Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery.
| Title: | Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery. |
|---|---|
| Authors: | Elekonawo FMK; Department of Radiology, Nuclear Medicine and Anatomy, Radboud Institute for Health Sciences, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; Department of Surgery, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; de Gooyer JM; Department of Radiology, Nuclear Medicine and Anatomy, Radboud Institute for Health Sciences, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; Department of Surgery, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; Bos DL; Department of Radiology, Nuclear Medicine and Anatomy, Radboud Institute for Health Sciences, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; Goldenberg DM; Center for Molecular Medicine and Immunology, Mendham, NJ 07945, USA.; Boerman OC; Department of Surgery, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; Brosens LAA; Department of Pathology, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; Bremers AJA; Department of Surgery, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; de Wilt JHW; Department of Surgery, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; Rijpkema M; Department of Radiology, Nuclear Medicine and Anatomy, Radboud Institute for Health Sciences, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands. |
| Source: | Cancers [Cancers (Basel)] 2020 Apr 17; Vol. 12 (4). Date of Electronic Publication: 2020 Apr 17. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI |
| Abstract: | Image-guided surgery can aid in achieving complete tumor resection. The development and assessment of tumor-targeted imaging probes for near-infrared fluorescence image-guided surgery relies mainly on preclinical models, but the translation to clinical use remains challenging. In the current study, we introduce and evaluate the application of a dual-labelled tumor-targeting antibody for ex vivo incubation of freshly resected human tumor specimens and assessed the tumor-to-adjacent tissue ratio of the detectable signals. Immediately after surgical resection, peritoneal tumors of colorectal origin were placed in cold medium. Subsequently, tumors were incubated with 111In-DOTA-hMN-14-IRDye800CW, an anti-carcinoembryonic antigen (CEA) antibody with a fluorescent and radioactive label. Tumors were then washed, fixed, and analyzed for the presence and location of tumor cells, CEA expression, fluorescence, and radioactivity. Twenty-six of 29 tumor samples obtained from 10 patients contained malignant cells. Overall, fluorescence intensity was higher in tumor areas compared to adjacent non-tumor tissue parts (p < 0.001). The average fluorescence tumor-to-background ratio was 11.8 ± 9.1:1. A similar ratio was found in the autoradiographic analyses. Incubation with a non-specific control antibody confirmed that tumor targeting of our tracer was CEA-specific. Our results demonstrate the feasibility of this tracer for multimodal image-guided surgery. Furthermore, this ex vivo incubation method may help to bridge the gap between preclinical research and clinical application of new agents for radioactive, near infrared fluorescence or multimodal imaging studies. |
| References: | J Am Coll Surg. 2019 Dec;229(6):560-567.e1. (PMID: 31568855); Ann Thorac Surg. 2017 May;103(5):1557-1565. (PMID: 28366464); Clin Cancer Res. 2016 Sep 15;22(18):4634-42. (PMID: 27103404); Theranostics. 2018 Apr 3;8(9):2508-2520. (PMID: 29721096); Theranostics. 2018 Mar 8;8(8):2161-2170. (PMID: 29721070); Lancet Oncol. 2019 Jul;20(7):e354-e367. (PMID: 31267970); Lancet Gastroenterol Hepatol. 2018 Mar;3(3):181-191. (PMID: 29361435); Biochem Biophys Res Commun. 2005 Jul 22;333(1):223-9. (PMID: 15958210); Gynecol Oncol. 2014 Sep;134(3):462-7. (PMID: 25026637); Ann Surg Oncol. 2016 Nov;23(12):3811-3821. (PMID: 27527715); Colorectal Dis. 2012 Dec;14(12):1457-66. (PMID: 22356246); Lancet Gastroenterol Hepatol. 2016 Dec;1(4):283-290. (PMID: 28404198); JAMA Surg. 2015 Sep;150(9):890-8. (PMID: 26132363); Mol Pharm. 2017 Oct 2;14(10):3457-3463. (PMID: 28826214); Cancer Res. 1996 Apr 15;56(8):1805-16. (PMID: 8620497); Indian J Urol. 2014 Oct;30(4):423-8. (PMID: 25378825); Anticancer Drugs. 2010 Oct;21(9):861-7. (PMID: 20700044); Cancer Med. 2016 Jul;5(7):1526-34. (PMID: 27167827); Clin Cancer Res. 2015 Aug 15;21(16):3658-66. (PMID: 25904751); Am J Cancer Res. 2019 Jul 01;9(7):1454-1468. (PMID: 31392081); Nat Commun. 2018 Sep 18;9(1):3739. (PMID: 30228269); J Nucl Med. 2018 Apr;59(4):639-645. (PMID: 29191856); Cancer Res. 1995 Dec 1;55(23 Suppl):5935s-5945s. (PMID: 7493374); J Nucl Med. 2014 Sep;55(9):1519-24. (PMID: 24982436); Clin Cancer Res. 2017 Jun 1;23(11):2730-2741. (PMID: 28119364); Nat Med. 2011 Sep 18;17(10):1315-9. (PMID: 21926976); Dis Colon Rectum. 2018 May;61(5):547-553. (PMID: 29578919); J Gastrointest Surg. 2006 Dec;10(10):1338-45; discussion 1345-6. (PMID: 17175452); Semin Cancer Biol. 1999 Apr;9(2):67-81. (PMID: 10202129); J Nucl Med. 2017 May;58(5):706-710. (PMID: 28126888); Br J Cancer. 2013 Feb 19;108(3):662-7. (PMID: 23322207); Science. 2019 Jun 07;364(6444):952-955. (PMID: 31171691); Cell. 2018 Dec 13;175(7):1972-1988.e16. (PMID: 30550791) |
| Contributed Indexing: | Keywords: antibody; colorectal cancer; ex vivo; image-guided surgery; targeted imaging near infrared fluorescence; translational medicine |
| Entry Date(s): | Date Created: 20200423 Latest Revision: 20200928 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7226456 |
| DOI: | 10.3390/cancers12040987 |
| PMID: | 32316388 |
| Database: | MEDLINE |
Journal Article