Experimental radioimmunotherapy with 186Re-MAG3-A7 anti-colorectal cancer monoclonal antibody: comparison with 131I-counterpart.

A murine IgG1 against a Mr 45 kD tumor-associated glycoprotein in human colorectal cancer, A7, was radiolabeled with 186Re by a chelating method with a mercaptoacetyltriglycine (MAG3). Its specific activity was 119 MBq/mg, which would be high enough for a therapeutic purpose, and its immunoreactivity was preserved well as was 131I-A7 labeled by the chloramine-T method. Growth of human colon cancer xenografts, 9.14 +/- 0.44 mm in diameter, in nude mice was significantly suppressed by an intravenous dose of 4.48 MBq of 186Re-A7. The therapeutic outcome with 186Re-A7 was better than that with 4.63 MBq of 131I-A7. Toxicity of treatments assessed by body weight change was similar with both conjugates. These results are likely caused by the tumor size and more favorable physical properties of 186Re than those of 131I.

Methylxanthine sensitization of human colon cancer cells to 186Re-labeled monoclonal antibody.

UNLABELLED: Tumor cells lacking the functional p53 suppressor gene may arrest at the G2 phase of the cell cycle after exposure to ionizing radiation, resulting in increased radioresistance. Methylxanthines (MTXs), such as pentoxifylline (PTX) or caffeine (CAF), can inhibit the G2-phase checkpoint arrest of damaged cells and thus radiosensitize them. However, the effect of MTX in cells irradiated with low-dose-rate beta-emission is not well understood. METHODS: A clonogenic assay was performed with LS180 human colon cancer cells lacking the functional p53 suppressor gene. Cells were irradiated with increasing concentrations of 186Re-mercaptoacetyltriglycine (186Re-MAG3)-labeled A7 monoclonal antibody against colorectal cancer (0-925 kBq/mL) at 37 degrees C in 5% CO2 for 24 h in the presence or absence of PTX (0-2 mmol/L) or CAF (0-5 mmol/L). The enhancement ratio (ER) with MTX was calculated as a ratio of 50% cell-killing concentration of 186Re-MAG3-A7 in control cells to that in cells treated with PTX or CAF. The cell cycle distribution was analyzed with a flow cytometer. RESULTS: The concentration of 50% cell kill was 474 kBq/mL 186Re-MAG3-A7. Both PTX and CAF dose dependently enhanced the cytotoxicity of 186Re-MAG3-A7: ERs of 0.5 mmol/L PTX, 2 mmol/L PTX, 1 mmol/L CAF, and 5 mmol/L CAF were 1.50, 2.18, 1.54, and 2.63, respectively. Flow cytometry showed that the percentage nonirradiated cells in the G2/M phase of the cell cycle was 11.3% +/- 1.66%. On the other hand, cells exposed to 186Re-MAG3-A7 accumulated in the G2/M phase of the cell cycle (40.2% +/- 1.46%), which was inhibited by the presence of 1 mmol/L PTX (19.8% +/- 8.12%) or 2 mmol/L CAF (26.9% +/- 6.21%). CONCLUSION: Cellular modulation of the cell cycle with PTX and CAF radiosensitized LS180 colon cancer cells exposed to 186Re radiation.

Absolute measurement of 166mHo radioactivity and development of sealed sources for standardization of gamma-ray emitting nuclides

Holmium-166m has a long half life (1200 yr) and emits a large number of gamma-rays between 80 and 1400 keV. These characteristics are very suitable for gamma-ray calibration sources, therefore, the absolute activity of 166mHo was measured and several sealed sources were produced to be used as reference sources for the secondary standardization systems for gamma-ray emitting nuclides. In this project, seven metal sealed sources and ten point sources were produced and several of these sources were transferred to the secondary standard laboratories to complete the traceability scheme.