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Saturday, February 16, 2013 11:05:00 PM
Use of 89Zr-ImmunoPET successful for imaging of drug-induced apoptosis in tumor treatment targeting phosphatidylserine
A recent issue of ‘Nuclear Medicine and Biology’ reports the positive results of a research to test the potential of ImmunoPET with 89Zr for visualizing the occurrence of apoptosis following tumor treatment with pro-apoptotic drugs. In this study [1], carried out by A. Ogasawara and her colleagues at Genentech, Inc. (USA), PGN635, a monoclonal antibody (mAb) targeting phosphatidylserine, was labeled with 89Zr and tested in animal models of human cancer, treated with pro-apoptotic therapy. The resulting probe, 89Zr-PGN635, was assessed at pre-clinical phase in four tumor xenograft models, one of which evaluated the effect of paclitaxel treatment in triggering the intrinsic apoptotic pathway, whereas the others examined the effects of treatment using an agonistic death-receptor mAb in activating the extrinsic apoptotic pathway.
The results of the study could confirm the hypothesis that the relatively long plasma half-life achieved by a residualizing radionuclide, once attached to a full-length antibody, would permit the timely visualization of apoptosis induced by the drug treatment, following specific accumulation of the probe in apoptotic tumor tissue. Indeed, high accumulation of the 89Zr-PGN635 probe could be detected in treated tumors undergoing apoptosis (30 %ID/g), as well as high tumor-to-blood ratios (up to 13 times as high). In comparison, control groups receiving vehicle or imaged with a non-binding antibody probe presented significantly lower tumor uptake.
In conclusion, it could be confirmed that radiolabeled mAbs binding to intracellular targets, transiently exposed on the cell surface during apoptosis, is a successful option for detection of tumor response to therapy. Based on this principle, new radionuclide-mAb combinations may be developed to meet the demands of specific types of cancer.
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