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

Choong Mo Kang1, Gwang Il An, Yearn Seong Choe

  • 1aDepartment of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine bDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan University cMolecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.

Insights

This study developed novel hybrid imaging probes using 64Cu-labeled mannose-conjugated human serum albumin. The probes demonstrated selective uptake in lymph nodes, with one variant showing enhanced specificity for mannose receptors.

Area of Science:

  • Biomedical Imaging
  • Radiochemistry
  • Nanotechnology

Background:

  • Human serum albumin (HSA) serves as a versatile platform for developing hybrid imaging probes due to its abundant lysine residues, single cysteine residue, and indocyanine green (ICG) adsorption capabilities.
  • Developing multifunctional imaging probes is crucial for advanced diagnostic applications.

Purpose of the Study:

  • To synthesize and evaluate 64Cu-labeled mannose-conjugated HSA probes, with and without ICG ([64Cu]1-ICG and [64Cu]1, respectively).
  • To compare hybrid positron emission tomography/near-infrared fluorescence (PET/NIRF) imaging with PET/Cerenkov luminescence (CL) imaging for lymph node (LN) visualization.

Main Methods:

  • Synthesis of 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)/mannose-conjugated HSA (1) via conjugation of mannose to lysine residues and DOTA to a cysteine residue.
  • Radiolabeling of compound 1 with 64Cu to form [64Cu]1, followed by ICG adsorption to create [64Cu]1-ICG.
  • In vivo imaging studies in mice using PET/NIRF and PET/CL modalities after injection into foot pads, complemented by biodistribution analysis.

Main Results:

  • Successful site-specific conjugation of mannose (7.17 ± 0.49) and DOTA (0.95 ± 0.18) molecules to HSA.
  • High efficiency (96.0 ± 1.1%) achieved for 64Cu-labeling using a single DOTA molecule.
  • Probes showed avid uptake in popliteal lymph nodes (PO), with [64Cu]1 exhibiting a slightly higher popliteal to lumbar lymph node uptake ratio compared to [64Cu]1-ICG.

Conclusions:

  • In vivo studies indicate that [64Cu]1 demonstrates more specific and selective binding to mannose receptors in the popliteal lymph nodes than [64Cu]1-ICG.
  • The findings support the potential of [64Cu]1 as a targeted imaging agent for lymph nodes.
Abstract

Related Concept Videos