title: Development of 68Ga-labeled mannosylated human serum albumin (MSA) as a lymph node imaging agent for positron emission tomography.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jae Yeon
authors.initials: JY
authors.lastname: Choi
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Kyunggon
authors.initials: K
authors.lastname: Kim
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Bo Yeun
authors.initials: BY
authors.lastname: Yang
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Lee
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry; D008198:Lymph Nodes / Q000000981:diagnostic imaging*; D008297:Male; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D049268:Positron-Emission Tomography / Q000379:methods*; D011487:Protein Conformation; D012709:Serum Albumin / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D002614:Chelating Agents; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D017879:Isothiocyanates; D012709:Serum Albumin; C082060:2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid; D008358:Mannose