Nuclear medicine communications · 2004
Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging.
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Jeong Jae Min, Hong Mee Kyung, Kim Young Joo, Lee Jaetae, Kang Joo Hyun, Lee Dong Soo, Chung June-Key, Lee Myung Chul
Аннотация
BACKGROUND AND AIM: Various mannose receptor-binding agents, for example 99mTc-diethylenetriaminepentaacetic acid (DTPA)-mannosyl-polymer, have been developed for sentinel lymph node (SLN) imaging. In order to simplify the synthesis and labelling procedure and to improve the biological properties, we developed a novel mannose receptor-binding agent, 99mTc-neomannosyl human serum albumin (99mTc-MSA), for SLN imaging.
METHODS: MSA was synthesized by conjugating mannopyranosylphenylisothiocyanate to human serum albumin (HSA). After reducing MSA with beta-mercaptoethanol and PD-10 column purification, a medronate solution containing stannous fluoride was added, divided into aliquots and freeze-dried. Reduced MSA was labelled with 99mTc-pertechnetate solution. The stability was checked for 24 h at 37 degrees C in human serum. The biodistribution of 99mTc-MSA in mice was investigated by intravenous injection through the tail vein and subcutaneous injection into the foot pad. The biodistributions of 99mTc-HSA and 99mTc-antimony sulphur colloid (99mTc-ASC) were also investigated for comparison. Dynamic whole-body images were obtained for 30 min after subcutaneous injection into the rats' foot pads.
RESULTS: The number of mannose molecules conjugated per MSA was 15.9. The number of thiol groups produced was 19.4 per MSA after reduction with beta-mercaptoethanol. Labelling yields were always higher than 97%. 99mTc-MSA was stable for 24 h at 37 degrees C in human serum. The biodistribution in mice after intravenous injection showed high liver uptake (50.7+/-5.5% and 42.7+/-3.7% injected dose per gram at 10 and 60 min, respectively). 99mTc-MSA and 99mTc-ASC showed high accumulation in the lymph nodes after subcutaneous injection, whereas 99mTc-HSA and Tc-tin colloid did not, in both biodistribution and imaging studies.
CONCLUSIONS: We have successfully developed a novel 99mTc-MSA for lymphoscintigraphy. The results of animal studies show that 99mTc-MSA has promising properties for SLN imaging.
METHODS: MSA was synthesized by conjugating mannopyranosylphenylisothiocyanate to human serum albumin (HSA). After reducing MSA with beta-mercaptoethanol and PD-10 column purification, a medronate solution containing stannous fluoride was added, divided into aliquots and freeze-dried. Reduced MSA was labelled with 99mTc-pertechnetate solution. The stability was checked for 24 h at 37 degrees C in human serum. The biodistribution of 99mTc-MSA in mice was investigated by intravenous injection through the tail vein and subcutaneous injection into the foot pad. The biodistributions of 99mTc-HSA and 99mTc-antimony sulphur colloid (99mTc-ASC) were also investigated for comparison. Dynamic whole-body images were obtained for 30 min after subcutaneous injection into the rats' foot pads.
RESULTS: The number of mannose molecules conjugated per MSA was 15.9. The number of thiol groups produced was 19.4 per MSA after reduction with beta-mercaptoethanol. Labelling yields were always higher than 97%. 99mTc-MSA was stable for 24 h at 37 degrees C in human serum. The biodistribution in mice after intravenous injection showed high liver uptake (50.7+/-5.5% and 42.7+/-3.7% injected dose per gram at 10 and 60 min, respectively). 99mTc-MSA and 99mTc-ASC showed high accumulation in the lymph nodes after subcutaneous injection, whereas 99mTc-HSA and Tc-tin colloid did not, in both biodistribution and imaging studies.
CONCLUSIONS: We have successfully developed a novel 99mTc-MSA for lymphoscintigraphy. The results of animal studies show that 99mTc-MSA has promising properties for SLN imaging.
Предметные рубрики MeSH
AnimalsAntimonyHumansIsothiocyanatesLymph NodesLysineMaleMannoseMercaptoethanolMiceModels, ChemicalPentetic AcidPolymersProtein BindingRadiochemistryRatsRats, Sprague-DawleySentinel Lymph Node BiopsyTechnetium CompoundsTechnetium Tc 99m Aggregated AlbuminTechnetium Tc 99m MedronateTemperatureThiocyanatesTime FactorsTin CompoundsTissue Distribution