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Oncology-Basic Science: Basic ScienceTherapeutic Approaches |
1 Radiology, University of Massachusetts Medical School, Worcester, Massachusetts
66
Objectives: In anticipation of future clinical trial of MORF/cMORF pretargeting with the antiTAG72 antibody CC49, we have investigated its tumor accumulation in mice with varying tumor size, antibody dosage, and timing.
Methods: After conjugating with p-SCN-DTPA and radiolabeling with 111In, the CC49 accumulation in normal organs and tumor was measured in mice bearing tumors between 0.1-1.5 g, at dosages between 10-200 µg, and over a period of up to 4 days. In part to test the ability to obtain the biodistribution results non-invasively, the 3-D images from multipinhole SPECT obtained at 48 h in one mouse were quantitated.
Results: Tumor accumulations increased steadily for 2 days and thereafter decreased slowly in part due to tumor growth. Tumor accumulations decreased with increasing size almost exponentially such that tumor size was the most important determinant. For a tumor of about 1 g, the maximum accumulation was about 20 %ID/g. Neither the percent tumor accumulation nor normal organ accumulations changed over the range of antibody dosage studied. In addition to confirming quantitatively the predominant accumulations of CC49 in tumor and liver, the multipinhole SPECT images clearly showed heterogeneous radioactivity distribution in tumor.
Conclusions: The tumor accumulations of the CC49 antibody were quantitatively described for pretargeting prediction. This antibody may therefore be considered for future clinical pretargeting applications.
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