scholarly journals Receptor-Targeted Fluorescence-Guided Surgery With Low Molecular Weight Agents

2021 ◽  
Vol 11 ◽  
Author(s):  
Servando Hernandez Vargas ◽  
Christie Lin ◽  
Hop S. Tran Cao ◽  
Naruhiko Ikoma ◽  
Solmaz AghaAmiri ◽  
...  

Cancer surgery remains the primary treatment option for most solid tumors and can be curative if all malignant cells are removed. Surgeons have historically relied on visual and tactile cues to maximize tumor resection, but clinical data suggest that relapse occurs partially due to incomplete cancer removal. As a result, the introduction of technologies that enhance the ability to visualize tumors in the operating room represents a pressing need. Such technologies have the potential to revolutionize the surgical standard-of-care by enabling real-time detection of surgical margins, subclinical residual disease, lymph node metastases and synchronous/metachronous tumors. Fluorescence-guided surgery (FGS) in the near-infrared (NIRF) spectrum has shown tremendous promise as an intraoperative imaging modality. An increasing number of clinical studies have demonstrated that tumor-selective FGS agents can improve the predictive value of fluorescence over non-targeted dyes. Whereas NIRF-labeled macromolecules (i.e., antibodies) spearheaded the widespread clinical translation of tumor-selective FGS drugs, peptides and small-molecules are emerging as valuable alternatives. Here, we first review the state-of-the-art of promising low molecular weight agents that are in clinical development for FGS; we then discuss the significance, application and constraints of emerging tumor-selective FGS technologies.

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Solmaz AghaAmiri ◽  
Jo Simien ◽  
Alastair M. Thompson ◽  
Julie Voss ◽  
Sukhen C. Ghosh ◽  
...  

Background. Although therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS). Methods. mAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative in vitro assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with 89Zr. In vitro binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for in vivo and ex vivo fluorescence imaging. Results. In vitro findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. In vivo and ex vivo studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. In vivo HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues. Conclusions. We showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.


Neurosurgery ◽  
2021 ◽  
Author(s):  
Andrew J Kobets ◽  
David Nauen ◽  
Amy Lee ◽  
Alan R Cohen

Abstract BACKGROUND Fluorescence-guided surgery (FGS) is under investigation as a means to improve the extent of resection for primary central nervous system (CNS) tumors. Tozuleristide, known also as “Tumor Paint,” is an investigational tumor-targeting agent covalently conjugated to a derivative of the fluorescent dye indocyanine green. OBJECTIVE To report the finding of avid intraoperative fluorescence of tozuleristide on cerebral vascular malformations. METHODS Our institution is participating in a phase 2/3 study of intraoperative near-infrared fluorescence detection of pediatric primary CNS tumors in patients receiving intravenous tozuleristide and imaged with the Canvas system. Our site enrolled 2 patients with intracranial lesions, suspected preoperatively of possibly being gliomas that proved to be cavernous vascular malformations after resection. RESULTS Each lesion had a dark blue mulberry appearance and each fluoresced avidly with tozuleristide. Each was completely resected, and the patients recovered without deficit. Pathological assessment showed cavernous angioma for both cases. Tozuleristide fluorescence is postulated to result from binding to matrix metalloproteinase-2 and annexin A2, and literature review demonstrates expression of both these ligands on multiple cerebrovascular lesions, including cavernous malformations. CONCLUSION This finding deserves further investigation to determine if tozuleristide “Tumor Paint” may have a wider role in the identification of non-neoplastic intracranial pathologies.


2017 ◽  
Vol 26 (2) ◽  
pp. 153-162 ◽  
Author(s):  
Marian Gutowski ◽  
Bérénice Framery ◽  
Martin C. Boonstra ◽  
Véronique Garambois ◽  
François Quenet ◽  
...  

2010 ◽  
Vol 20 (23) ◽  
pp. 7124-7126 ◽  
Author(s):  
Tiancheng Liu ◽  
Lisa Y. Wu ◽  
Mark R. Hopkins ◽  
Joseph K. Choi ◽  
Clifford E. Berkman

Nanomedicine ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. 511-534 ◽  
Author(s):  
Fei Liu ◽  
Fen-fen Kong ◽  
Qing-po Li ◽  
Hong Yuan ◽  
Yong-zhong Du ◽  
...  

2020 ◽  
Vol 11 (28) ◽  
pp. 7302-7307 ◽  
Author(s):  
Siddharth S. Matikonda ◽  
Joseph Ivanic ◽  
Miguel Gomez ◽  
Gabrielle Hammersley ◽  
Martin J. Schnermann

Fluoro-Coumarins are a novel class of far-red and near-infrared solvent sensitive dyes of exceptionally low molecular weight.


2021 ◽  
Vol 10 (19) ◽  
pp. 4387
Author(s):  
Joanna Polom ◽  
Leszek Kalinowski ◽  
Michele Diana ◽  
Manish Chand ◽  
Carmela Caballero ◽  
...  

Since the introduction of indocyanine green (ICG) as a fluorophore in near-infrared imaging, fluorescence visualization has become an essential tool in many fields of surgery. In the field of gynecology, recent new applications have been proposed and found their place in clinical practice. Different applications in gynecology were investigated, subcategorized, and overviewed concerning surgical applications and available dyes. Specific applications in which fluorescence-guided surgery was implemented in gynecology are described in this manuscript—namely, sentinel node biopsy, mesometrium visualization, angiography of different organs, safety issues in pregnant women, ureters visualization, detection of peritoneal metastases, targeted fluorophores for cancer detection, fluorescent contamination hysterectomy, lymphography for lower limb lymphedema prevention, tumor margin detection, endometriosis, and metastases mapping. With evolving technology, further innovative research on the new applications of fluorescence visualization in cancer surgery may help to establish these techniques as standards of high-quality surgery in gynecology. However, more investigations are necessary in order to assess if these innovative tools can also be effective to improve patient outcomes and quality of life in different gynecologic malignancies.


2020 ◽  
Vol 50 (2) ◽  
Author(s):  
Jae-Ho Han ◽  
Jaepyeong Cha

Minimally invasive intraoperative imaging plays a crucial role in delicate microsurgeries for precise operation monitoring in which fiber optic imaging can be considered as an endoscopy and surgical proximity guidance tool due to its compactness. This paper presents a near-infrared time-domain reflectometric common-path optical coherence tomography imaging technique using a bare-fiber probe mounted directly on a scanning galvanometer. The common-path setup allows the use of a freely adjustable optical path length and a disposable fiber probe, as well as eliminating the need for an additional dedicated reference optical path. Experimental results demonstrate clear discrimination between the brain tumor tissue and the normal tissue for mouse brains with the images acquired in real-time over a wide area. The proposed method enables real-time and in situ visualization of tumor resection for intraoperative imaging, and this study demonstrates the feasibility of its application to microsurgical interventions.


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