Detection of Shortwave-Infrared Cerenkov Luminescence from Medical Isotopes

Larney, Ben Mc; Zhang, Qize; Pratt, Edwin C.; Skubal, Magdalena; Isaac, Elizabeth; Hsu, Hsiao-Ting; Ogirala, Anuja; Grimm, Jan

doi:10.2967/jnumed.122.264079

Cited by 13 publications

(14 citation statements)

References 61 publications

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“…Since light is generated even in the depth of tissue this approach is suitable for PDT [ 39 ]. Additionally, a new approach compared CL imaging in the visible light range with short-waved infrared CL imaging, showing several advantages regarding the penetration depth and scattering effects [ 40 ]. Therefore, different explanations need to be found for the effects described in the literature.…”

Section: Discussionmentioning

confidence: 99%

Psoralen as a Photosensitizers for Photodynamic Therapy by Means of In Vitro Cherenkov Light

Hübinger

Runge

Rosenberg

et al. 2022

IJMS

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Possible enhancements of DNA damage with light of different wavelengths and ionizing radiation (Rhenium-188—a high energy beta emitter (Re-188)) on plasmid DNA and FaDu cells via psoralen were investigated. The biophysical experimental setup could also be used to investigate additional DNA damage due to photodynamic effects, resulting from Cherenkov light. Conformational changes of plasmid DNA due to DNA damage were detected and quantified by gel electrophoresis and fluorescent staining. The clonogene survival of the FaDu cells was analyzed with colony formation assays. Dimethyl sulfoxide was chosen as a chemical modulator, and Re-188 was used to evaluate the radiotoxicity and light (UVC: λ = 254 nm and UVA: λ = 366 nm) to determine the phototoxicity. Psoralen did not show chemotoxic effects on the plasmid DNA or FaDu cells. After additional treatment with light (only 366 nm—not seen with 254 nm), a concentration-dependent increase in single strand breaks (SSBs) was visible, resulting in a decrease in the survival fraction due to the photochemical activation of psoralen. Whilst UVC light was phototoxic, UVA light did not conclude in DNA strand breaks. Re-188 showed typical radiotoxic effects with SSBs, double strand breaks, and an overall reduced cell survival for both the plasmid DNA and FaDu cells. While psoralen and UVA light showed an increased toxicity on plasmid DNA and human cancer cells, Re-188, in combination with psoralen, did not provoke additional DNA damage via Cherenkov light.

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Section: Discussionmentioning

confidence: 99%

Psoralen as a Photosensitizers for Photodynamic Therapy by Means of In Vitro Cherenkov Light

Hübinger

Runge

Rosenberg

et al. 2022

IJMS

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“…Shor twave infrared (SWIR, 900-1,700 nm, or the second nearinfrared [NIR] window) fluorescence imaging (SWIRFI) is providing novel insights for preclinical and clinical biophotonic imaging (1)(2)(3)(4)(5). In the SWIR spectrum, tissue scattering, absorption, and autofluorescence are negligible, permitting higher contrast, deeper penetration, and improved resolution (6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Ambient Light Resistant Shortwave Infrared Fluorescence Imaging for Preclinical Tumor Delineation via the pH Low-Insertion Peptide Conjugated to Indocyanine Green

Mc Larney,

Kim,

Roberts

et al. 2023

J Nucl Med

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Shortwave infrared (900-1,700 nm) fluorescence imaging (SWIRFI) has shown significant advantages over visible (400-650 nm) and nearinfrared (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.

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“…1 A. 6,40,41 We found that CJ215 underwent a spectral red shifting similar to that seen with ICG when dissolved in fetal bovine serum (FBS), Fig. 1 A.…”

Section: Resultsmentioning

confidence: 73%

A pan-cancer agent for screening, resection and wound monitoring via NIR and SWIR imaging

Larney,

Sonay,

Apfelbaum

et al. 2024

Preprint

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Fluorescence guided surgery (FGS) facilitates real time tumor delineation and is being rapidly established clinically. FGS efficacy is tied to the utilized dye and provided tumor contrast over healthy tissue. Apoptosis, a cancer hallmark, is a desirable target for tumor delineation. Here, we preclinically in vitro and in vivo, validate an apoptosis sensitive commercial carbocyanine dye (CJ215), with absorption and emission spectra suitable for near infrared (NIR, 650-900nm) and shortwave infrared (SWIR, 900-1700nm) fluorescence imaging (NIRFI, SWIRFI). High contrast SWIRFI for solid tumor delineation is demonstrated in multiple murine and human models including breast, prostate, colon, fibrosarcoma and intraperitoneal colorectal metastasis. Organ necropsy and imaging highlighted renal clearance of CJ215. SWIRFI and CJ215 delineated all tumors under ambient lighting with a tumor-to-muscle ratio up to 100 and tumor-to-liver ratio up to 18, from 24 to 168 h post intravenous injection with minimal uptake in healthy organs. Additionally, SWIRFI and CJ215 achieved non-contact quantifiable wound monitoring through commercial bandages. CJ215 provides tumor screening, guided resection, and wound healing assessment compatible with existing and emerging clinical solutions.

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Detection of Shortwave-Infrared Cerenkov Luminescence from Medical Isotopes

Cited by 13 publications

References 61 publications

Psoralen as a Photosensitizers for Photodynamic Therapy by Means of In Vitro Cherenkov Light

Psoralen as a Photosensitizers for Photodynamic Therapy by Means of In Vitro Cherenkov Light

Ambient Light Resistant Shortwave Infrared Fluorescence Imaging for Preclinical Tumor Delineation via the pH Low-Insertion Peptide Conjugated to Indocyanine Green

A pan-cancer agent for screening, resection and wound monitoring via NIR and SWIR imaging

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