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  • Title: [Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma].
    Author: Shen J, Wang RF, Zhang CL, Liu M, Guo FQ.
    Journal: Beijing Da Xue Xue Bao Yi Xue Ban; 2004 Dec; 36(6):655-9. PubMed ID: 15605104.
    Abstract:
    OBJECTIVE: To investigate the possibility of using radioiodine labeled framework region (FR) antisense oligonucleotides (ASONs) as an imaging agent or antisense therapeutic radiopharmaceutical in lymphoma. METHODS: A 18-mer partial phosphorothioate oligonucleotide sequence was synthesized and grafted in 5' with a tyramine group which was further radioiodinated. Radioiodination of the tyramine derivatized oligonucleotides was performed using the chloramine T method. (1) Normal CD-1 mice were injected via a tail vein with 148 kBq (125)I-FR-ASON (2-3 microg). Animals were sacrificed at the end of 1, 2, 4 and 24 h, and tissue samples were studied.(2) Liposome-mediated 3.33 MBq (131)I-FR-ASON (7-9 microg) were injected intratumorally into tumor-bearing BALB/c mice (6 weeks after inoculation of 107 Namalwa cells) meanwhile liposome-mediated (131)I labeled sense oligonucleotides served as controls. Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24 h after injection. Percentage of the injected dose per gram of tumor and tumor/non-tumor tissue ratios (T/NT) were calculated for each group of mice and the difference between two groups was assessed. RESULTS: The 5' tyramine group allowed specific and stable radiolabeling of the ASON with radioiodine. The radioactivity reached its peak 1 h after injection, and then decreased rapidly in normal mice after intravenous administration of (125)I-FR-ASON. The liver, stomach and intestine played an important role in biodistribution and radioactivity counts were low in bone, brain and blood. When (131)I-FR-ASON was injected intratumorally into mice grafted with Namalwa cell line, images showed the tracer accumulated in the tumor. Immediately after intratumoral administration, only the tumor was visible. Scintiscans performed at the end of 1 and 2 h showed elimination of the tracer from the tumor to the abdomen and at the end of 24 h the tumor was clearly seen. Percentage of the injected dose per gram of tumor and T/NT ratios for the sense group (control) were significantly lower than those of the antisense group. CONCLUSION: Radiolabeled Ig FR ASON showed high specificity in V1 family B-cell lymphoma, which should be further investigated for nuclear medicine imaging application and radionuclide antisense therapy.
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