[¹⁸F]fluoroethyltyrosine-induced Cerenkov Luminescence Improves Image-Guided Surgical Resection of Glioma

Abstract

The extent of surgical resection is significantly correlated with outcome in glioma; however, current intraoperative navigational tools are useful only in a subset of patients. We show here that a new optical intraoperative technique, Cerenkov luminescence imaging (CLI) following intravenous injection of O‑(2-[18F]fluoroethyl)-L-tyrosine (FET), can be used to accurately delineate glioma margins, performing better than the current standard of fluorescence imaging with 5-aminolevulinic acid (5-ALA).Methods: Rats implanted orthotopically with U87, F98 and C6 glioblastoma cells were injected with FET and 5-aminolevulinic acid (5-ALA). Positive and negative tumor regions on histopathology were compared with CL and fluorescence images. The capability of FET CLI and 5-ALA fluorescence imaging to detect tumor was assessed using receptor operator characteristic curves and optimal thresholds (CLIOptROC and 5-ALAOptROC) separating tumor from healthy brain tissue were determined. These thresholds were used to guide prospective tumor resections, where the presence of tumor cells in the resected material and in the remaining brain were assessed by Ki-67 staining.Results: FET CLI signal was correlated with signal in preoperative PET images (y = 1.06x - 0.01; p < 0.0001) and with expression of the amino acid transporter SLC7A5 (LAT1). FET CLI (AUC = 97%) discriminated between glioblastoma and normal brain in human and rat orthografts more accurately than 5-ALA fluorescence (AUC = 91%), with a sensitivity >92% and specificity >91%, and resulted in a more complete tumor resection.Conclusion: FET CLI can be used to accurately delineate glioblastoma tumor margins, performing better than the current standard of fluorescence imaging following 5-ALA administration, and is therefore a promising technique for clinical translation.

Imaging temozolomide-induced changes in the myeloid glioma microenvironment

“…Additionally, MRI results are negatively influenced by therapeutic effects, such as pseudoresponse occurring during VEGFR therapy 12 . Molecular imaging can complement the use of MRI 13 and be of help to better identify specific non-responsive tumor areas. For this reason, combinatorial approaches using non-invasive imaging, such as amino acid PET, with MRI have become the guideline-recommended standard to diagnosis and classification of gliomas 14 .…”

A novel in vivo Cerenkov luminescence image‐guided surgery on primary and metastatic colorectal cancer

“…The feasibility of CL image‐guided surgery has been proved in previous studies . Endoscopic CLI or ex vivo CLI was preferred for intraoperative application because the CLI signals were easily being disturbed by the ambient light . Aiming to satisfy the demand for open CRC surgery, a novel intraoperative in vivo CLI system was developed in this study to complement the surgeon observation.…”

“…CLI has been proved as a promising imaging modality for numerous biomedical applications. The feasibility of CL image‐guided surgery has been proved in previous studies . Endoscopic CLI or ex vivo CLI was preferred for intraoperative application because the CLI signals were easily being disturbed by the ambient light .…”

“…Integrated with clinical laparoscopes, CL image‐guided surgery showed superior performance in liver cancer treatment . Visualizing the tumor margin by the intraoperative CLI, precise resection of glioma was also achievable . These excellent preclinical results encouraged further exploration and clinical application of CL image‐guided surgery.…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…Cheng's team reported an α v β 3 integrin-targeted PET/NIR II nanoprobe ( 68 Ga-SCH2) for tumor delineation and targeting IGS. [236][237][238][239][240][241][242][243] compared with FGS using ICG, in subcutaneous breast cancer 4T1 tumor, orthotopic, and orthotopic-ectopic hepatocellular carcinoma tumor models. [235] CL imaging (CLI) has been successfully used for LN mapping and IGS in animal models.…”