Development of 68Ga-labeled mannosylated human serum albumin (MSA) as a lymph node imaging agent for positron emission tomography

IntroductionAlthough many sentinel lymph node (SLN) imaging agents labeled with 99mTc have been developed, no positron-emitting agent has been specifically designed for SLN imaging. Furthermore, the development of the beta probe and the requirement for better image resolution have increased the need for a positron-emitting SLN imaging agent. Here, we describe the development of a novel positron-emitting SLN imaging agent labeled with 68Ga.MethodsA mannosylated human serum albumin (MSA) was synthesized by conjugating α-d-mannopyranosylphenyl isothiocyanate to human serum albumin in sodium carbonate buffer (pH 9.5), and then 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid was conjugated to synthesize NOTA-MSA. Numbers of mannose and NOTA units conjugated in NOTA-MSA were determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. NOTA-MSA was labeled with 68Ga at room temperature. The stability of 68Ga-NOTA-MSA was checked in labeling medium at room temperature and in human serum at 37°C. Biodistribution in normal ICR mice was investigated after tail vein injection, and micro-positron emission tomography (PET) images were obtained after injecting 68Ga-NOTA-MSA into a tail vein or a footpad.ResultsThe numbers of conjugated α-d-mannopyranosylphenyl isothiocyanate and 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid units in NOTA-MSA were 10.6 and 6.6, respectively. The labeling efficiency of 68Ga-NOTA-MSA was greater than 99% at room temperature, and its stability was greater than 99% at 4 h. Biodistribution and micro-PET studies of 68Ga-NOTA-MSA showed high liver and spleen uptakes after intravenous injection. 68Ga-NOTA-MSA injected into a footpad rapidly migrated to the lymph node.Conclusions68Ga-NOTA-MSA was successfully developed as a novel SLN imaging agent for PET. NOTA-MSA is easily labeled at high efficiency, and subcutaneously administered 68Ga-NOTA-MSA was found to migrate rapidly to the lymph node.