Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging

Jeong, Jae Min; Hong, Mee Kyung; Kim, Young Joo; Lee, Jaetae; Kang, Joo Hyun; Lee, Dong Hoon; Chung, June‐Key; Lee, Myung Chul

doi:10.1097/00006231-200412000-00010

Cited by 52 publications

(32 citation statements)

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“…RGD derivatives have been used to investigate a v b 3 integrin expression in vascular and tumor angiogenesis by biologic and clinical researchers (24)(25)(26)(27)(28)(29). In addition, a mannose and stearylamine conjugate (Man-C 18 ) was synthesized to target the mannose receptor of Kupffer cells (30)(31)(32)(33), and a lactose and stearylamine conjugate (Lac-C 18 ) was synthesized to target the asialoglycoprotein receptor in the liver (32,34,35). For radiolabeling with 68 Ga, we conjugated the bifunctional chelating agent SCN-Bz-NOTA to stearylamine (NOTA-C 18 ).…”

Section: Discussionmentioning

confidence: 99%

Nanoparticles Modified by Encapsulation of Ligands with a Long Alkyl Chain to Affect Multispecific and Multimodal Imaging

et al. 2012

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The attachment of specific ligands to the surfaces of nanoparticles is important for medical and biologic imaging. However, covalent modification of nanoparticles has inherent problems in reproducibility because of many factors such as temperature, pH, concentration, and reaction time. Thus, we developed a method for modifying nanoparticles by encapsulation with specific ligand-conjugated amphiphiles. Methods: We synthesized special amphiphiles with a hydrophilic head and a long single-alkyl chain, such as arginine-glycine-aspartic acid-C 18 , mannose-C 18 , lactose-C 18 , and 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-C 18 . And then we produced stable quantum dots (QDs) encapsulated with polysorbate 60 (a branched polyethylene glycol head with a C 18 tail) and the synthesized special amphiphiles. The prepared encapsulated QDs were subject to in vitro and in vivo animal biodistribution studies and small-animal PET studies to confirm their specific binding. Results: The encapsulated QDs could specifically bind to target cells in vitro and in vivo and could be labeled with 68 Ga (a positron emitter) easily and with high efficiency. Conclusion: The nanoparticles encapsulated with special amphiphiles could provide a straightforward and novel imaging solution with multimodality and multispecificity.

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Section: Discussionmentioning

confidence: 99%

Nanoparticles Modified by Encapsulation of Ligands with a Long Alkyl Chain to Affect Multispecific and Multimodal Imaging

et al. 2012

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“…On the other hand, 99m Tc-neomannosyl human serum albumin (MSA) was developed for lymphoscintigraphy or imaging sentinel lymph nodes (Takagi et al, 2004;Jeong et al, 2004b). The terminal mannose residues of MSA bind to the mannose receptors of lymph nodes after subcutaneous or intradermal injection (Takagi et al, 2004;Jeong et al, 2004b;Vera et al, 2001aVera et al, , 2001b.…”

Section: Introduction 99mmentioning

confidence: 99%

“…The terminal mannose residues of MSA bind to the mannose receptors of lymph nodes after subcutaneous or intradermal injection (Takagi et al, 2004;Jeong et al, 2004b;Vera et al, 2001aVera et al, , 2001b. It has been reported that mannosylated bovine serum albumin rapidly binds to Kupffer cells and endothelial cells in the liver when injected into rat intravenously due to the presence of mannose receptor (Magnusson and Berg, 1989;Ogawara et al, 1999).…”

Section: Introduction 99mmentioning

confidence: 99%

Differential receptor targeting of liver cells using 99mTc-neoglycosylated human serum albumins

et al. 2008

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Neolactosyl human serum albumin (LSA) targets asialoglycoprotein receptor and shows high liver uptake due to accumulation in hepatocytes. Although neomannosyl human serum albumin (MSA) also shows high liver uptake, it has been reported to be taken up by Kupffer cells and endothelial cells. We compared the biological properties of LSA and MSA. 99mTc-LSA and 99mTc-MSA biodistribution in mice were investigated after intravenous injection. In vivo localization of rhodaminisothiocyanate (RITC)-LSA and fluoresceineisothiocyanate (FITC)-MSA were investigated in mouse liver. Excretion routes of 99mTc-LSA and 99mTc-MSA metabolites were examined. Both 99mTc-LSA and 99mTc-MSA showed high liver uptakes. RITC-LSA was taken up by hepatocytes whereas FITC-MSA was taken up by Kupffer cells and endothelial cells. 99mTc-MSA showed higher spleen and kidney uptakes than 99mTc-LSA. 99mTc-LSA metabolites excreted in urine and feces accounted for 44.4 and 50.0% of 99mTc-LSA injected, respectively, while 99mTc-MSA metabolites accounted for 51.5 and 10.3%, respectively. In conclusion, LSA is specifically taken up by hepatcytes while MSA by Kupffer cells and endothelial cells. After taken up by the liver, LSA is metabolized by the hepatocytes and then excreted through both the hepatobiliary tract and kidney, whereas MSA is metabolized by Kupffer cells and endoghelial cells and then excreted mainly through the kidney.

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“…Methods previously described in the literature were used to synthesize MSA from human serum albumin (13,19), RITC-MSA (15), and NOTA-MSA for 68 Ga labeling (17). The labeling efficiency and radiochemical purity determined by instant thin-layer chromatography silica gel were always greater than 98%.…”

Section: Methodsmentioning

confidence: 99%

“…Neomannosylated human serum albumin (MSA) was developed initially for lymphoscintigraphy and imaging of the sentinel lymph nodes (12,13) based on the binding of the terminal mannose residues of MSA to the specific MRs of the lymph nodes. When intravenously injected into rats, mannosylated bovine serum albumin rapidly binds to the Kupffer and endothelial cells in the liver because of the presence of MRs on these cells (14,15).…”

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confidence: 99%

Novel PET Imaging of Atherosclerosis with ⁶⁸Ga-Labeled NOTA-Neomannosylated Human Serum Albumin

Kim

Seo

et al. 2016

J Nucl Med

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Activated macrophages take up 18 F-FDG via glucose transporters, so this compound is useful for atherosclerosis imaging by PET. However, 18 F-FDG application is limited for imaging of the heart and brain, in which glucose uptake is high, and in patients with aberrant glucose metabolism. The aims of this study were to confirm that mannosylated human serum albumin (MSA) specifically binds to the mannose receptor (MR) on macrophages and to test the feasibility of 68 Ga-labeled NOTA-MSA for PET imaging of atherosclerotic plaques. Methods: The peritoneal macrophages of C57/B6 mice were collected, incubated with rhodamine B isothiocyanate-MSA (10 μg/mL), and evaluated by confocal microscopy and flow cytometry. The same evaluations were performed after preincubation of the macrophages with anti-CD206 MR blocking antibodies. NOTA-MSA was synthesized by conjugating 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid to MSA, followed by labeling with 68 Ga. Rabbits with atherosclerotic aorta induced by a 3-mo cholesterol diet and chronic inflammation underwent consecutive PET/CT with 18 F-FDG and 68 Ga-NOTA-MSA at 2-d intervals. Results: The binding of MSA to MR and its dose-dependent reduction by preincubation with anti-CD206 MR blocking antibody were confirmed. Rhodamine B isothiocyanate and fluorescein isothiocyanate fluorescence colocalized at the atherosclerotic plaque. The 68 Ga-NOTA-MSA SUVs of the atherosclerotic aorta were significantly higher than those of the healthy arteries and inferior vena cava and were comparable to those obtained with 18 F-FDG. Conclusion: These findings suggest that MR-specific 68 Ga-NOTA-MSA is effective for detecting atherosclerosis in the aorta and is a promising radiopharmaceutical for imaging atherosclerosis because of the presence of M2 macrophages in atherosclerotic plaques.

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Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging

Abstract: 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.

Cited by 52 publications

References 15 publications

Nanoparticles Modified by Encapsulation of Ligands with a Long Alkyl Chain to Affect Multispecific and Multimodal Imaging

Nanoparticles Modified by Encapsulation of Ligands with a Long Alkyl Chain to Affect Multispecific and Multimodal Imaging

Differential receptor targeting of liver cells using 99mTc-neoglycosylated human serum albumins

Novel PET Imaging of Atherosclerosis with ⁶⁸Ga-Labeled NOTA-Neomannosylated Human Serum Albumin

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Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging

Abstract: 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.

Cited by 52 publications

References 15 publications

Nanoparticles Modified by Encapsulation of Ligands with a Long Alkyl Chain to Affect Multispecific and Multimodal Imaging

Nanoparticles Modified by Encapsulation of Ligands with a Long Alkyl Chain to Affect Multispecific and Multimodal Imaging

Differential receptor targeting of liver cells using 99mTc-neoglycosylated human serum albumins

Novel PET Imaging of Atherosclerosis with 68Ga-Labeled NOTA-Neomannosylated Human Serum Albumin

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Novel PET Imaging of Atherosclerosis with ⁶⁸Ga-Labeled NOTA-Neomannosylated Human Serum Albumin