Delving into the Latest Updates on 131-I-Chlorotoxin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Peptide Conjugate Radionuclide, Therapeutic radiopharmaceuticals

Synonyms

131-I-labelled chlorotoxin

+ [3]

Target

chloride channel

Mechanism

chloride channel modulators(Chloride channel modulators), SPECT(Single-photon emission-computed tomography enhancers)

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases+ [5]

Active Indication-

Inactive Indication

Adenocarcinoma of prostateBreast CancerColorectal Cancer+ [9]

Originator Organization

TransMolecular, Inc.

Active Organization-

Inactive Organization

TransMolecular, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure

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This study is designed to evaluate the ability of intravenously (IV)administered 131-I-labeled TM-601 (chlorotoxin) to provide tumor-specific localization(via radiographic imaging) in patients with recurrent or refractory primary solid tumors with evidence of metastatic involvement. (Refractory tumors are non-responsive to standard treatment.) The safety and tolerability of IV administered 131-I-TM-601 in this patient population will be evaluated as part of this study.

Start Date01 Aug 2006

Sponsor / Collaborator

TransMolecular, Inc.

NCT00114309 / Unknown statusPhase 2

A Phase II Open-Label, Multiple-Dose Study of Intracavitary Administered 131-I-TM-601 in Adult Patients With Recurrent High-Grade Glioma

This drug is being developed to treat a type of brain cancer, glioma. This study was developed to evaluate the safety, time to disease progression and survival rates after treatment.

Start Date01 Nov 2004

Sponsor / Collaborator

TransMolecular, Inc.

100 Clinical Results associated with 131-I-Chlorotoxin

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100 Translational Medicine associated with 131-I-Chlorotoxin

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100 Patents (Medical) associated with 131-I-Chlorotoxin

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12

Literatures (Medical) associated with 131-I-Chlorotoxin

01 Dec 2012·Journal of Oncology Pharmacy PracticeQ4 · MEDICINE

Lack of tumor uptake of 131-I labeled rituximab in a patient with a CD20 positive lymphoma lesion

Q4 · MEDICINE

Article

Author: Vogel, WV ; Beijnen, JH ; Baars, JW ; Huitema, ADR ; Tran, L

Radioimmunotherapy has emerged as a treatment modality for patients with CD20 positive B-cell non-Hodgkin’s lymphoma (NHL). Prior to administration of a therapeutic dose, confirmation of uptake of the radiolabeled compound in tumor locations and calculation of an appropriate dose can be performed using a diagnostic dose and subsequent imaging. We report the case of a 69-year-old male with a relapsed mantle cell lymphoma scheduled for radioimmunotherapy, where diagnostic imaging with 131-I labeled rituximab revealed unexpected new insights with implications for treatment. Persistence of the mantle cell lymphoma in a lymph node in the left arm was demonstrated by an 18-F fluorodeoxyglucose scan. However, a scan after a diagnostic dose of 131-I labeled rituximab did not show any uptake of the tracer, even though subsequent cytological analysis unequivocally confirmed a CD20 positive B-cell population in the lesion. The administration of a therapeutic dose of 131-I labeled rituximab was therefore cancelled. We here discuss the mechanisms that may explain lack of targeting in a proven CD20-positive lymphoma and provide recommendations for further studies.

01 Mar 2007·Expert Opinion on Drug DeliveryQ2 · MEDICINE

Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601)

Q2 · MEDICINE

Review

Author: Adam N Mamelak ; Douglas B Jacoby

Targeted therapies for cancer is a rapidly advancing field, but the identification of tumor-specific ligands has proven difficult. Chlorotoxin (CTX) is a small, 36 amino acid neurotoxin isolated from the venom of the Giant Yellow Israeli scorpion Leiurus Quinquestriatus. Interestingly, the peptide has been found to preferentially bind to a variety of human malignancies, but shows little or no binding to normal human tissues. A synthetic version of this peptide (TM-601) has been manufactured and covalently linked to iodine 131 (131I-TM-601) as a means of targeting radiation to tumor cells. Preclinical studies and Phase I clinical trials have been completed in patients with recurrent glioma, a type of malignant brain tumor. These studies demonstrated that intracavitary dosing of 131I-TM-601 appears safe, minimally toxic, and binds malignant glioma with high affinity and for long durations. A Phase II trial of this agent using higher doses of radioactivity and repeated local administrations is underway. In addition, enrolment has begun in a Phase I trial evaluating whether systemically delivered 131I-TM-601 can be used to image metastatic solid tumors and primary gliomas. Due to its small size, selective tumor binding properties, minimal toxicity and relative ease of manipulation, CTX represents a potentially important targeting agent for many cancers.

01 Apr 2005·Journal of nuclear medicine : official publication, Society of Nuclear Medicine

Imaging glioma extent with 131I-TM-601.

Article

Author: Hockaday, David C ; Shen, Sui ; Mamelak, Adam N ; Colcher, David ; Alvarez, Vern ; Fiveash, John ; Raubitschek, Andrew ; Liu, An

TM-601, a 36-amino-acid peptide, selectively binds to glioma cells but not normal brain parenchyma. A phase I/II clinical trial of intracavitary 131I-TM-601 in adult patients with recurrent high-grade glioma was performed to determine the biodistribution and toxicity of this potential therapy. We evaluated imaging and biodistribution data from this trial to assess whether 131I-TM-601 might be useful in determining tumor extent.METHODSAdult patients with recurrent high-grade gliomas underwent tumor resection, implantation of an intracavitary reservoir, and a single-dose injection of 370 MBq (10 mCi) 131I-TM-601 (0.25-1.0 mg of 131I-TM-601) 2-4 wks after surgery. Total-body planar scans and whole-brain SPECT scans were obtained on days 0, 1, 2, 3, and 6-8 after injection. Postresection MR images were coregistered to the SPECT scans using image analysis software. Analysis of the rate of radioactive decay and biologic elimination from the body and at the cavity site was performed. T1-weighted with gadolinium contrast (T1-Wc), T2-weighted (T2), and SPECT volumes were estimated by stereological Cavalieri sections and compared for overlap.RESULTSNonbound 131I-TM-601 was eliminated by 48 h after injection with the remaining radiolabeled peptide bound to tumor for at least 6-8 d. Biologic decay rates from 24 to 168 h after injection were only slightly shorter than the physical decay of 131I (6.3 vs. 8.0 d). A comparison of tumor volume estimates using all 3 imaging parameters indicated that 131I-TM-601-determined tumor volumes more closely paralleled T2 volumes than T1-Wc volumes. Overlap between coregistered MRI and SPECT scans corroborated the presence of radiolabeled peptide in the vicinity of infiltrating tumor up to 168 h after injection.CONCLUSION131I-TM-601 provides a reliable estimate for primary tumor extent. Further modification of this radiopeptide with other better imaging isotopes may provide an important tool for determining tumor extent and differentiating regions of viable tumor from necrosis.

100 Deals associated with 131-I-Chlorotoxin

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External Link

KEGG	Wiki	ATC	Drug Bank
-	131-I-Chlorotoxin	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic melanoma	Phase 2	US	TransMolecular, Inc.	13 Aug 2008
Oligodendroglioma	Phase 2	US	TransMolecular, Inc.	01 Aug 2008
Adenocarcinoma of prostate	Phase 2	US	TransMolecular, Inc.	01 Aug 2006
Breast Cancer	Phase 2	US	TransMolecular, Inc.	01 Aug 2006
Colorectal Cancer	Phase 2	US	TransMolecular, Inc.	01 Aug 2006
Glioblastoma Multiforme	Phase 2	US	TransMolecular, Inc.	01 Nov 2004
Gliosarcoma	Phase 2	US	TransMolecular, Inc.	01 Nov 2004
Recurrent Malignant Glioma	Phase 2	US	TransMolecular, Inc.	01 Nov 2004
Recurrent Glioma	Phase 2	US	TransMolecular, Inc.	01 Jun 2002
Melanoma recurrent	Preclinical	US	TransMolecular, Inc.	13 Aug 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


phase II (ASCO2009)	Phase 2	Recurrent Malignant Glioma	76	<sup>131</sup>I-TM601	ighongidhj(zlsxdkkpit) = tmstcsnikl nmecqlasrk (qvzoexvdow ) View more	-	20 May 2009
ASCO2008	Not Applicable	Metastatic melanoma	7	<sup>131</sup>I-chlorotoxin	ubjeacpvvj(xqaadbhqli) = arkmqkrynr fgripwrvga (dbfgpojdol ) View more	-	20 May 2008
NCT00114309 (Pubmed)	Phase 1/2	Glioma	-	131I-TM-601	kxktbzrzni(yeopasgyia) = zabpbcwmjv kmzlcqkthz (ovrtludhdv )	-	01 Apr 2005