Development and evaluation of a Ga-68 labeled pamoic acid derivative for in vivo visualization of necrosis using positron emission tomography

作者：Prinsen Kristof^*; Li Junjie; Vanbilloen Hubert; Vermaelen Peter; Devos Ellen; Mortelmans Luc; Bormans Guy; Ni Yicheng; Verbruggen Alfons

来源：Bioorganic & Medicinal Chemistry, 2010, 18(14): 5274-5281.

DOI：10.1016/j.bmc.2010.05.050

• Cell death
• Necrosis
• Gallium-68
• PET

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 Ga-68-bis-DTPA-PA as a potential tracer for in vivo visualization of necrosis by positron emission tomography (PET). Radio-labeling was achieved with a decay-corrected radiochemical yield of 63%. Biodistribution and in vivo stability studies in normal mice showed that Ga-68-bis-DTPA-PA is cleared faster from normal tissue than the previously reported Tc-99m(CO)3 complex with bis-DTPA-PA which on the other hand is more stable in vivo. Ga-68-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 Ga-68-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, Ga-68-bis-DTPA- PA showed a faster and higher uptake in necrotic tissue than the 99mTc(CO) 3 analog. These results show that Ga-68-bis-DTPA-PA specifically binds to necrotic tissue and is a promising tracer for in vivo visualization of necrosis using PET.

• 出版日期2010-7-15