Specific imaging of human brain tumor xenografts utilizing radiolabelled monoclonal antibodies (MAbs).
At the present time, specific imaging and treatment of central nervous system malignancies is not possible. The development of monoclonal hybridoma technology may provide the solution to this problem. We have utilized human glioma-derived cell lines (HGCL) transplanted subcutaneously and intracranially into athymic mice and rats to evaluate the imaging and localizing properties of a panel of MAbs. MAbs 81C6, C12, and D12 and 81C6 Fab have shown significant in vivo localization against HGCL D-54 MG and 81C6 against U-251 MG when compared to equivalent non-specific MAbs. In subcutaneous D-54 MG-induced xenografts, maximal localization indices (LI) of up to 15.0 for 81C6, 6.8 for 81C6 Fab, 6.48 for C12, and 4.47 for D12 have been seen. The tumor-tissue ratios for normal brain have ranged from 235 for 81C6 to 167 for D12. The total percent injected dose for 81C6 was nearly 5% in U-251 MG tumors and 10% of the initial dose in D-54 tumors, while the percent injected dose for control MAb were 1.9% and 2.8%, respectively. Four subcutaneously growing U-251 MG tumors were clearly imaged using 131I-81C6. With intracranially growing D-54 MG, 131I-81C6 provided external imaging of intracranial tumors at sizes as small as 20 mg while 131I-45.6, a non-specific MAb, provided imaging only when tumors achieved sizes greater than 300 mg. These data indicate that operationally specific MAbs and MAb Fab can specifically localize and be used to image human tumors transplanted into immunocompromised animals. The animal models described in this paper provide a sensitive method of evaluating MAbs in pre-human trials.
Bullard, DE; Wikstrand, CJ; Humphrey, PA; Lee, YS; Coleman, RE; Zalutsky, M; Bigner, DD
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