Imaging apoptosis in vivo using 124I-ANNEXIN V (cas 136107-94-3) and PET

Add time:09/06/2019    Source:sciencedirect.com

Abnormal regulation of apoptosis is an important pathogenic mechanism in many diseases including cancer. Techniques to assess apoptosis in living organisms are limited and, in the case of solid organs, restricted to histological examination of biopsy samples. We investigated the use of 124I-annexin V, which binds to phosphatidylserine (PS) on the surface of apoptotic cells, as a potential positron emission tomography (PET) radioligand for the noninvasive measurement of apoptosis in vivo. Annexin V and a similar-sized protein, ovalbumin, were directly labelled with 124I. We report the validation of 124I-annexin V in vitro and in an animal model of liver apoptosis that has not previously been used to test iodinated annexin V. Also, for the first time, we report metabolite analysis of 124I-annexin V and the correlation of 124I-annexin V uptake with apoptotic density (AD). Sixfold more 124I-annexin V was associated with Jurkat cells after apoptosis induction, indicating that PS binding by annexin V was preserved after iodination. 124I-ovalbumin did not demonstrate increased uptake in apoptotic cells. In normal BDF-1 mice, the radioligand was rapidly cleared, but some in vivo dehalogenation resulted in the accumulation of activity in the thyroid and stomach content. PET images demonstrated uptake of 124I-annexin V but not 124I-ovalbumin in apoptotic liver lesions. In vivo 124I-annexin V uptake, derived from PET images, correlated with histologically derived AD (r=.86, P<.01). These results demonstrate that 124I-annexin V is localised to anti-Fas-induced apoptosis, in contrast to 124I-ovalbumin, which did not show preferential uptake in the apoptotic liver.

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