Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma

Wang, R. F.; Shen, Jiayun; Qiu, Fan; Zhang, C. L.

doi:10.1007/s10967-007-0704-1

Cited by 2 publications

(2 citation statements)

References 14 publications

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“…Pioneering work in this field was reported by Dewanjee MK et al in 1994, who used a 15-mer phosphorothioate antisense oligodeoxyribonucleotide labeled with 111 In to image constitutive c-myc gene expression in a murine mammary carcinoma model (17). Up to now, ASONs targeting c-MYC, P-glycoprotein (Pgp), CCND1, mdr1, bcl-2, k-ras, unr, IgV H FR1 mRNA, and so forth have been chosen to be labeled with radionuclides such as 99m Tc, 111 In, 68 Ga, 64 Cu, 131 I and so forth (18)(19)(20)(21)(22)(23)(24)(25)(26), whose results all facilitate the development of antisense imaging. Despite an extensive literature search, we failed to find any research publication describing in vivo imaging of hTERT expression by antisense technology.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Imaging of Human Telomerase Reverse Transcriptase (hTERT) Messenger RNA with 99mTc-Radiolabeled Antisense Probes in Malignant Tumors

Liu¹,

Wang²,

Zhang³

et al. 2007

Journal of Nuclear Medicine

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The expression of human telomerase reverse transcriptase (hTERT) is present in most malignant cells (.85%) but is undetectable in most normal somatic cells. Visualization of hTERT expression using radionuclide targeting can provide important diagnostic information in malignant tumors. The overall aim of this study was to evaluate whether 99m Tc-radiolabeled antisense oligonucleotide (ASON) targeting hTERT messenger RNA (mRNA) can be used for imaging of hTERT expression in vivo. Methods: One 18-mer antisense or sense uniformly phosphorothioate-modified oligonucleotide targeting hTERT mRNA was radiolabeled with 99m Tc through the bifunctional chelator N-hydroxysuccinimidyl derivative of S-acetylmercaptoacetyltriglycine (S-acetyl NHS-MAG3). Then the radiolabeled probe was characterized in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to assay the mRNA level after proliferating cells had been incubated with the antisense and sense probes. 99m Tc-MAG3-ASON or 99m Tc-MAG3-SON was injected intravenously in mammary tumor-bearing BALB/c nude mice. Biodistribution and in vivo imaging was performed periodically. All data were analyzed by statistical software. Results: The labeling efficiencies of 99m Tc-MAG3-ASON/SON reached 76% 6 5% (n 5 5) within 15-30 min at room temperature, the specific activity was up to 1,850 kBq/mg, and the radiochemical purity was .96% after purification. 99m Tc-MAG3-ASON showed complete stability at room temperature and in fresh 37°C human serum. In comparison with 99m Tc-MAG3-SON, 99m Tc-MAG3-ASON preserved the capacity to bind living hTERT-expressing cells specifically and to inhibit the expression of hTERT mRNA significantly as well as ASON. In nude mice bearing hTERT-expressing MCF-7 xenografts, tumor radioactivity uptake of 99m Tc-MAG3-ASON after injection was significantly higher than that of 99m Tc-MAG3-SON after injection (P , 0.05). The hTERT-expressing xenografts were clearly imaged at 4-8 h noninvasively after injection of 99m Tc-MAG3-ASON, whereas the xenografts were not imaged at any time after injection of 99m Tc-MAG3-SON. Conclusion: This in vivo study provides evidence that 99m Tc-MAG3-ASON targeting hTERT mRNA can be used as a potential candidate for visualization of hTERT expression in carcinomas.

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Section: Discussionmentioning

confidence: 99%

Noninvasive Imaging of Human Telomerase Reverse Transcriptase (hTERT) Messenger RNA with 99mTc-Radiolabeled Antisense Probes in Malignant Tumors

Liu¹,

Wang²,

Zhang³

et al. 2007

Journal of Nuclear Medicine

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“…Visualization of hTERT expression using radionuclide labeled tracers can provide important diagnostic information and prognostic value in malignant tumors. Recently, 131 I-and 99m Tc-labeled antisense oligonucleotide ( 99m Tc-MAG 3 -ASON) targeting hTERT mRNA have been reported [76,77]. The radiotracer preserved the capacity to bind living hTERT-expressing cells specifically and to inhibit the expression of hTERT mRNA significantly as well as ASON.…”

Section: Potential Radiotracers For Imaging Of Human Telomerase Revermentioning

confidence: 99%

Radiopharmaceuticals in China: current status and prospects

Jia¹,

Liu

2014

Radiochimica Acta

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The review provides an overview of the current status of radiopharmaceuticals in China for in vivo clinical use and also describes some important advances in the past three decades. Development of the diagnostic and therapeutic radiopharmaceuticals as well as basic research on radiopharmaceutical chemistry are being introduced. The radiotracers developed in China include: (1) Brain perfusion imaging agents and CNS radiotracers for -amyloid plaques, 1 receptors, and dopamine D 2 or D 4 receptors;(2) 99m Tc-and 18 F-labeled myocardial perfusion imaging agents; (3) tumor imaging agents including integrin-targeting radiotracer, novel sentinel lymph node imaging agents, hypoxia imaging agents, 99m Tc-labeled glucose derivatives, 2 receptor imaging agents, folate receptor imaging agents, and potential radiotracers for imaging of human telomerase reverse transcriptase expression; (4) Potential infection imaging agents; (5) Potential asialoglycoprotein receptor imaging agents; (6) Other imaging agents. Moreover, some prospects of research and development of radiopharmaceuticals in the near future are discussed.

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Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma

Cited by 2 publications

References 14 publications

Noninvasive Imaging of Human Telomerase Reverse Transcriptase (hTERT) Messenger RNA with 99mTc-Radiolabeled Antisense Probes in Malignant Tumors

Noninvasive Imaging of Human Telomerase Reverse Transcriptase (hTERT) Messenger RNA with 99mTc-Radiolabeled Antisense Probes in Malignant Tumors

Radiopharmaceuticals in China: current status and prospects

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