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  • Title: Development of 68Ga-labeled mannosylated human serum albumin (MSA) as a lymph node imaging agent for positron emission tomography.
    Author: Choi JY, Jeong JM, Yoo BC, Kim K, Kim Y, Yang BY, Lee YS, Lee DS, Chung JK, Lee MC.
    Journal: Nucl Med Biol; 2011 Apr; 38(3):371-9. PubMed ID: 21492786.
    Abstract:
    INTRODUCTION: Although many sentinel lymph node (SLN) imaging agents labeled with (99m)Tc 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 (68)Ga. METHODS: A 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 (68)Ga at room temperature. The stability of (68)Ga-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 (68)Ga-NOTA-MSA into a tail vein or a footpad. RESULTS: The 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 (68)Ga-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 (68)Ga-NOTA-MSA showed high liver and spleen uptakes after intravenous injection. (68)Ga-NOTA-MSA injected into a footpad rapidly migrated to the lymph node. CONCLUSIONS: (68)Ga-NOTA-MSA was successfully developed as a novel SLN imaging agent for PET. NOTA-MSA is easily labeled at high efficiency, and subcutaneously administered (68)Ga-NOTA-MSA was found to migrate rapidly to the lymph node.
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