Marked survival prolongation of mice bearing a transplantable colon adenocarcinoma by treatment with radioactive platinum-[125I]histamine complex. Preliminary report.
BACKGROUND
Recently, a new PtCl2-histamine complex, and its radioactive analogues labelled with I-131 and I-125 have been synthesised and investigated both in vitro and in vivo. In this preliminary report the survival rate of radioactive platinum-[125I] histamine therapy in tumour-bearing mice is demonstrated.


METHODS
A murine model of transplantable colon adenocarcinoma (C38) in C57BL/6 mice (15 days postimplantation) was used for the experiment. Three groups of animals were treated every 2-3 days with five intraperitoneal injections of the following preparations: PtCl2Hist (total dose of Pt--125 micromol/kg), PtCl2[125I]Hist (total dose of I-125--4.2 MBq; Pt--13 micromol/kg), and "Active/Cold"--PtCl2[125I]Hist/PtCl2Hist (I-125--4.2 MBq; Pt--125 micromol/kg). A solution of 15% dimethylformamide in saline was applied to the control group. A survival analysis with the Kaplan-Meier estimation of survival curves and a statistical comparison by a log-rank test was applied to evaluate the anticancer activity of the tested preparations.


RESULTS
Treatment of the animals with platinum-histamine preparations resulted in a significant prolongation of survivals, especially if the radioactive complex with carrier-added PtCl2Hist (p < 0.005) was applied. The highest, almost a 60% prolongation of survival was observed in the Active/Cold group (MStr/MScon ratio = 1.58, 95% CI 1.22-1.93). For this group there was the lowest risk of death (hazard ratio HR = 0.29), whereas HR = 0.45 and 0.47 were found in the animals treated with unattended PtCl2Hist and 125I-labelled complex, respectively.


CONCLUSIONS
The significant enhancement of in vivo anti-cancer activity by a concomitant combination of the therapeutic factors, i.e. cytotoxic/cytostatic activity of the platinum(II)-histamine and the Auger electrons effects generated by the attached I-125 radionuclide, was found on the murine model of transplantable colon adenocarcinoma.
Garnuszek
Piotr
P
Department of Radiopharmaceuticals, The National Institute of Public Health, Warsaw, Poland. pg@il.waw.pl
D000230:Adenocarcinoma / Q000532:radiotherapy*; D000818:Animals; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D006632:Histamine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010865:Pilot Projects; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D013534:Survival; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome
C455111:(iodohistamine)platinum(II); D007457:Iodine Radioisotopes; D009944:Organoplatinum Compounds; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; D006632:Histamine