PT  - JOURNAL ARTICLE
AU  - Mc Larney, Benedict Edward
AU  - Kim, Mijin
AU  - Roberts, Sheryl
AU  - Skubal, Magdalena
AU  - Hsu, Hsiao-Ting
AU  - Ogirala, Anuja
AU  - Pratt, Edwin C.
AU  - Pillarsetty, Naga Vara Kishore
AU  - Heller, Daniel A.
AU  - Lewis, Jason S.
AU  - Grimm, Jan
TI  - Ambient Light Resistant Shortwave Infrared Fluorescence Imaging for Preclinical Tumor Delineation via the pH Low-Insertion Peptide Conjugated to Indocyanine Green
AID  - 10.2967/jnumed.123.265686
DP  - 2023 Oct 01
TA  - Journal of Nuclear Medicine
PG  - 1647--1653
VI  - 64
IP  - 10
4099  - http://jnm.snmjournals.org/content/64/10/1647.short
4100  - http://jnm.snmjournals.org/content/64/10/1647.full
SO  - J Nucl Med2023 Oct 01; 64
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.