Optimal timing of administration of hyperthermia in combined radioimmunotherapy

Local hyperthermia (HT) may enhance the efficacy of radioimmunotherapy (RIT ). However, the optimal timing of HT relative to administration of antibody is unknown. Human colon cancer xenografts (290 +/- 25 mm(3)) were treated with 4.63 MBq I-131-A7 monoclonal antibody (MAb) anti-Mr 45,000 glycoprotei n antigen on colorectal cancer, and HT at 43 degrees C for 1 h was administ ered at. (A), 2 days after the I-131-A7 injection at the maximum I-131-A7 t umor accumulation (radiation); (B), soon after the I-131-A7 injection aimin g to increase the tumor accumulation of I-131-A7 die to HT vascular effects ; or (C), 2 days before the I-131-A7 injection in an attempt at injecting I -131-A7 when increased antigen expression could be expected Specific growth delay (SGD) of tumors was calculated as (Tq(treat)-Tq(control))/Tq(control ) where Tq was tumor quadrupling time. The biodistribution and intratumoral distribution of I-131-A7 were investigated to explore the mechanism of tum or response among the different HT regimens. HT alone produced some antitum or effect (SGD 1.90 +/- 0.26), which was less effective than RIT (3.11 +/- 0.50). HT soon after I-131-A7 RIT (B) significantly enhanced RIT efficacy ( 6.57 +/- 0.51, p < 0.0001) whereas neither MT at 2 days after RIT (A) nov a t 2 days before RIT (C) did so. Biodistribution study revealed that HT soon after RIT (B) increased the tumor radiation absorbed dose by a factor of 2 .4, while HT after RIT (A) did not increase radiation dose and HT before RI T (C) decreased it. Radioluminograms of tumor sections indicated that HT so on after RIT (B) improved the uniformity of I-131-A7 distribution whereas H T after RIT (A) did nor and HT before RIT (C) diminished the uniformity of A7 distribution. In conclusion, the best therapeutic efficacy was obtained when HT was combined soon after the initiation of RIT with I-131-A7 The inc reased tumor radiation absorbed dose and the uniform intratumoral distribut ion of I-131-A7 were important factors underlying this improvement, and the additive cytotoxicity of HT is suspected to some extent. MT-induced radios ensitization of tumor was not apparent in this model when HT was given 2 da ys after I-131-A7 MAb.