Delving into the Latest Updates on 99mTc-3P4-RGD2 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

technetium-99m-(polyethylene glycol-4)3-(Arg-Gly-Asp)2

Target

αvβ3

Action

modulators

Mechanism

αvβ3 modulators(Integrin alpha-V/beta-3 modulators)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [2]

Active Indication-

Inactive Indication

Breast CancerEsophageal CarcinomaLung Cancer+ [1]

Originator Organization

Peking University

Active Organization-

Inactive Organization

Stanford University

First Affiliated Hospital Of Fujian Medical UniversityBeijing Xiehe Bioengineering United Company

+ [2]

License Organization-

Drug Highest PhaseDiscontinuedClinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC117H162N28NaO44PS3Tc

InChIKeyLYBFHKSSSDZWIX-INZTZQCYSA-I

CAS Registry1219467-97-6

Sequence Code 95090

Sequence Code 565009095

Some thyroid-disrupting chemicals (TDCs) affect thyroid function by activating the pathways mediated by a typical thyroid hormone (TH) membrane receptor, integrin α_vβ₃. The present study introduces improved competitive binding assays for the rapid and sensitive evaluation of the binding affinities of TDCs for integrin α_vβ_3. Based on different probes, two assays were modified: a fluorescence competitive binding assay and a radioligand competitive binding assay. The chemicals tested included the known TH, 3,3',5,5'-tetraiodo-l-thyronine (T4); a deaminated analog of T4, tetraiodothyroacetic acid (tetrac); and phthalate esters (PAEs). The relative binding potency of T4 was studied, and the concentration required to displace 50% of the ligands from their receptors (RIC50) of T4 was 4.9 × 10⁵ and 9.7 × 10⁴ nM for the fluorescence and radioligand competitive binding assays, respectively, suggesting that the radioligand competitive binding assay might be more sensitive for the evaluation of the binding affinity for integrin α_vβ₃. The three PAEs, including diethyl hexyl phthalate (DEHP), benzyl butyl phthalate (BBP) and dibutyl phthalate (DnBP), demonstrated binding affinities for integrin α_vβ₃ in the following order of potency: DnBP > DEHP > BBP tested by the radioligand competitive binding assay. A docking simulation of each of the three PAEs with integrin α_vβ₃ confirmed the calculated binding energies, which had a strong positive relationship with the log RIC20 values of the 3 PAEs (R = 0.99, p < 0.001). The present study shows that the established radioligand competitive binding assay could be used as a valuable tool for quantifying the affinity of TDCs for integrin α_vβ₃.

01 Jun 2017·Nuclear medicine and biologyQ4 · MEDICINE

99m Tc-3PRGD2 scintigraphy to stage liver fibrosis and evaluate reversal after fibrotic stimulus withdrawn

Q4 · MEDICINE

Article

Author: Xu, Weina ; Zhao, Zhoushe ; Liu, Changping ; Cao, Li ; Yu, Shupeng ; Guo, Qiyong ; Xin, Jun ; Zhang, Xin ; Yang, Zhiguang ; Shi, Yu

OBJECTIVE:

Scintigraphy using 99mTc-3PRGD2 targeting integrin αvβ3 could assess activation of hepatic stellate cells (HSCs). Liver fibrogenesis is intimately associated with activation of HSCs, and the fibrolytic process is accompanied by the reduction of the activated HSCs. In this study, we aimed to evaluate the feasibility of this method to assess the severity of liver fibrosis and the reversal after the fibrotic stimulus withdrawal.

METHODS:

Liver fibrosis of different stages was induced by thioacetamide (TAA) injection for 2, 4 and 6 weeks (n = 6 for each time point). Another 6 rats with 8-week TAA administration (the 8-week group) and 6 rats which were injected with TAA for 6 weeks, and then withdrawn of TAA for 2 weeks (spontaneous recovery rats, SRR) were designed. The ratios of radioactivity detected in the liver vs. the heart at 30 min post-injection of ^99mTc-3PRGD2 (L/H30_min), the collagen proportionate area (CPA), the protein and mRNA levels of integrin α_v, integrin β₃ were analyzed and compared among groups.

RESULTS:

The Ishak stage scores of the livers in the control and 2, 4, 6-week groups increased when the TAA administration period was extended. L/H30_min increased with the upgrading of liver fibrosis and the differences between each pair of groups were statistically significant (p 30 min in the 8-week group was similar to that in the 6-week group (p > 0.05), but was significantly higher than that in the SRR group (p = 0.005).

CONCLUSIONS:

Scintigraphy using ^99mTc-3PRGD2 may provide a non-invasive method for grading liver fibrosis and assessing liver fibrosis reversal.

07 Feb 2017·Cancer investigationQ4 · MEDICINE

Evaluation of Tc-99m-3PRGD2 Integrin Receptor Imaging in the Differential Diagnosis of Breast Lesions and Comparison With Mammography

Q4 · MEDICINE

Article

Author: Chordia, Mahendra D. ; Jia, Bing ; Ouyang, Zhong ; Chen, Guibing ; Wang, Fan ; Wu, Hua

PURPOSE:

The aims of this study were to evaluate and compare efficacies of Tc-99m-3PRGD2 integrin receptor imaging under variety of conditions for the diagnosis of breast lesions, in addition to comparison with mammography.

MATERIALS AND METHODS:

Seventy-two female patients with established breast lesions were recruited. All patients were examined by Tc-99m-3PRGD2 integrin receptor imaging and mammography. Whole-body scan and SPECT/CT were acquired at dual time points of 2 and 4 h after injection using standard protocol. The processed images were evaluated by visual and semi-quantitative analysis. Mammography was performed using up and down and internal and external oblique views. The gold standard of diagnosis was based on histopathological findings.

RESULTS:

Sensitivity greater than 85.0% and accuracy greater than 80.0% were observed under any technical method. For dense mammary gland, the sensitivity, specificity, and accuracy of Tc-99m-3PRGD2 SPECT/CT 4-h imaging and mammography were 95.2, 75.0, and 90.7%, and 71.4, 58.3, and 68.5% respectively. Combined two methods' sensitivity, specificity, and accuracy for detection of breast cancer can reach 98.3, 86.7, and 96.0%.

CONCLUSIONS:

Tc-99m-3PRGD2-based molecular imaging is a sensitive method for the differential diagnosis of breast lesions. Particularly, Tc-99m-3PRGD2-SPECT/CT has better diagnostic value in dense mammary gland as compared with mammography. Combining two methods can significantly improve the diagnostic efficiency.

100 Deals associated with 99mTc-3P4-RGD2

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Clinical	-	Purdue University	-
Breast Cancer	Clinical	-	Stanford University	-
Breast Cancer	Clinical	-	Beijing Xiehe Bioengineering United Company	-
Breast Cancer	Clinical	-	Peking University	-
Breast Cancer	Clinical	-	First Affiliated Hospital Of Fujian Medical University	-
Esophageal Carcinoma	Clinical	-	Stanford University	-
Esophageal Carcinoma	Clinical	-	Purdue University	-
Esophageal Carcinoma	Clinical	-	Beijing Xiehe Bioengineering United Company	-
Esophageal Carcinoma	Clinical	-	Peking University	-
Esophageal Carcinoma	Clinical	-	First Affiliated Hospital Of Fujian Medical University	-