Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging.
OBJECTIVE
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.
Jeong
Jae Min
JM
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea. jmjng@snu.ac.kr
Hong
Mee Kyung
MK
Kim
Young Joo
YJ
Lee
Jaetae
J
Kang
Joo Hyun
JH
Lee
Dong Soo
DS
Chung
June-Key
JK
Lee
Myung Chul
MC
D000818:Animals; D000965:Antimony / Q000737:chemistry; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry; D008198:Lymph Nodes / Q000473:pathology*; D008239:Lysine / Q000737:chemistry; D008297:Male; D008358:Mannose / Q000737:chemistry; D008623:Mercaptoethanol / Q000494:pharmacology; D051379:Mice; D008956:Models, Chemical; D004369:Pentetic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D011854:Radiochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D021701:Sentinel Lymph Node Biopsy / Q000379:methods; D017556:Technetium Compounds / Q000737:chemistry; D013668:Technetium Tc 99m Aggregated Albumin / Q000737:chemistry* / Q000378:metabolism*; D013669:Technetium Tc 99m Medronate / Q000494:pharmacology; D013696:Temperature; D013861:Thiocyanates; D013997:Time Factors; D017971:Tin Compounds / Q000737:chemistry; D014018:Tissue Distribution
D017879:Isothiocyanates; D011108:Polymers; D017556:Technetium Compounds; D013668:Technetium Tc 99m Aggregated Albumin; D013861:Thiocyanates; D017971:Tin Compounds; C019096:technetium Tc 99m antimony sulfide; C033493:technetium Tc 99m tin colloid; C005441:phenylisothiocyanate; D008623:Mercaptoethanol; D004369:Pentetic Acid; D000965:Antimony; D008239:Lysine; D008358:Mannose; D013669:Technetium Tc 99m Medronate