Literature DB >> 20694579

Blood clearance kinetics, biodistribution, and radiation dosimetry of a kit-formulated integrin αvβ3-selective radiotracer 99mTc-3PRGD 2 in non-human primates.

Bing Jia1, Zhaofei Liu, Zhaohui Zhu, Jiyun Shi, Xiaona Jin, Huiyun Zhao, Fang Li, Shuang Liu, Fan Wang.   

Abstract

PURPOSE: (99m)Tc-3PRGD(2) is a (99m)Tc-labeled dimeric cyclic RGD peptide with increased receptor binding affinity and improved kinetics for in vivo imaging of integrin α(v)β(3) expression in nude mouse model. To accelerate its clinical translation, we reported here the evaluation of the kit-formulated (99m)Tc-3PRGD(2) in healthy cynomolgus primates for its blood clearance kinetics, biodistribution, and radiation dosimetry. PROCEDURES: Healthy cynomolgus primates (4.1 ± 0.7 kg, n = 5) were anesthetized, and the venous blood samples were collected via a femoral vein catheter at various time points after injection of ~555 MBq of (99m)Tc-3PRGD(2). Serial whole-body scans were performed with a dual-head single photon emission computed tomography system after administering ~555 MBq of (99m)Tc-3PRGD(2) in the non-human primates, and the radiation dosimetry estimate was calculated.
RESULTS: (99m)Tc-3PRGD(2) could be easily obtained from freeze-dried kits with high radiochemical purity (>95%) and high specific activity (~5 Ci/μmol). (99m)Tc-3PRGD(2) had a rapid blood clearance with less than 1% of the initial radioactivity remaining in the blood circulation at 60 min postinjection. No adverse reactions were observed up to 4 weeks after the repeated dosing. The whole-body images exhibited high kidney uptake of (99m)Tc-3PRGD(2) and high radioactivity accumulation in the bladder, demonstrating the rapid renal clearance of this tracer. The highest radiation doses of (99m)Tc-3PRGD(2) were found in the kidneys (13.2 ± 1.08 μGy/MBq) and the bladder wall (33.1 ± 1.91 μGy/MBq).
CONCLUSION: (99m)Tc-3PRGD(2) can be readily available using the kit formulation. This tracer is safe and well tolerated, and no adverse events occurred in non-human primates. Further clinical testing and translation of (99m)Tc-3PRGD(2) for noninvasive imaging of integrin α(v)β(3) in humans are warranted.

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Year:  2011        PMID: 20694579     DOI: 10.1007/s11307-010-0385-y

Source DB:  PubMed          Journal:  Mol Imaging Biol        ISSN: 1536-1632            Impact factor:   3.488


  13 in total

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10.  Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD.

Authors:  Roland Haubner; Wolfgang A Weber; Ambros J Beer; Eugenija Vabuliene; Daniel Reim; Mario Sarbia; Karl-Friedrich Becker; Michael Goebel; Rüdiger Hein; Hans-Jürgen Wester; Horst Kessler; Markus Schwaiger
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  31 in total

1.  Longitudinal monitoring of tumor antiangiogenic therapy with near-infrared fluorophore-labeled agents targeted to integrin αvβ3 and vascular endothelial growth factor.

Authors:  Xianlei Sun; Teng Ma; Hao Liu; Xinhe Yu; Yue Wu; Jiyun Shi; Bing Jia; Huiyun Zhao; Fan Wang; Zhaofei Liu
Journal:  Eur J Nucl Med Mol Imaging       Date:  2014-02-22       Impact factor: 9.236

2.  Evaluation of a Flexible NOTA-RGD Kit Solution Using Gallium-68 from Different 68Ge/68Ga-Generators: Pharmacokinetics and Biodistribution in Nonhuman Primates and Demonstration of Solitary Pulmonary Nodule Imaging in Humans.

Authors:  Thomas Ebenhan; Isabel Schoeman; Daniel D Rossouw; Anne Grobler; Biljana Marjanovic-Painter; Judith Wagener; Hendrik G Kruger; Mike M Sathekge; Jan Rijn Zeevaart
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3.  Noninvasive detection of human-induced pluripotent stem cell (hiPSC)-derived teratoma with an integrin-targeting agent (99m)Tc-3PRGD2.

Authors:  Yang Li; Zhaofei Liu; Chengyan Dong; Peng He; Xujie Liu; Zhaohui Zhu; Bing Jia; Fang Li; Fan Wang
Journal:  Mol Imaging Biol       Date:  2013-02       Impact factor: 3.488

4.  Comparison of [99mTc]3PRGD2 Imaging and [18F]FDG PET/CT in Breast Cancer and Expression of Integrin αvβ3 in Breast Cancer Vascular Endothelial Cells.

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5.  Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate.

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7.  (99m)Tc-Galacto-RGD2: a novel 99mTc-labeled cyclic RGD peptide dimer useful for tumor imaging.

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8.  Imaging integrin αvβ 3 and NRP-1 positive gliomas with a novel fluorine-18 labeled RGD-ATWLPPR heterodimeric peptide probe.

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9.  (99m)Tc-3P-RGD2 SPECT to monitor early response to bevacizumab therapy in patients with advanced non-small cell lung cancer.

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10.  (99m)Tc-3P-RGD2 micro-single-photon emission computed tomography/computed tomography provides a rational basis for integrin αvβ3-targeted therapy.

Authors:  Tong Fu; Wei Qu; Fan Qiu; Yan Li; Guoqiang Shao; Wei Tian; Zichun Hua; Yingjian Zhang; Feng Wang
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