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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.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Prinsen K,Li J,Vanbilloen H,Vermaelen P,Devos E,Mortelmans L,Bormans G,Ni Y,Verbruggen A

doi

10.1016/j.bmc.2010.05.050

subject

Has Abstract

pub_date

2010-07-15 00:00:00

pages

5274-81

issue

14

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(10)00481-5

journal_volume

18

pub_type

杂志文章

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