Ambient light resistant shortwave infrared fluorescence imaging for preclinical tumor delineation via the pH low-insertion peptide conjugated to indocyanine green Journal Article


Authors: Mc Larney, B. E.; Kim, M.; Roberts, S.; Skubal, M.; Hsu, H. T.; Ogirala, A.; Pratt, E. C.; Pillarsetty, N. V. K.; Heller, D. A.; Lewis, J. S.; Grimm, J.
Article Title: Ambient light resistant shortwave infrared fluorescence imaging for preclinical tumor delineation via the pH low-insertion peptide conjugated to indocyanine green
Abstract: 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. COPYRIGHT © 2023 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords: neoplasm; neoplasms; mouse; animal; animals; mice; fluorescence; surgery; tumor; fluorescence imaging; optical imaging; ecosystem; procedures; indocyanine green; preclinical; swir; phlip protein
Journal Title: Journal of Nuclear Medicine
Volume: 64
Issue: 10
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2023-10-01
Start Page: 1647
End Page: 1653
Language: English
DOI: 10.2967/jnumed.123.265686
PUBMED: 37620049
PROVIDER: scopus
PMCID: PMC10586478
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK authors are Benedict Edward Mc Larney and Jan Grimm -- Source: Scopus
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MSK Authors
  1. Jan Grimm
    93 Grimm
  2. Jason S Lewis
    456 Lewis
  3. Daniel Alan Heller
    112 Heller
  4. Anuja   Ogirala
    13 Ogirala
  5. Hsiao Ting Charlene Hsu
    14 Hsu
  6. Edwin C Pratt
    20 Pratt
  7. Sheryl Roberts
    23 Roberts
  8. Magdalena Skubal
    10 Skubal
  9. Mijin Kim
    12 Kim