Development and evaluation of a 68Ga labeled Pamoic acid (cas 130-85-8) derivative for in vivo visualization of necrosis using positron emission tomography

Add time:09/29/2019    Source:infona.pl

In this study, we labeled N,N′-bis(diethylenetriamine pentaacetic acid)-Pamoic acid (cas 130-85-8) bis-hydrazide (bis-DTPA-PA) with the generator produced PET radionuclide gallium-68 and evaluated 68 Ga-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 68 Ga-bis-DTPA-PA is cleared faster from normal tissue than the previously reported 99m Tc(CO) 3 complex with bis-DTPA-PA which on the other hand is more stable in vivo. 68 Ga-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 68 Ga-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, 68 Ga-bis-DTPA-PA showed a faster and higher uptake in necrotic tissue than the 99m Tc(CO) 3 analog. These results show that 68 Ga-bis-DTPA-PA specifically binds to necrotic tissue and is a promising tracer for in vivo visualization of necrosis using PET.

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