Photoacoustic and Fluorescence Imaging of Cutaneous Squamous Cell Carcinoma in Living Subjects Using a Probe Targeting Integrin αvβ6

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. Today, cSCC is diagnosed by visual inspection followed by invasive skin biopsy. There is a need to develop non-invasive diagnostic tools to achieve early and accurate detection. Photoacoustic imaging (PAI) possesses high ultrasonic resolution and strong optical contrast at new depths (<1–5 cm). Together with exogenous contrast agents, PAI has found promising use in various tumors in living subjects. The expression of integrin αvβ6 is significantly up-regulated in cSCC. We fabricated an anti-integrin αvβ6 antibody and labeled it with indocyanine green (ICG) to form an ICG-αvβ6 antibody. The results showed that the ICG-αvβ6 antibody probe could be used to detect cSCC with high specificity (3-fold over the control by PAI) and deep penetration (approximately 1 cm) by PAI. This suggests that the ICG-αvβ6 antibody is a promising probe targeting the integrin αvβ6 for detection of cSCC tumors by PAI and fluorescence imaging. It may find clinical application in the early diagnosis of cSCC as well as in intraoperative navigation.

<p>NIR fluorescence-guided tumor surgery: new strategies for the use of indocyanine green</p>

“…This is related to a unique property of ICG: it loses fluorescence when bound to the antibody, but regains it once it is chemically separated from the antibody, which occurs after internalization and degradation of the conjugate 85Table 5ICG-antibodies complexationLigand/TargetTargetType of ICGTumor natureCell typesIn vivo modelAdministration routesReferencesPanitumumabEGFR/HER-1ICG- sulfo-OSuColorectal carcinomaLS-174T cellsFemale athymic nude miceIntravenous injection(88)PanitumumabEGFR/HER-1ICG-Sulfo-OSuBreast cancerMDA-MB-468Female athymic nude miceTail vein injection(86)PanitumumabEGFR/HER-1Amine-reactive PEGylated ICGSquamous carcinomaA431 cells––(87)Daclizumab, trastuzumab, panitumumabIL2R α-chain, HER-2, EGFR/HER-1ICG-Sulfo-OSu–ATAC4, A431, MDA-MB468, NIH3T3 cellsMiceIntravenous injection(33)J591PSMAICG-Sulfo-OSuProstate cancerPC3 cellsAthymic nude miceTail vein injection(85)Anti- α v β 6 antibodyIntegrin α v β 6 ICG-NHSSquamous carcinomaA431 cellsFemale nude miceTail vein injection(93) Abbreviations: ICG- sulfo-OSu, ICG-N-hydroxysulfosuccinimide ester; PSMA, anti-prostate specific membrane antigen. …”

“…Finally, Zhang et al93 fabricated an anti-integrin αvβ6 antibody and labeled it with ICG to form an ICG-αvβ6 antibody. The expression of αvβ6 integrin is significantly upregulated in cutaneous squamous cell carcinoma (cSCC) 94,95.…”

Leveraging Engineering of Indocyanine Green-Encapsulated Polymeric Nanocomposites for Biomedical Applications

“…Strong photoacoustic signals provide conspicuous light absorbance, clear spatial resolution, high conversion efficiency, and a reliable supervision approach under the irradiation of a NIR laser [ 151 , 152 ]. In one case, Zhang et al fabricated ICG-labeled antibody molecules, which efficiently detected the cutaneous squamous cell carcinoma at deeper penetration (<1–5 cm) and high accuracy by PAI and FI as a potential probe [ 153 ]. In another study, Zanganeh et al administered ICG-conjugated nanotubes that significantly improved the observation of an accurate tumor site and confirmed the light absorption of cancer areas at the PAI level, in the meantime, the enhanced, robust system was also confirmed by the captured fluorescent images [ 154 ].…”

Overview of Ultrasound Detection Technologies for Photoacoustic Imaging

“…Due to the widely used intermediate penetration depth achieved by IR light, higher sensitivity of IR devices, and the fast growing advancement of IR optical components, most of photoacoustic systems are implemented in this regime. Infrared photoacoustic technology has been successfully used in both preclinical (to study small animal brain [19][20][21][22], eye [23][24][25][26], and skin [27][28][29]) and clinical (to detect breast cancer [30][31][32], cervical cancer [33,34], skin melanoma [35,36], and brain tumor [37,38]) applications.…”