scholarly journals Near Infrared Fluorescence Imaging of Intraperitoneal Ovarian Tumors in Mice Using Erythrocyte-Derived Optical Nanoparticles and Spatially-Modulated Illumination

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2544
Author(s):  
Joshua M. Burns ◽  
Elise Shafer ◽  
Raviraj Vankayala ◽  
Vikas Kundra ◽  
Bahman Anvari
Keyword(s):  
Fluorescence Imaging ◽  
Cytoreductive Surgery ◽  
Animal Studies ◽  
Near Infrared ◽  
Gynecological Cancer ◽  
Ovarian Tumors ◽  
Structured Illumination ◽  
Spatial Frequencies ◽  
Imaging Probes ◽  
Intraoperative Fluorescence Imaging

Ovarian cancer is the deadliest gynecological cancer. Cytoreductive surgery to remove primary and intraperitoneal tumor deposits remains as the standard therapeutic approach. However, lack of an intraoperative image-guided approach to enable the visualization of all tumors can result in incomplete cytoreduction and recurrence. We engineered nano-sized particles derived from erythrocytes that encapsulate the near infrared (NIR) fluorochrome, indocyanine green, as potential imaging probes for tumor visualization during cytoreductive surgery. Herein, we present the first demonstration of the use of these nanoparticles in conjunction with spatially-modulated illumination (SMI), at spatial frequencies in the range of 0–0.5 mm−1, to fluorescently image intraperitoneal ovarian tumors in mice. Results of our animal studies suggest that the nanoparticles accumulated at higher levels within tumors 24 h post-intraperitoneal injection as compared to various other organs. We demonstrate that, under the imaging specifications reported here, use of these nanoparticles in conjunction with SMI enhances the fluorescence image contrast between intraperitoneal tumors and liver, and between intraperitoneal tumors and spleen by nearly 2.1, and 3.0 times, respectively, at the spatial frequency of 0.2 mm−1 as compared to the contrast values at spatially-uniform (non-modulated) illumination. These results suggest that the combination of erythrocyte-derived NIR nanoparticles and structured illumination provides a promising approach for intraoperative fluorescence imaging of ovarian tumor nodules at enhanced contrast.

Rhenium and technetium-complexed silicon rhodamines as near-infrared imaging probes for bimodal SPECT- and optical imaging

2020 ◽  
Vol 49 (22) ◽  
pp. 7294-7298 ◽  
Author(s):  
Thines Kanagasundaram ◽  
Carsten S. Kramer ◽  
Eszter Boros ◽  
Klaus Kopka
Keyword(s):  
Optical Imaging ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Infrared Imaging ◽  
Near Infrared Imaging ◽  
Near Infrared Fluorescence ◽  
Technetium 99M ◽  
Imaging Probes ◽  
Near Infrared Fluorescence Imaging

The first technetium-99m tricarbonyl core labelled fluorescent Si-rhodamine and its rhenium analogue for bimodal SPECT- and near-infrared fluorescence imaging is presented.

Multimodal fluorescence-guided surgery of colorectal peritoneal metastases, a phase I/II clinical trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4119-TPS4119
Author(s):  
Jan-Marie de Gooyer ◽  
Fortuné Elekonawo ◽  
Andre J.A. Bremers ◽  
Otto Boerman ◽  
Mark Rijpkema ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Peritoneal Carcinomatosis ◽  
Real Time ◽  
Fluorescence Imaging ◽  
Cytoreductive Surgery ◽  
Peritoneal Metastases ◽  
Colorectal Origin ◽  
Intraoperative Fluorescence Imaging ◽  
Intraoperative Fluorescence

TPS4119 Background: Successful treatment of patients with colorectal peritoneal carcinomatosis highly depends on complete surgical tumor resection of all tumor. Oncological outcomes can potentially be improved by intraoperative imaging using a tumor-targeting antibody conjugated to a fluorophore and a radiotracer. This enables preoperative radionuclide imaging, real-time intraoperative fluorescence imaging and gamma detection. In this study we investigate the feasibility, accuracy and safety of CEA-targeted preoperative SPECT/CT and intraoperative fluorescence imaging in patients with colorectal PC. Methods: In this phase I/II single arm protein dose escalation study patients with peritoneal metastases of colorectal origin who are scheduled for cytoreductive surgery and HIPEC will receive an intravenous injection of the CEA-targeting tracer 111In-DOTA-labetuzumab-IRDye800CW. The first 15 patients will receive a single dose of 2,10 or 50 mg 6 to 7 days prior to surgery. Four to five days after injection SPECT/CT imaging of the thorax and abdomen is performed to determine intra-abdominal tumor load and detect extra-abdominal metatases. At day 6/7 after injection, standard cytoreductive surgical resection extended with real-time near-infrared fluorescence imaging and radio guidance is performed. After surgery, the peritoneal cavity will be re-examined for residual disease with fluorescence imaging. Resected specimens are analyzed microscopically, immunohistochemically (CEA and H&E) and by gamma counting. Blood samples are drawn for farmacokinetics and safety analysis at 180 minutes, 4 days, 6 days and 3 weeks after tracer injection. In the phase II dose expansion cohort, 14 more patients will receive the optimal dose as determined in the phase I trial. The primary objectives of the trial are to assess the safety, feasibility and accuracy of preoperative SPECT/CT and intraoperative fluorescence imaging after administration of 111In- labetuzumab-IRDye800CW in patients with peritoneal carcinomatosis of colorectal origin who will undergo cytoreductive surgery and HIPEC. The secondary objectives are to assess whether additional malignant lesions can be visualized by fluorescence imaging after cytoreductive surgery, to assess the intensity of fluorescence in malignant and non-malignant tissue, to assess the correlation between localization of the dual-labeled antibody and CEA expression in tumor and healthy tissue and to determine blood concentrations of the dual labelled antibody at several time points in patients. Clinical trial information: NCT03699332 .

scholarly journals Dose-Finding Study of a CEA-Targeting Agent, SGM-101, for Intraoperative Fluorescence Imaging of Colorectal Cancer

2020 ◽  
Author(s):  
Kim S. de Valk ◽  
Marion M. Deken ◽  
Dennis P. Schaap ◽  
Ruben P. Meijer ◽  
Leonora S. Boogerd ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Imaging System ◽  
Dose Finding ◽  
Phase Iii ◽  
Imaging Dose ◽  
Intraoperative Fluorescence Imaging ◽  
Optimal Imaging ◽  
Intraoperative Fluorescence

Abstract Background Carcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC. Methods Patients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose. Results Thirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (p = 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients. Conclusions The optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019.

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