Imaging apoptosis in vivo using 124I-annexin V and PET.
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 (124)I-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 (124)I. We report the validation of (124)I-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 (124)I-annexin V and the correlation of (124)I-annexin V uptake with apoptotic density (AD). Sixfold more (124)I-annexin V was associated with Jurkat cells after apoptosis induction, indicating that PS binding by annexin V was preserved after iodination. (124)I-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 (124)I-annexin V but not (124)I-ovalbumin in apoptotic liver lesions. In vivo (124)I-annexin V uptake, derived from PET images, correlated with histologically derived AD (r=.86, P<.01). These results demonstrate that (124)I-annexin V is localised to anti-Fas-induced apoptosis, in contrast to (124)I-ovalbumin, which did not show preferential uptake in the apoptotic liver.
Keen
Heather G
HG
Cancer Research UK Department of Radiochemical Targeting and Imaging, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, M20 4BX Manchester, UK.
Dekker
Bronwen A
BA
Disley
Lynn
L
Hastings
David
D
Lyons
Steve
S
Reader
Andrew J
AJ
Ottewell
Penny
P
Watson
Alastair
A
Zweit
Jamal
J
D000818:Animals; D017304:Annexin A5 / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000502:physiology*; D022781:Hepatocytes / Q000000981:diagnostic imaging* / Q000473:pathology / Q000502:physiology*; D007457:Iodine Radioisotopes; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology / Q000502:physiology*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
D017304:Annexin A5; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals