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Cancer Res. 2011 Apr 1;71(7):2428-32. doi: 10.1158/0008-5472.CAN-10-3484. Epub 2011 Mar 29.

Novel human single chain antibody fragments that are rapidly internalizing effectively target epithelioid and sarcomatoid mesotheliomas.

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  • 1Center for Molecular and Functional Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.

Abstract

Human antibodies targeting all subtypes of mesothelioma could be useful to image and treat this deadly disease. Here we report tumor targeting of a novel internalizing human single chain antibody fragment (scFv) labeled with (⁹⁹m)Tc ((⁹⁹m)Tc-M40) in murine models of mesothelioma of both epithelioid (M28) and sarcomatoid (VAMT-1) origins. (⁹⁹m)Tc-M40 was taken up rapidly and specifically by both subtype tumor cells in vitro, with 68% to 92% internalized within 1 hour. The specificity of binding was evidenced by blocking (up to 95%) with 10-fold excess of unlabeled M40. In animal studies, tumors of both subtypes were clearly visualized by SPECT/CT as early as 1 hour postinjection of (⁹⁹m)Tc-M40. Tumor uptake measured as percent of injected dose per gram tissue (%ID/g) at 3 hours was 4.38 and 5.84 for M28 and VAMT-1 tumors, respectively, significantly greater than all organs or tissues studied (liver, 2.62%ID/g; other organs or tissues <1.7%ID/g), except the kidneys (130.7%ID/g), giving tumor-to-blood ratios of 5:1 and 7:1 and tumor-to-muscle ratios of 45:1 and 60:1, for M28 and VAMT-1, respectively. The target-mediated uptake was confirmed by a nearly 70% reduction in tumor activity following administration of 10-fold excess of unlabeled scFv. Taken together, these results indicate that M40 can rapidly and specifically target epithelioid and sarcomatoid tumor cells, demonstrating the potential of this agent as a versatile targeting ligand for imaging and therapy of all subtypes of mesothelioma.

PMID:
21447742
[PubMed - indexed for MEDLINE]
PMCID:
PMC3071798
Free PMC Article

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