Effects of hyperthermia and iodine-131-labeled anticarcinoembryonic antigen monoclonal antibody on human tumor xenografts in nude mice.

BACKGROUND: Many studies have demonstrated synergistic interaction between hyperthermia and radiation. This study was undertaken to determine whether hyperthermia could enhance the effect of radioimmunotherapy (RIT) in the treatment of human colon adenocarcinoma xenografts in nude mice. METHODS: The experiments were conducted in two parts. During the first part of the study, preliminary information was obtained regarding the effect of various temperatures (41 degrees C, 42 degrees C, and 43 degrees C for 45 minutes) and iodine-131-labeled anticarcinoembryonic antigen (CEA) monoclonal antibodies (RMoAb) with administered activity ranging from 130 +/- 19 microCi to 546 +/- 19 microCi on tumor regrowth delay (TRD) and volume doubling time. This information was used in Part 2 of the study, which included four groups of mice: (1) a control group, (2) a group treated with hyperthermia, (3) a group treated with RMoAb, and (4) a group treated with a combination of RMoAb and hyperthermia. RESULTS: Maximum and significantly increased TRD was observed in the group treated with RMoAb and hyperthermia (slope, 0.057) compared with the control group (slope, 0.322), the hyperthermia-treated group (slope, 0.302), and the group treated with RMoAb alone (slope, 0.098). The ratio of the slopes between the groups treated with RMoAb and those treated with RMoAb and hyperthermia was 1.72. No correlation was detected between the percent of antibody uptake in the tumor and tumor regression in the groups treated with heat and RMoAb and those treated with RMoAb alone. CONCLUSIONS: The results of these experiments show that hyperthermia increased the effectiveness of iodine-131-labeled anti-CEA monoclonal antibodies against human colon carcinoma xenografts in nude mice. This study offers a rationale for combining hyperthermia and low-dose radiation produced from RIT in clinical practice.

Stability of radioiodinated monoclonal antibodies: in vitro storage and plasma analysis.

The in vitro stability and immunointegrity of four radioiodinated monoclonal antibodies was evaluated in various storage conditions and also in plasma samples. The monoclonal antibodies studied included T101, B72.3, Lym1, and 16.88. Stabilities of typical monoclonal antibody therapy solutions, with radioactivities ranging from 2220 to 3700 MBq (60-100 mCi) were assessed using conventional instant thin layer chromatography and size exclusion high performance liquid chromatography. Radioimmunoreactivity was assessed using a live cell attenuated cell, or mucin-linked bead assay. Results of the study demonstrated that therapy solutions were stable to degradation, if properly stored in 5 or 10% human serum albumin at 4 degrees C for the duration of the study (5 days). Minor losses in immunoreactivity were also measured in stabilized therapy solutions. When incubated in plasma samples, radioiodinated monoclonal antibodies generally remained stable for the duration of the study (3 days). However, significant decreases in immunoreactivity were measured for specific radioiodinated monoclonal antibody preparations.