Hybrid lymph node imaging using Cu-64-labeled mannose-conjugated human serum albumin with and without indocyanine green

作者：Kang Choong Mo; An Gwang Il; Choe Yearn Seong^*

来源：Nuclear Medicine Communications, 2015, 36(10): 1026-1034.

DOI：10.1097/MNM.0000000000000353

• Cerenkov luminescence
• Cu-64-labeled mannose-conjugated human serum albumin
• hybrid imaging
• indocyanine green
• near-infrared fluorescence
• PET
• sentinel lymph nodes

ObjectiveHuman serum albumin (HSA), which has 58 Lys residues, one Cys residue, and indocyanine green (ICG) adsorption sites, can be used as a multifunctional platform for the development of hybrid imaging probes. In this study, we prepared Cu-64-labeled mannose-conjugated HSA with and without ICG ([Cu-64]1-ICG and [Cu-64]1, respectively) and compared hybrid PET/near-infrared fluorescence (NIRF) imaging with positron emission tomography (PET)/Cerenkov luminescence (CL) imaging of lymph nodes (LNs).Materials and methods1,4,7,10-Tetraazacyclododecane-N,N,N,N-tetraacetic acid (DOTA)/mannose-conjugated HSA (1) was synthesized by conjugating mannose molecules to Lys residues and a DOTA molecule to a Cys residue of HSA. Compound 1 was then labeled with Cu-64 ([Cu-64]1), and the resulting [Cu-64]1 was adsorbed with ICG ([Cu-64]1-ICG). PET/NIRF or PET/CL imaging and subsequent biodistribution studies were performed in ICR mice after injection of the probes into the foot pads.ResultsThe numbers of mannose and DOTA molecules conjugated to HSA were 7.170.49 and 0.95 +/- 0.18, respectively. The site-specific conjugation of one DOTA molecule to HSA was sufficient for Cu-64-labeling with high efficiency (96.0 +/- 1.1%). PET/NIRF and PET/CL imaging and subsequent biodistribution studies demonstrated that the probes were avidly taken up by the popliteal LNs (PO), with a slightly higher uptake ratio of the PO to the lumbar LNs by [Cu-64]1.ConclusionIn-vivo studies suggest that [Cu-64]1 has more specific and selective binding to mannose receptors in the PO than [Cu-64]1-ICG.

• 出版日期2015-10