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

Author(s):  
Kim S. de Valk ◽  
Marion M. Deken ◽  
Dennis P. Schaap ◽  
Ruben P. Meijer ◽  
Leonora S. Boogerd ◽  
...  

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.

2009 ◽  
Vol 14 (6) ◽  
pp. 064012 ◽  
Author(s):  
George Themelis ◽  
Jung Sun Yoo ◽  
Kwang-Sup Soh ◽  
Ralf Schulz ◽  
Vasilis Ntziachristos

2017 ◽  
Vol 9 ◽  
pp. 1179299X1772825 ◽  
Author(s):  
Charlotte ES Hoogstins ◽  
Benjamin Weixler ◽  
Leonora SF Boogerd ◽  
Diederik J Hoppener ◽  
Hendrica AJM Prevoo ◽  
...  

Peritoneal metastasis (PM) occurs in about 10% of patients with colorectal cancer (CRC). Fluorescence imaging can enhance contrast between cancerous and benign tissue, enabling the surgeon to clearly visualize PM during cytoreductive surgery. This study assessed the suitability of different biomarkers as potential targets for tumor-targeted imaging of PM of CRC. Tissue samples from primary tumor and PM from patients with CRC were obtained from the pathology archives and immunohistochemical stainings were performed. Overexpression of the epithelial cell adhesion molecule (EpCAM) and carcinoembryonic antigen (CEA) was seen in 100% of PM samples and the expression was strong in >70% of samples. Tyrosine-kinase Met (C-Met) and folate receptor α overexpression was seen in 20% of PM samples. For successful application of tumor-targeted intraoperative fluorescence imaging of PM, biomarkers need to be identified. We demonstrated that both EpCAM and CEA are suitable targets for fluorescence imaging of PM in patients with CRC.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2544
Author(s):  
Joshua M. Burns ◽  
Elise Shafer ◽  
Raviraj Vankayala ◽  
Vikas Kundra ◽  
Bahman Anvari

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.


Biomaterials ◽  
2010 ◽  
Vol 31 (26) ◽  
pp. 6823-6832 ◽  
Author(s):  
Patrick T.K. Chin ◽  
Tessa Buckle ◽  
Arantxa Aguirre de Miguel ◽  
Stefan C.J. Meskers ◽  
René A.J. Janssen ◽  
...  

2006 ◽  
Vol 11 (1) ◽  
pp. 014007 ◽  
Author(s):  
Alec M. De Grand ◽  
Stephen J. Lomnes ◽  
Deborah S. Lee ◽  
Matthew Pietrzykowski ◽  
Shunsuke Ohnishi ◽  
...  

2019 ◽  
Vol 7 (7) ◽  
pp. 2873-2888 ◽  
Author(s):  
Xu Zhang ◽  
Xiaolong Liang ◽  
Xiaotu Ma ◽  
Rui Hou ◽  
Xiaoda Li ◽  
...  

Dye-conjugated cerasome loaded with DOX exhibited high stability and controllable drug release, holding great promise in colorectal cancer photothermal chemotherapy.


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