Direct dose confirmation of quantitative autoradiography with micro-TLD measurements for radioimmunotherapy.

Autoradiography has shown marked heterogeneous distribution of radioactivity in all ten radiolabeled monoclonal antibody/tumor combinations evaluated by our laboratories for radioimmunotherapy (RIT) in mice. Quantitative autoradiography was performed on two of these combinations (131I-B72.3/colorectal carcinoma and 131I-LYM-1/Raji B-cell lymphoma) to obtain a correlation of film density with radiolabeled antibody distribution. Through the use of sectioned mini-thermoluminescent dosimeter(s) (TLD) or micro-TLD, isodose curves were generated from the film gradient density lines. A computer program was written to compare theoretical absorbed dose calculations to measured micro-TLD values. First-order agreement was reached for both antibody/tumor systems: (a) B72.3/colorectal system--810 cGy measured/824 cGy calculated per 200 microCi injected and (b) LYM-1/lymphoma system--1,740 cGy measured/1,580 cGy calculated per 656 microCi injected (1 cGy = 1 rad). Additionally, the measured absorbed dose heterogeneity over a 500-micron length of up to 400% which suggests that the use of quantitative autoradiography is necessary in order to correctly determine the underlying radiobiological effects of RIT. Theoretical computer modeling based on similar autoradiographic activity distributions has also provided a convenient means of assessing absorbed dose variation patterns from other radiolabels such as 90Y.

Pharmacokinetics of the monoclonal antibody B72.3 and its fragments labeled with either 125I or 111In.

A comparison of the pharmacokinetics of intact B72.3 (a murine monoclonal antibody specific for human breast and colon carcinoma) with F(ab')2 and Fab fragments labeled with 111In and 125I was done in athymic mice bearing target (LS174T) and non-target (HCT-15) tumors. IgG B72.3 labeled with either isotype imaged LS174T. Biodistributions of both labels were similar in all organs except liver. F(ab')2 also imaged the LS174T tumor, while Fab bearing either isotype did not. The blood clearance was Fab greater than F(ab')2 greater than immunoglobulin G B72.3 for both isotopes. 111In-labeled fragments yielded large accumulations in the kidneys which persisted for 2 days. The different patterns of biodistribution for the various forms of B72.3 labeled with the two isotopes suggest that the most desirable combination of fragment and isotope will depend on the intended use.

Site-related differences in the localization of the monoclonal antibody OX7 in SL2 and SL1 lymphomas.

The uptake of a monoclonal antibody (OX7) by murine lymphomas (SL1, SL2) growing in two sites in the mouse were compared. SL2 tumors grown in the subrenal site showed greater specific antibody uptake than did the same tumor grown in the subcutaneous site. Major differences in membrane bound antibody, in vitro antibody binding patterns, and gamma scintillation camera imaging were also observed between the two sites. These differences may be due to the greater blood flow measured in tumors growing in the subrenal capsule than those growing at the subcutaneous site. The differences observed in antibody uptake of the same tumor growing in two different sites raises questions concerning the choice of animal model systems that can be used to predict clinical utility.