title: Development and evaluation of a 68Ga labeled pamoic acid derivative for in vivo visualization of necrosis using positron emission tomography.
abstract: In this study, we labeled N,N'-bis(diethylenetriamine pentaacetic acid)-pamoic acid bis-hydrazide (bis-DTPA-PA) with the generator produced PET radionuclide gallium-68 and evaluated 68Ga-bis-DTPA-PA as a potential tracer for in vivo visualization of necrosis by positron emission tomography (PET). Radiolabeling was achieved with a decay-corrected radiochemical yield of 63%. Biodistribution and in vivo stability studies in normal mice showed that 68Ga-bis-DTPA-PA is cleared faster from normal tissue than the previously reported 99mTc(CO)3 complex with bis-DTPA-PA which on the other hand is more stable in vivo. 68Ga-bis-DTPA-PA showed a 3.5-5 times higher binding to necrotic tissue than to viable tissue as shown by in vitro autoradiography while no statistically significant increased hepatic uptake was found in a biodistribution study in a mouse model of hepatic apoptosis. Specificity and avidity for necrosis was further evaluated in rats with a reperfused partial liver infarction and ethanol induced muscular necrosis. Dynamic microPET images showed a fast and prolonged uptake of 68Ga-bis-DTPA-PA in necrotic tissue with in vivo and ex vivo images correlating well with histochemical stainings. With necrotic to viable tissue activity ratios of 8-15 on ex vivo autoradiography, depending on the necrosis model, 68Ga-bis-DTPA-PA showed a faster and higher uptake in necrotic tissue than the 99mTc(CO)3 analog. These results show that 68Ga-bis-DTPA-PA specifically binds to necrotic tissue and is a promising tracer for in vivo visualization of necrosis using PET.
authors.affiliation: Laboratory for Radiopharmacy, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, and Department of Radiology, University Hospital Gasthuisberg, Herestraat 49, Box 821, BE-3000 Leuven, Belgium. kristof.prinsen@pharm.kuleuven.be
authors.forename: Kristof
authors.initials: K
authors.lastname: Prinsen
authors.forename: Junjie
authors.initials: J
authors.lastname: Li
authors.forename: Hubert
authors.initials: H
authors.lastname: Vanbilloen
authors.forename: Peter
authors.initials: P
authors.lastname: Vermaelen
authors.forename: Ellen
authors.initials: E
authors.lastname: Devos
authors.forename: Luc
authors.initials: L
authors.lastname: Mortelmans
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
mesh_terms: D000818:Animals; D001345:Autoradiography; D005710:Gallium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007238:Infarction / Q000000981:diagnostic imaging; D008099:Liver / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D009284:Naphthols / Q000737:chemistry / Q000493:pharmacokinetics*; D009336:Necrosis / Q000000981:diagnostic imaging*; D004369:Pentetic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005710:Gallium Radioisotopes; D009284:Naphthols; D004369:Pentetic Acid; C004368:pamoic acid