scholarly journals NIMG-25. TRANSFERRIN RECEPTOR 1 TARGETED PET/CT AND NIFR PROBES FOR IMAGING GLIOBLASTOMA MOUSE MODELS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii152-ii152
Author(s):  
Xiang-Rong Ni ◽  
Yi-Ying Zhao ◽  
Hai-Ping Cai ◽  
Zhi-Hui Yu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Mouse Models ◽  
Transferrin Receptor ◽  
Near Infrared ◽  
Surgical Removal ◽  
Fluorescein Sodium ◽  
Guided Surgery ◽  
Transferrin Receptor 1 ◽  
Fluorescence Guided Surgery ◽  
Pet Ct

Abstract OBJECTIVE A new imaging technology that indiscriminately detects intracranial glioblastoma (GBM) can help neurosurgeons remove tumor mass completely. Transferrin receptors (TfR 1) have been widely investigated as a diagnostic and therapeutic target in GBM. A TfR 1-targeted peptide, CRTIGPSVC (CRT) can accumulate at high levels in GBM tissues. In our study, taking the advantage of CRT, we synthesized two molecular imaging probes for imaging GBM precisely. One is a PET/CT probe 18F-NOTA-CRT, and the other is a near-infrared fluorescent (NIFR) probe Cy5-CRT. METHODS We initially confirmed the overexpression of TfR 1 in most of GBM and the tumor-specific homing ability of 18F-NOTA-CRT and Cy5-CRT in orthotopic U87 GBM (TfR 1 overexpression) mouse models. We then examined the feasibility of Cy5-CRT for specially identifying the GBM tissue margin in the intracranial U87 xenografts in vivo and ex vivo. Next, we compared Cy5-CRT with the clinically used fluorescein sodium in identifying tumor margins. Finally, we used Cy5-CRT to carry out a fluorescence-guided operation on a orthotopic U87 mouse model. RESULTS Both 18F-NOTA-CRT and Cy5-CRT probes specifically accumulated in U87 GBM xenografts with TfR 1 overexpression, but not in U373 GBM xenografts with very low TfR 1 expression. Cy5-CRT detected the intracranial tumor burden with exceptional contrast, enabling fluorescence-guided GBM resection under NIFR live imaging conditions. Importantly, Cy5-CRT recognized the GBM tissue margin more clearly than fluorescein sodium. CONCLUSIONS Our probes were capable of thoroughly detecting GBM tissue in vivo imaging. For translational applications, we may screen patients before surgery by PET/CT imaging with 18F-NOTA-CRT to identify gliomas with TfR 1 overexpression. As for fluorescence-guided surgery, the TfR 1-targeted optical probe Cy5-CRT specifically differentiates tumor tissues from normal brain with high sensitivity, indicating its potential application for the precise surgical removal of GBM. Keywords: Transferrin receptor 1; PET/CT; near-infrared fluorescence imaging; glioblastoma, fluorescence-guided surgery

scholarly journals Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab®-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 984 ◽  
Author(s):  
Dmitry M. Polikarpov ◽  
Douglas H. Campbell ◽  
Lucinda S. McRobb ◽  
Jiehua Wu ◽  
Maria E. Lund ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Near Infrared ◽  
Ex Vivo ◽  
Extent Of Resection ◽  
Fluorescent Imaging ◽  
Control Group ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Specific Accumulation

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.

scholarly journals One-pot synthesis of water-soluble near-infrared fluorescence RNase A capped CuInS2 quantum dots for in vivo imaging

RSC Advances ◽  
2017 ◽  
Vol 7 (80) ◽  
pp. 50949-50954 ◽  
Author(s):  
Yue Xi ◽  
Jianjun Yang ◽  
Yunshen Ge ◽  
Shenli Zhao ◽  
Jianguang Wang ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Near Infrared ◽  
Rnase A ◽  
Water Soluble ◽  
One Pot ◽  
Guided Surgery ◽  
Nir Fluorescence ◽  
Fluorescence Guided Surgery ◽  
Cuins2 Quantum Dots

Near-infrared (NIR) quantum dots (QDs) have been treated as a promising candidate of imaging agents for NIR fluorescence-guided surgery. Here, the RNase A-CuInS2 QDs is good candidate, which performers well in gastrointestinal system imaging.

Fluorescence of Deep Infiltrating Endometriosis During Laparoscopic Surgery: A Preliminary Report on 6 Cases

2018 ◽  
Vol 25 (5) ◽  
pp. 450-454 ◽  
Author(s):  
Auriane De Neef ◽  
Guy-Bernard Cadière ◽  
Pierre Bourgeois ◽  
Romain Barbieux ◽  
Giovanni Dapri ◽  
...  
Keyword(s):  
Near Infrared ◽  
Surgical Removal ◽  
Deep Infiltrating Endometriosis ◽  
Rectal Perforation ◽  
Guided Surgery ◽  
Nir Light ◽  
Fluorescence Guided Surgery ◽  
Preliminary Study ◽  
Infiltrating Endometriosis

Background. The standard treatment of rectovaginal deep infiltrating endometriosis nodules (RVDIEN) consists in their surgical removal. RVDIEN are anatomically neovascularized. Indocyanine green (ICG) reveals vascularized structures when becoming fluorescent after exposure to near-infrared (NIR) light. This study aims to evaluate if fluorescence-guided surgery can improve the laparoscopic resection of RVDIEN, thus avoiding a rectal perforation. Materials and Methods. Patients with a symptomatic RVDIEN, scheduled for a laparoscopic rectal shaving, were enrolled in the study. Technically, the RVDIEN was targeted and removed with the help of the NIR imager device Image 1 Spies (Karl Storz GmBH & Co KG, Tuttlingen, Germany) or Visera Elite II (Olympus Europe SE & Co KG, Hamburg, Germany), after an intraoperative, intravenous injection of ICG (0.25 mg/kg). Results. Six patients underwent a fluorescence-guided laparoscopic shaving procedure for the treatment of a nonobstructive RVDIEN. Fluorescence of the RVDIEN was observed in all the patients. In one patient, once the main lesion was removed, the posterior vaginal fornix still appeared fluorescent and was removed. No intraoperative rectal perforation occurred. The postoperative hospital stay was 2 days. No postoperative rectovaginal fistula occurred within a median follow-up of 16 months (range = 2-23 months). Conclusion. In this preliminary study, fluorescence-guided laparoscopy appeared to help in separating the RVDIEN from the healthy rectal tissue, without rectal perforation. Moreover, this technique was helpful in deciding if the resection needed to be enlarged to the posterior vaginal fornix.

scholarly journals Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Solmaz AghaAmiri ◽  
Jo Simien ◽  
Alastair M. Thompson ◽  
Julie Voss ◽  
Sukhen C. Ghosh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Near Infrared ◽  
Residual Disease ◽  
Ex Vivo ◽  
Guided Surgery ◽  
Nirf Imaging ◽  
Fluorescence Guided Surgery ◽  
Imaging Results

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.

Optical imaging probes and their potential contribution to radiotracer development

2016 ◽  
Vol 55 (02) ◽  
pp. 51-62 ◽  
Author(s):  
S. Hermann ◽  
M. Schäfers ◽  
C. Höltke ◽  
A. Faust
Keyword(s):  
Optical Imaging ◽  
Fluorescent Dyes ◽  
Great Influence ◽  
Potential Contribution ◽  
Preclinical Evaluation ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Imaging Probes ◽  
Unspecific Binding

SummaryOptical imaging has long been considered a method for histological or microscopic investigations. Over the last 15 years, however, this method was applied for preclinical molecular imaging and, just recently, was also able to show its principal potential for clinical applications (e.g. fluorescence-guided surgery). Reviewing the development and preclinical evaluation of new fluorescent dyes and target-specific dye conjugates, these often show characteristic patterns of their routes of excretion and biodistribution, which could also be interesting for the development and optimization of radiopharmaceuticals. Especially ionic charges show a great influence on biodistribution and netcharge and charge-distribution on a conjugate often determines unspecific binding or background signals in liver, kidney or intestine, and other organs.Learning from fluorescent probe behaviour in vivo and translating this knowledge to radio-pharmaceuticals might be useful to further optimize emerging and existing radiopharmaceuticals with respect to their biodistribution and thereby availability for binding to their targets.

Unexpected Binding of Tozuleristide “Tumor Paint” to Cerebral Vascular Malformations: A Potentially Novel Application of Fluorescence-Guided Surgery

Neurosurgery ◽  
2021 ◽  
Author(s):  
Andrew J Kobets ◽  
David Nauen ◽  
Amy Lee ◽  
Alan R Cohen
Keyword(s):  
Near Infrared ◽  
Vascular Malformations ◽  
Cns Tumors ◽  
Matrix Metalloproteinase 2 ◽  
Cerebrovascular Lesions ◽  
Cavernous Malformations ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Cerebral Vascular Malformations ◽  
Cerebral Vascular

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.

scholarly journals SGM-101: An innovative near-infrared dye-antibody conjugate that targets CEA for fluorescence-guided surgery

2017 ◽  
Vol 26 (2) ◽  
pp. 153-162 ◽  
Author(s):  
Marian Gutowski ◽  
Bérénice Framery ◽  
Martin C. Boonstra ◽  
Véronique Garambois ◽  
François Quenet ◽  
...  
Keyword(s):  
Near Infrared ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Antibody Conjugate ◽  
Near Infrared Dye

scholarly journals Understanding the Transferrin Receptor and Cellular Iron Deficiency Outside the Erythron

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. SCI-42-SCI-42
Author(s):  
Nancy C. Andrews
Keyword(s):  
Iron Deficiency ◽  
Missense Mutation ◽  
Transferrin Receptor ◽  
Iron Uptake ◽  
Clinical Manifestations ◽  
Cell Types ◽  
Conditional Knockout ◽  
Deficiency Anemia ◽  
Transferrin Receptor 1

Our laboratory showed that mouse embryos lacking the classical transferrin receptor, Tfrc, experienced anemia, pericardial effusion and a kinking of the neural tube, but otherwise appeared to be developing normally, suggesting that Tfrc was not needed by most tissues (Levy et al. 1999). Subsequently, we reported that Tfrc was essential for hematopoiesis but seemed to be dispensable in other tissues (Ned et al., 2003). A recent paper showing that a missense mutation in the TFRC internalization motif resulted in immunodeficiency without other clinical manifestations was consistent with this idea (Jabara et al., 2016). Nonetheless, we were not entirely convinced. More than thirty years ago, Larrick and Hyman described a patient with an anti-TFRC autoantibody who suffered from a broader range of clinical problems, suggesting that TFRC might have other roles (Larrick and Hyman, 1984). To help resolve the issue, we developed mice carrying an allele of Tfrc that can be conditionally inactivated, and used Cre/lox-mediated recombination to disrupt that allele in vivo, in several key cell types. We asked two questions: (1) is Tfrc important in those cell types and, if so, (2) what are the cellular consequences of Tfrc loss? We found that some cell types do not need Tfrc but others are highly dependent upon it. Those cell types that depend upon Tfrc generally need it for iron uptake, as expected, with one exception. Tfrc is critically important for normal development of the intestinal epithelium, but our data indicate that its essential role does not involve iron uptake. While surprising in view of our earlier results, the roles of Tfrc that we have unmasked through conditional knockout experiments would not have been apparent prior to the death of global Tfrc knockout embryos in mid-gestation. Nonetheless those roles are important, and our results give insight into why iron deficiency exacerbates heart failure, how muscle iron deficiency leads to disruption of systemic carbon metabolism, and how iron deficiency, rather than iron excess, may play a role in the pathogenesis of neurodegenerative disorders. Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet. 1999;21:396-9. Ned RM, Swat W, Andrews NC. Transferrin receptor 1 is differentially required in lymphocyte development. Blood. 2003;102:3711-8. Jabara HH, Boyden SE, Chou J et al. A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency. Nat Genet. 2016;48:74-8. Larrick JW, Hyman ES. Acquired iron-deficiency anemia caused by an antibody against the transferrin receptor. N Engl J Med. 1984;311:214-8. Disclosures Andrews: Novartis: Membership on an entity's Board of Directors or advisory committees.

Sign in / Sign up

Export Citation Format

Share Document