Delving into the Latest Updates on cRGD-ZW800-1 with Synapse

Overview

Basic Info

Drug Type

Peptide drug conjugates, Fluorophore-conjugated therapeutics

Synonyms-

Target

Integrin x αvβ1 x αvβ3 x αvβ5 x αvβ6 x αvβ8

Mechanism

Integrin modulators, αvβ1 inhibitors(Integrin alpha-V/beta-1 inhibitors), αvβ3 antagonists(Integrin alpha-V/beta-3 antagonists)

+ [4]

Therapeutic Areas

NeoplasmsMouth and Tooth DiseasesOther Diseases

Active Indication

Squamous Cell Carcinoma of Head and NeckSquamous cell carcinoma of the oral cavity

Inactive Indication-

Originator Organization

Curadel

Active Organization

Erasmus MCCuradel

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC78H106N13O16S2

InChIKeyYKVVVECWJGQERY-ZVIXCXBOSA-O

CAS Registry1239855-63-0

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Gene Sequence

Sequence Code 1507071

Pancreas as well as Cholangiocarcinoma have a dismal prognosis at time of diagnosis, due to late onset of clinical symptoms, patients present with advance disease. Complete surgical resection is the only potential curative treatment, however only a small percentage is eligible for upfront total surgical resection due to extension into anatomical related important vascular structures. Neoadjuvant chemo(radio)therapy has become the standard treatment modality for non-primary resectable disease (borderline resectable and locally advanced pancreatic cancer (LAPC)), where subsequent downstaging can make identification of the primary tumor more challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by providing real-time visualization of tumors, suspect lymph nodes and vital structures during surgery. Additional intra-operative feedback could possibly reduce the frequency of positive resection margins and increase complete removal of locally spread tumor and involved lymph nodes and could thereby improve patient outcomes as well as overall survival. cRGD-ZW800-1 is a targeted NIR-fluorophore, with specific binding capacity for integrins (αvβ3, αvβ5, αvβ6) which are overexpressed on tumor cells and tumor-associated vascular endothelium associated with neoangiogenesis.

Start Date09 Nov 2022

Sponsor / Collaborator

Academisch Ziekenhuis Leiden

NCT04191460 / RecruitingPhase 2IIT

Guided by Light: Optimizing Surgical Excision of Oral Cancer Using Real-time Fluorescence Imaging

This is a two-staged clinical trial to investigate the feasibility of intraoperative Fluorescence Imaging (FLI) to adequately assess tumor margins in patients with oral cancer using cRGD-ZW800-1.

Start Date12 Jul 2022

Sponsor / Collaborator

Erasmus MC

100 Clinical Results associated with cRGD-ZW800-1

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100 Translational Medicine associated with cRGD-ZW800-1

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100 Patents (Medical) associated with cRGD-ZW800-1

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5

Literatures (Medical) associated with cRGD-ZW800-1

01 Sep 2021·Clinical Cancer Research

NIR Fluorescence Imaging of Colon Cancer With cRGD-ZW800-1—Response

Letter

Author: Vahrmeijer, Alexander L. ; Sier, Cornelis F.M.

We thank Kossatz and Notni for their interest in our article about the use of fluorescent cRGD-ZW800-1 for visualization of tumor tissue in humans during surgery ([1][1]). Their concern seems the specificity of the tracer for integrin αvβ6, which is lower than for αvβ3, and the relation with our

01 Aug 2020·Clinical Cancer ResearchQ1 · MEDICINE

First-in-Human Assessment of cRGD-ZW800-1, a Zwitterionic, Integrin-Targeted, Near-Infrared Fluorescent Peptide in Colon Carcinoma

Q1 · MEDICINE

Article

Author: Vahrmeijer, Alexander L. ; Bijlstra, Okker D. ; Terwisscha van Scheltinga, Anton G.T. ; Holman, Fabian A. ; Deken, Marion M. ; Valentijn, A. Rob P.M. ; Hilling, Denise E. ; Bhairosingh, Shadhvi S. ; Handgraaf, Henricus J.M. ; Vuijk, Jaap ; van Esdonk, Michiel J. ; Burggraaf, Jacobus ; de Valk, Kim S. ; Mieog, J. Sven D. ; Frangioni, John V. ; March, Taryn L. ; Peeters, Koen C.M.J.

AbstractPurpose:Incomplete oncologic resections and damage to vital structures during colorectal cancer surgery increases morbidity and mortality. Moreover, neoadjuvant chemoradiotherapy has become the standard treatment modality for locally advanced rectal cancer, where subsequent downstaging can make identification of the primary tumor more challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by providing real-time visualization of tumors and vital structures during surgery.Experimental Design:We present the first-in-human clinical experience of a novel NIR fluorescent peptide, cRGD-ZW800-1, for the detection of colon cancer. cRGD-ZW800-1 was engineered to have an overall zwitterionic chemical structure and neutral charge to lower nonspecific uptake and thus background fluorescent signal. We performed a phase I study in 11 healthy volunteer as well as a phase II feasibility study in 12 patients undergoing an elective colon resection, assessing 0.005, 0.015, and 0.05 mg/kg cRGD-ZW800-1 for the intraoperative visualization of colon cancer.Results:cRGD-ZW800-1 appears safe, and exhibited rapid elimination into urine after a single low intravenous dose. Minimal invasive intraoperative visualization of colon cancer through full-thickness bowel wall was possible after an intravenous bolus injection of 0.05 mg/kg at least 2 hours prior to surgery. Longer intervals between injection and imaging improved the tumor-to-background ratio.Conclusions:cRGD-ZW800-1 enabled fluorescence imaging of colon cancer in both open and minimal invasive surgeries. Further development of cRGD-ZW800-1 for widespread use in cancer surgery may be warranted given the ubiquitous overexpression of various integrins on different types of tumors and their vasculature.

28 Mar 2017·Oncotarget

Real-time near-infrared fluorescence imaging using cRGD-ZW800-1 for intraoperative visualization of multiple cancer types

Article

Author: Vahrmeijer, Alexander L. ; Burggraaf, Jacobus ; van de Velde, Cornelis J.H. ; Sibinga Mulder, Babs G. ; Boogerd, Leonora S.F. ; Frangioni, John V. ; Valentijn, A. Rob P.M. ; Sier, Cornelis F.M. ; Bordo, Mark W. ; Handgraaf, Henricus J.M. ; Boonstra, Martin C. ; Vinkenburg-van Slooten, Maaike L. ; Kuil, Joeri ; Prevoo, Hendrica A.J.M.

Incomplete resections and damage to critical structures increase morbidity and mortality of patients with cancer. Targeted intraoperative fluorescence imaging aids surgeons by providing real-time visualization of tumors and vital structures. This study evaluated the tumor-targeted zwitterionic near-infrared fluorescent peptide cRGD-ZW800-1 as tracer for intraoperative imaging of multiple cancer types. cRGD-ZW800-1 was validated in vitro on glioblastoma (U-87 MG) and colorectal (HT-29) cell lines. Subsequently, the tracer was tested in orthotopic mouse models with HT-29, breast (MCF-7), pancreatic (BxPC-3), and oral (OSC-19) tumors. Dose-ranging studies, including doses of 0.25, 1.0, 10, and 30 nmol, in xenograft tumor models suggest an optimal dose of 10 nmol, corresponding to a human equivalent dose of 63 μg/kg, and an optimal imaging window between 2 and 24 h post-injection. The mean half-life of cRGD-ZW800-1 in blood was 25 min. Biodistribution at 4 h showed the highest fluorescence signals in tumors and kidneys. In vitro and in vivo competition experiments showed significantly lower fluorescence signals when U-87 MG cells (minus 36%, p = 0.02) or HT-29 tumor bearing mice (TBR at 4 h 3.2 ± 0.5 vs 1.8 ± 0.4, p = 0.03) were simultaneously treated with unlabeled cRGD. cRGD-ZW800-1 visualized in vivo all colorectal, breast, pancreatic, and oral tumor xenografts in mice. Screening for off-target interactions, cRGD-ZW800-1 showed only inhibition of COX-2, likely due to binding of cRGD-ZW800-1 to integrin αVβ3. Due to its recognition of various integrins, which are expressed on malignant and neoangiogenic cells, it is expected that cRGD-ZW800-1 will provide a sensitive and generic tool to visualize cancer during surgery.

100 Deals associated with cRGD-ZW800-1

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