scholarly journals Fluorescent Thienothiophene-Containing Squaraine Dyes and Threaded Supramolecular Complexes with Tunable Wavelengths between 600–800 nm

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2229 ◽  
Author(s):  
Wenqi Liu ◽  
Hannah McGarraugh ◽  
Bradley Smith

A new family of fluorescent thiophene and thienothiophene-containing squaraine dyes is described with tunable wavelengths that cover the absorption/emission range of 600–800 nm. The deep-red and near-infrared fluorescent compounds were easily prepared by simple synthesis and purification methods. Spectral studies showed that each squaraine was rapidly encapsulated by a tetralactam macrocycle, with nanomolar affinity in water, to produce a threaded supramolecular complex with high chemical stability, increased fluorescence quantum yield, and decreased fluorescence quenching upon dye self-aggregation. Energy transfer within the supramolecular complex permitted multiplex emission. That is, two separate dyes with fluorescence emission bands that match the popular Cy5 and Cy7 channels, could be simultaneously excited with a beam of 375 nm light. A broad range of practical applications is envisioned in healthcare diagnostics, microscopy, molecular imaging, and fluorescence-guided surgery.

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 ◽  
...  

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.


Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 984 ◽  
Author(s):  
Dmitry M. Polikarpov ◽  
Douglas H. Campbell ◽  
Lucinda S. McRobb ◽  
Jiehua Wu ◽  
Maria E. Lund ◽  
...  

Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab®, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab® was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab®-IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 ± 2.8. The average TBR over the 10-day period was 5.8 ± 0.6 in mice injected with Miltuximab®-IR800 versus 2.4 ± 0.1 for the control group injected with IgG-IR800 (p = 0.001). Ex vivo assessment of Miltuximab®-IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab®-IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.


BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
P. B. A. A. van Driel ◽  
M. C. Boonstra ◽  
H. A. J. M. Prevoo ◽  
M. van de Giessen ◽  
T. J. A. Snoeks ◽  
...  

BMC Surgery ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sachiyo Shirakawa ◽  
Hirochika Toyama ◽  
Masahiro Kido ◽  
Takumi Fukumoto

Abstract This is the response article to correspondence article received for our published article in BMC surgery titled “A prospective single-center protocol for using near-infrared fluorescence imaging with indocyanine green during staging laparoscopy to detect small metastasis from pancreatic cancer”. Peter L. Labib, MBChB pointed out the necessity to administer indocyanine green intravenously in separate timing for detection of metastasis in liver and peritoneum. Preoperative injection is suitable to detect hepatic metastasis and intraoperative injection is reported to be well suited to detect peritoneal metastasis. However, we could not find the usefulness of intraoperative injection of indocyanine green for detecting peritoneal metastasis in cases with staging laparoscopy prior to this study. We employed this study protocol with only preoperative injection of indocyanine green to simplify the procedure with consideration of probably more frequent cases of hepatic metastasis that is difficult to detect with white-light imaging than those of peritoneal metastasis.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lianne M. Wellens ◽  
Marion M. Deken ◽  
Cornelis F. M. Sier ◽  
Hannah R. Johnson ◽  
Fàtima de la Jara Ortiz ◽  
...  

Abstract Neuroblastoma resection represents a major challenge in pediatric surgery, because of the high risk of complications. Fluorescence-guided surgery (FGS) could lower this risk by facilitating discrimination of tumor from normal tissue and is gaining momentum in adult oncology. Here, we provide the first molecular-targeted fluorescent agent for FGS in pediatric oncology, by developing and preclinically evaluating a GD2-specific tracer consisting of the immunotherapeutic antibody dinutuximab-beta, recently approved for neuroblastoma treatment, conjugated to near-infrared (NIR) fluorescent dye IRDye800CW. We demonstrated specific binding of anti-GD2-IRDye800CW to human neuroblastoma cells in vitro and in vivo using xenograft mouse models. Furthermore, we defined an optimal dose of 1 nmol, an imaging time window of 4 days after administration and show that neoadjuvant treatment with anti-GD2 immunotherapy does not interfere with fluorescence imaging. Importantly, as we observed universal, yet heterogeneous expression of GD2 on neuroblastoma tissue of a wide range of patients, we implemented a xenograft model of patient-derived neuroblastoma organoids with differential GD2 expression and show that even low GD2 expressing tumors still provide an adequate real-time fluorescence signal. Hence, the imaging advancement presented in this study offers an opportunity for improving surgery and potentially survival of a broad group of children with neuroblastoma.


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