Blood Clearance Kinetics, Biodistribution, and Radiation Dosimetry of a Kit-Formulated Integrin αvβ3-Selective Radiotracer 99mTc-3PRGD2 in Non-Human Primates

Jia, Bing; Liu, Zhaofei; Zhu, Zhaohui; Shi, Jiyun; Jin, Xiaona; Zhao, Hang; Li, Fang; Liu, Shuang; Wang, Fan

doi:10.1007/s11307-010-0385-y

Cited by 68 publications

(85 citation statements)

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“…Cyclic RGD peptide dimer 3PRGD2 was custom-made by Peptides International, Inc. Na 99m TcO4 was obtained from a commercial 99 Mo/ 99m Tc generator (Beijing Atom High Tech Co., Ltd.). Synthesis of the labeling precursor, kit preparation, and subsequent 99m Tc labeling were performed as previously described (17). Briefly, the kit for preparation of 99m Tc-3PRGD2 was formulated by combining 20 mg of hydrazinonicotinamide-3PRGD2, 5 mg of TPPTS, 6.5 mg of tricine, 40 mg of mannitol, 38.5 mg of disodium succinate hexahydrate, and 12.7 mg of succinic acid.…”

Section: Radiosynthesis Of 99m Tc(hydrazinonicotinamide-3prgd2)(tricimentioning

confidence: 99%

“…99m Tc-PEG 4 -E [PEG 4 -c(RGDfK)] 2 ( 99m Tc-3PRGD2) is a new 99m Tc-labeled cyclic RGD dimer peptide with increased receptor binding affinity and improved kinetics for the in vivo imaging of integrin a v b 3 expression in xenografted tumor-bearing models (6,15,16). The blood clearance kinetics, biodistribution, and radiation dosimetry of a kit-formulated 99m Tc-3PRGD2 were also evaluated in nonhuman primates in our department, and no adverse reactions were observed to date (17). A multicenter study of 99m Tc-3PRGD2 for integrin receptor imaging of lung cancer was sponsored by our department last year.…”

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confidence: 99%

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Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2

Zhao

Jin

et al. 2012

J Nucl Med

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Integrin a v b 3 has been proposed as a potential imaging target for radiolabeled RGD peptides and a molecular marker for the estimation of tumor angiogenesis, yet it has not been applied in differentiated thyroid cancer (DTC) patients with radioactive iodine-refractory (RAIR) lesions. The current study was conducted to assess the potential of integrin a v b 3 imaging in the detection of RAIR DTC lesions using 99m Tc-PEG 4 -E [PEG 4 -c(RGDfK)] 2 ( 99m Tc-3PRGD2), thus providing a feasible antiangiogenetic therapeutic target. Methods: Ten DTC patients (2 men, 8 women; mean age 6 SD, 56.4 6 9.8 y; age range, 42-73 y) with multiple RAIR metastases were recruited; all patients had both elevated thyroglobulin levels (thyroglobulin-positive) and negative 131 I whole-body scan (WBS) results. Clinical data were collected including history, 131 I WBS, contemporary CT, ultrasonography, thyroid-stimulating hormone, thyroglobulin, and antithyroglobulin. One or 2 target lesions were selected on the contemporary CT images using Response Evaluation Criteria in Solid Tumors 1.0 for all patients, 7 of whom were chosen for the calculation of the rates of lesion growth within the 3 mo before the study. WBS at 30 min and regional SPECT for lesions at 1 h were performed after the intravenous injection of 99m Tc-3PRGD2. Two experienced nuclear medicine physicians read the images in a masked fashion. The tumor-to-background ratios were calculated for further analysis. Results: All the target RAIR metastatic lesions were identified as positive on 99m Tc-3PRGD2 SPECT images. There was a significant correlation between the mean tumor-to-background ratios and mean growth rates of target lesions (r 5 0.878, P 5 0.009). Conclusion: The RAIR ( 131 I WBS-negative/thyroglobulin-positive) metastatic lesions can be traced using 99m Tc-3PRGD2 imaging, meaning these lesions are highly neovascularized. 99m Tc-3PRGD2 angiogenesis imaging can be used for the localization and growth evaluation of RAIR lesions, providing a new therapeutic target and a novel imaging modality to monitor the efficacy of certain antiangiogenetic therapy.

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Section: Radiosynthesis Of 99m Tc(hydrazinonicotinamide-3prgd2)(tricimentioning

confidence: 99%

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confidence: 99%

Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2

Zhao

Jin

et al. 2012

J Nucl Med

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“…Over the last several years, there has been interest in radiolabeled multimeric cyclic RGD peptides as radiotracers for tumor imaging by SPECT or PET (Shi et al, 2009aChakraborty et al, 2010;Zhou et al, 2012a TcO 4 -with high specific activity using a kit formulation, making it easily accessible (Wang et al, 2009;Jia et al, 2011). In several preclinical models, 99m Tc-3P-RGD 2 showed high tumor uptake, rapid renal clearance, and high metabolic stability (Wang et al, 2009;Jia et al, 2011;Zhou et al, 2011). Tc-3P-RGD 2 tumor uptake measured by percent injected dose (%ID)/cm 3 and tumor-to-muscle (T/M) ratio had a linear correlation with tumor b 3 and CD31, a marker for tumor blood vessels (Zhou et al, , 2012a.…”

Section: Introductionmentioning

confidence: 99%

Monitoring Tumor Response to Linifanib Therapy with SPECT/CT Using the Integrinα_vβ₃–Targeted Radiotracer^99mTc-3P-RGD₂

Zhou

Voorbach

et al. 2013

J Pharmacol Exp Ther

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The objective of this study was to determine the utility of Tc-3P-RGD 2 SPECT/CT imaging was performed at baseline (-1 day) and days 1, 4, 11, and 18. Tumors were harvested at all imaging time points for histopathological analysis with H&E and immunohistochemistry. A significant difference in tumor volumes between vehicle-and linifanib-treated groups was observed after 4 days of linifanib therapy in the U87MG model. The percent injected dose (%ID) tumor uptake of 99m Tc-3P-RGD 2 peaked in the vehicle-treated group at day 11, while the %ID/cm 3 tumor uptake decreased slowly over the whole study period. During the first 2 days of linifanib treatment, a rapid decrease in both % ID/cm 3 tumor uptake and tumor/muscle ratios of 99m Tc-3P-RGD 2 was observed, followed by a slow decrease until day 18. No decrease in tumor uptake of 99m Tc-3P-RGD 2 or tumor volume was observed for either treatment group in the PC-3 model. Changes in tumor vasculature were confirmed by histopathological H&E analysis and immunohistochemistry. Longitudinal imaging using 99m Tc-3P-RGD 2 SPECT/CT may be a useful tool for monitoring the downstream biologic effects of linifanib therapy.

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“…It shows high tumor uptake, rapid blood and renal clearance, and radiotracer accumulation in the bladder. 9 Preparation of 99m Tc-3P-RGD 2 99m Tc-3P-RGD 2 was prepared according to previously reported methods 19 using a lyophilized kit formulation containing 20-lg HYNIC-3P-RGD 2 , 5-mg TPPTS, 6.5-mg tricine, 40-mg mannitol, 38.5-mg disodium succinate hexahydrate, and 12.7-mg succinic acid.…”

Section: Animal Modelmentioning

confidence: 99%

“…4,5 The RGD peptide (Arg-Gly-Asp), which selectively targets integrin a v b 3 , is a biomolecule that accelerates the binding of radionuclide particles, including 64 Cu, 111 In, 18 F, 99m Tc, and 68 Ga, [6][7][8] to integrin a v b 3 , thereby enabling imaging of a v b 3 -positive tumors with PET and single-photon emission computed tomography (SPECT) with high accuracy. 6 The 99m Tc-3P-RGD 2 tracer, which is characterized by rapid blood clearance and urinary system excretion, 9 has been demonstrated to be more effective than 99m Tc-RGD 2 , 99m Tc-P-RGD 2 , 99m Tc-2P-RGD 2 , or 99m Tc-3G-RGD 2 . [10][11][12] Besides its diagnostic role, RGD is an important agent in cancer treatment.…”

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^99mTc-3P-RGD₂ Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin α_vβ₃-Targeted Therapy

Qiu

et al. 2014

Cancer Biotherapy and Radiopharmaceuticals

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Purpose: This study was to demonstrate the utility of 99m Tc-3P-RGD 2 micro-single-photon emission computed tomography/computed tomography (SPECT/CT) for the integrin a v b 3 expression quantification in NCI-H446 and A549 lung cancer xenografts. Materials and Methods: 99m Tc-3P-RGD 2 was prepared with high radiochemical purity (97% -2%) and showing high in vitro stability. The in vitro affinities of 99m Tc-3P-RGD 2 to NCI-H446 and A549 tumor cells were analyzed with c-counter, while the in vivo uptakes in NCI-H446 and A549 xenografts were evaluated with micro-SPECT/CT. The region of interest was drawn over the tumor site and contralateral muscle on the SPECT/ CT image, and the tumor to nontumor (T/NT) ratio was calculated to estimate a v b 3 expression and tumor uptake. The expressions of integrin a v b 3 in vitro and in vivo were analyzed using a flow cytometer and immunofluorescence. Results: Micro-SPECT/CT demonstrated focal uptake in the tumors. T/NT ratio in NCI-H446 xenografts was significantly higher compared with the A549 tumor model, as 5.92 -0.82 and 3.62 -0.91, respectively, with p < 0.05. In addition, integrin a v b 3 expression in NCI-H446 cells was significantly higher compared with the A549 cells, which was consistent with the imaging data. A linear relationship was observed between 99m Tc-3P-RGD 2 uptake and a v b 3 expression (R 2 = 0.7667, p < 0.001). Conclusion:99m Tc-3P-RGD 2 SPECT/CT could be used to quantify integrin a v b 3 expression within tumors, providing a rational basis for integrin a v b 3 -targeted cancer therapy.

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Blood Clearance Kinetics, Biodistribution, and Radiation Dosimetry of a Kit-Formulated Integrin αvβ3-Selective Radiotracer 99mTc-3PRGD2 in Non-Human Primates

Cited by 68 publications

References 12 publications

Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2

Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2

Monitoring Tumor Response to Linifanib Therapy with SPECT/CT Using the Integrinα_vβ₃–Targeted Radiotracer^99mTc-3P-RGD₂

^99mTc-3P-RGD₂ Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin α_vβ₃-Targeted Therapy

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Blood Clearance Kinetics, Biodistribution, and Radiation Dosimetry of a Kit-Formulated Integrin αvβ3-Selective Radiotracer 99mTc-3PRGD2 in Non-Human Primates

Cited by 68 publications

References 12 publications

Integrin αvβ3 Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using 99mTc-3PRGD2

Integrin αvβ3 Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using 99mTc-3PRGD2

Monitoring Tumor Response to Linifanib Therapy with SPECT/CT Using the Integrinαvβ3–Targeted Radiotracer99mTc-3P-RGD2

99mTc-3P-RGD2 Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin αvβ3-Targeted Therapy

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Product

Resources

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Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2

Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2

Monitoring Tumor Response to Linifanib Therapy with SPECT/CT Using the Integrinα_vβ₃–Targeted Radiotracer^99mTc-3P-RGD₂

^99mTc-3P-RGD₂ Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin α_vβ₃-Targeted Therapy