therapy. After a 2-week follow-up, the tumors were analyzed for proliferation (mitoses, Ki-67). DNA flow cytometric analysis was carried out from tumor samples and three UT-SCC cell lines.


RESULTS
Tumors were observed on gamma-camera images in xenografted mice after a (111)InBLMC injection. The UT-SCC-19A-xenografted mouse had a T/non-T uptake of 7.54 at 4 hours after the injection. At the end of the therapeutic trial, the mice were alive. In spite of a small number of animals, our findings indicate that BLM and (111)InBLMC seem to be more effective than NaCl in reducing tumor size. The proliferative activity was strong in BLM and in (111)InBLMC groups, indicating regrowth of the tumors. In DNA analysis, the percentages of cells in the G2/M-phases increased after exposure to BLM and particularly to (111)InBLMC in all three cell lines.


CONCLUSIONS
The effect of BLM is preserved after the adding of Auger-emitter In-111. Tumor-seeking (111)InBLMC can be administered safely at tumor-decreasing concentrations in xenograft head and neck cancers. To demonstrate the antitumor effect of (111)InBLMC, the experiments should be extended to include a larger number of mice. BLM, and especially (111)InBLMC, seems to induce alteration in the cell cycle by producing a G2/M block. The verification of the result requires repeated in vitro experiments.
Jääskelä-Saari
Hilkka A
HA
Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Grénman
Reidar
R
Ramsay
Hans A
HA
Tarkkanen
Jussi
J
Paavonen
Timo
T
Kairemo
Kalevi J A
KJ
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use*; D001835:Body Weight; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D004247:DNA / Q000737:chemistry; D005434:Flow Cytometry; D015902:Gamma Cameras; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D007205:Indium Radioisotopes; D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; D001761:Bleomycin; D004247:DNA