RT Journal Article
SR Electronic
T1 Ambient Light Resistant Shortwave Infrared Fluorescence Imaging for Preclinical Tumor Delineation via the pH Low-Insertion Peptide Conjugated to Indocyanine Green
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1647
OP 1653
DO 10.2967/jnumed.123.265686
VO 64
IS 10
A1 Mc Larney, Benedict Edward
A1 Kim, Mijin
A1 Roberts, Sheryl
A1 Skubal, Magdalena
A1 Hsu, Hsiao-Ting
A1 Ogirala, Anuja
A1 Pratt, Edwin C.
A1 Pillarsetty, Naga Vara Kishore
A1 Heller, Daniel A.
A1 Lewis, Jason S.
A1 Grimm, Jan
YR 2023
UL http://jnm.snmjournals.org/content/64/10/1647.abstract
AB Shortwave infrared (900–1,700 nm) fluorescence imaging (SWIRFI) has shown significant advantages over visible (400–650 nm) and near-infrared (700–900 nm) fluorescence imaging (reduced autofluorescence, improved contrast, tissue resolution, and depth sensitivity). However, there is a major lag in the clinical translation of preclinical SWIRFI systems and targeted SWIRFI probes. Methods: We preclinically show that the pH low-insertion peptide conjugated to indocyanine green (pHLIP ICG), currently in clinical trials, is an excellent candidate for cancer-targeted SWIRFI. Results: pHLIP ICG SWIRFI achieved picomolar sensitivity (0.4 nM) with binary and unambiguous tumor screening and resection up to 96 h after injection in an orthotopic breast cancer mouse model. SWIRFI tumor screening and resection had ambient light resistance (possible without gating or filtering) with outstanding signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values at exposures from 10 to 0.1 ms. These SNR and CNR values were also found for the extended emission of pHLIP ICG in vivo (>1,100 nm, 300 ms). Conclusion: SWIRFI sensitivity and ambient light resistance enabled continued tracer clearance tracking with unparalleled SNR and CNR values at video rates for tumor delineation (achieving a tumor-to-muscle ratio above 20). In total, we provide a direct precedent for the democratic translation of an ambient light resistant SWIRFI and pHLIP ICG ecosystem, which can instantly improve tumor resection.