A thiopyrylium salt for PET/NIR‐II tumor imaging and image‐guided surgery

Abstract

All tumor imaging modalities have resolution limits below which deeply situated small metastatic foci may not be identified. Moreover, incomplete lesion excision will affect the outcomes of the patients. Scintigraphy is adept in locating lesions, and second near-infrared window (NIR-II) imaging may allow precise real-time tumor delineation. To achieve complete excision of all lesions, multimodality imaging is a promising method for tumor identification and management. Here, a NIR-II thiopyrylium salt, XB1034, was first synthesized and bound to cetuximab and trans-cyclooctene (TCO) to produce XB1034-cetuximab-TCO. This probe provides excellent sensitivity and high temporal resolution NIR-II imaging in mice bearing tumors developed from human breast cancer cells MDA-MB-231. To enable PET imaging, 68 Ga-NETA-tetrazine is subsequently injected into the mice to undergo a bio-orthogonal reaction with the preinjected XB1034-cetuximab-TCO. PET images achieved in the tumor models using the pretargeting strategy are of much higher quality than those obtained using the direct radiolabeling method. Moreover, real-time NIR-II imaging allows accurate tumor excision and sentinel lymph node mapping. In conclusion, XB1034 is a promising molecular imaging probe for tumor diagnosis and treatment.Abbreviations DCE, dichloroethane; EGFR, epidermal growth factor receptor; H&E, hematoxylin and eosin; HOMOs, highest occupied molecular orbitals; HPLC, high-performance liquid chromatography; ICG, indocyanine green; LP, long pass; LUMOs, lowest unoccupied molecular orbitals; MALDI-TOF MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; MTT, methyl thiazolyl tetrazolium; NETA-Tz, tetrazine-(2,2 0 -((6-amino-1-(4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl)hexan-2-yl)azanediyl)diacetic acid; NIR-II, second near-infrared window;

Hydrophobic insertion-based engineering of tumor cell-derived exosomes for SPECT/NIRF imaging of colon cancer

“…SPECT can be used to image the whole body and offers excellent penetration; however, SPECT imaging is limited by the relatively long acquisition time, short imaging time window, and low spatial resolution. Near-infrared fluorescence (NIRF, 650–1000 nm) imaging offers real-time and high-resolution tissue structure information [ 25 , 26 ], although tissue penetration is limited. Multimodality SPECT and NIRF imaging can provide complementary insight into disease progression and real-time tumor delineation [ 27 ].…”

Dual Probes for Positron Emission Tomography (PET) and Fluorescence Imaging (FI) of Cancer

“…Zhang et al developed a XB1034-cetuximab-TCO conjugate, where XB1034 is a thiopyrylium NIR-II fluorophore and TCO is a reactive trans-cyclooctene ( Figure 12 ) [ 57 ]. Cetuximab is a monoclonal antibody (~150 kDa) that confers selectivity for epidermal growth factor receptor (EGFR), which is often overexpressed in several types of cancers [ 58 , 59 , 60 ].…”

“…NIRF imaging ( A ) and PET images ( B ) in MDA-MB231 xenograft tumors at various time points after 68 Ga-NETA-Tz injection (Reprinted from ref. [ 57 ]. Copyright 2020 FEBS Press and John Wiley & Sons Ltd.)…”

Extracellular Vesicles-based Pre-Targeting Strategy Enables Multi-Modal Imaging of Orthotopic Colon Cancer and Image-Guided Surgery

“…Orthotopic colon cancer models were also prepared with the following protocol. The 5-week BALB/C nude mice were laparotomized to expose the cecum, then HCT116 cells (5 × 6 ) suspended in 50 µL PBS were injected into the serosal layer of the colon. Four weeks after cell injections, the mice were prepared for study.…”

“…Near-infrared uorescence (NIRF, 650-1000 nm) imaging can provide anatomical information and real-time delineation of tumor because of the advantages of high temporal resolution, spatial resolution, super sensitivity and lower background [5][6][7]. Therefore, multi-modal PET/CT and NIRF imaging of colon cancer can be applied to obtain preoperative and intraoperative imaging of tumor.…”