Paired-Agent Fluorescence Molecular Imaging of Sentinel Lymph Nodes Using Indocyanine Green as a Control Agent for Antibody-Based Targeted Agents.

Chengyue Li,Nathan Mcmahon,Omar Alhaj Ibrahim,Xiaochun Xu,Husain A Sattar,Kenneth M Tichauer

doi:10.1155/2019/7561862

Abstract

Purpose Paired-agent molecular imaging methods, which employ coadministration of an untargeted, “control” imaging agent with a targeted agent to correct for nonspecific uptake, have been demonstrated to detect 200 cancer cells in a mouse model of metastatic breast cancer. This study demonstrates that indocyanine green (ICG), which is approved for human use, is an ideal control agent for future paired-agent studies to facilitate eventual clinical translation. Methods The kinetics of ICG were compared with a known ideal control imaging agent, IRDye-700DX-labeled antibody in both healthy and metastatic rat popliteal lymph nodes after coadministration, intradermally in the footpad. Results The kinetics of ICG and antibody-based imaging agent in tumor-free rat lymph nodes demonstrated a strong correlation with each other (r = 0.98, p < 0.001) with a measured binding potential of −0.102 ± 0.03 at 20 min postagent injection, while the kinetics of ICG and targeted imaging agent shows significant separation in the metastatic lymph nodes. Conclusion This study indicated a potential for microscopic sensitivity to cancer spread in sentinel lymph nodes using ICG as a control agent for antibody-based molecular imaging assays.

Highlights

Identification of cancer spread to tumor draining lymph nodes through lymph node dissection and histology assessment is an established staging procedure in the management of many cancers, predominantly breast carcinoma and melanoma [1]. e clinical protocol in breast carcinoma varies slightly from institute to institute but typically involves (1) node localization through lymphoscintigraphy (gamma probe detection of 99mTc-sulfur colloid spread from peritumoral or subareolar injection site to tumor-draining lymph node(s) [2]) and/or visualized blue dye mapping [3], (2) surgical dissection of the lymph node, and (3) histological examination by a trained pathologist who manually scans select slices of the H&E stained lymph node for cancer cell presence [4]
As a first in vivo step in demonstrating the feasibility of using indocyanine green (ICG) as a control imaging agent, the optimized combined solution of albumin, ICG, and fluorescent antibody was injected into the footpads of nontumor bearing, control rats (n 5 with IRDye 700DX-immunoglobulin G (IgG) + ICG + albumin; n 1 with IRDye 700DX-cetuximab + ICG + albumin). e goal was to demonstrate the similarity in the lymph node kinetics of ICG and two types of fluorescent antibodies
The removal of lymph nodes, even sentinel nodes, can impact the quality of life of patients [6] as the surgery carries a significant risk of morbidity, and with the majority of lymph nodes identified as cancer negative [7], overtreatment is a serious concern. ese limitations of standard lymph node biopsy have led to a demand for the development of an approach to estimate tumor burden lymph nodes noninvasively [41]

Summary

Introduction

Histology analysis of lymph nodes can be timeconsuming and delay subsequent procedures; and pressure to achieve earlier detection of more aggressive breast cancer has led to an increasing number of dissections on tumor-free nodes: estimated to be higher than 70% [7]. Motivated by these drawbacks, considerable efforts have been made to develop imaging techniques that can assess the metastatic status of sentinel lymph nodes noninvasively [8].

Methods

Results

Conclusion