A tri-modal molecular imaging agent for sentinel lymph node mapping

Zhengtao Qin; Carl K Hoh; David J Hall; David R Vera

doi:10.1016/j.nucmedbio.2015.07.011

A tri-modal molecular imaging agent for sentinel lymph node mapping

Nucl Med Biol. 2015 Dec;42(12):917-22. doi: 10.1016/j.nucmedbio.2015.07.011. Epub 2015 Jul 31.

Authors

Zhengtao Qin¹, Carl K Hoh², David J Hall², David R Vera³

Affiliations

¹ Department of Chemistry, University of California, San Diego, La Jolla, California; Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California; UCSD In Vivo Cancer and Molecular Imaging Center, University of California, San Diego, La Jolla, California.
² Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California; UCSD In Vivo Cancer and Molecular Imaging Center, University of California, San Diego, La Jolla, California.
³ Moores UCSD Cancer Center, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California; UCSD In Vivo Cancer and Molecular Imaging Center, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California. Electronic address: dvera@ucsd.edu.

PMID: 26320812
DOI: 10.1016/j.nucmedbio.2015.07.011

Abstract

Introduction: We report an "instant kit" method to radiolabel fluorescent-tilmanocept with (68)Ga and (99m)Tc for tri-modal molecular imaging of sentinel lymph nodes (SLNs).

Methods: Solutions of sodium acetate, (68)GaCl(3) and Na(99m)TcO(4) were added successively to a "kit vial" containing lyophilized 800CW-tilmanocept, SnCl(2), trehalose and ascorbic acid. After a 30-min incubation, the pH was neutralized with PBS. No purification was required. Radiochemical and fluorescence purity was measured by HPLC and ITLC techniques. In vitro stability was measured by standing gel chromatography (SGC) and ITLC by a 100-fold dilution 0.25 h after radiolabeling. In vivo stability was measured by SGC and ITLC after an 11h incubation in human plasma. A dose (0.1 nmol, ~1MBq (68)Ga, ~25M Bq (99m)Tc) was injected to the footpad of 4 mice. Popliteal SLNs were imaged by PET and fluorescence imaging systems at 0.5, 24, 48, 72 h, then excised and assayed for (99m)Tc.

Results: Radiochemical and fluorescent purity exceeded 98%. The in vitro stability assay demonstrated high irreversibility of both radiolabels and the fluorescent label, and in vivo stability assay demonstrated high stability of the technetium and fluorescent labels to plasma metabolism. Popliteal SLNs were identified by PET and fluorescence imaging within 0.5 h of injection. SLN fluorescence intensity remained constant for 72 h, when ~1% of the injected dose resided in the SLN.

Conclusions: Fluorescent-labeled tilmanocept can be radiolabeled with (68)Ga and (99m)Tc by the sequential addition of each generator eluate to a lyophilized kit. The resulting tri-modal agent provides: PET images for pre-operative SLN mapping, fluorescence imaging up to 72 hours after injection, and quantitative radiometric measurement of SLN accumulation after excision.

Keywords: Fluorescence imaging; IRDye800CW-tilmanocept; Multimodality imaging; PET imaging; Sentinel lymph node; Tilmanocept.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Female
Gallium Radioisotopes / pharmacokinetics*
Humans
Lymph Nodes / diagnostic imaging*
Lymph Nodes / surgery
Mice
Molecular Imaging / methods*
Organotechnetium Compounds / pharmacokinetics*
Radionuclide Imaging
Radiopharmaceuticals / pharmacokinetics*
Sentinel Lymph Node Biopsy*

Substances

Gallium Radioisotopes
Organotechnetium Compounds
Radiopharmaceuticals

Grants and funding

P50 CA128346/CA/NCI NIH HHS/United States