Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma
- VernacularTitle:放射性碘标记反义寡核苷酸在荷人淋巴瘤裸鼠中的分布及显像研究
- Author:
Jing SHEN
;
Rong-Fu WANG
;
Chun-Li ZHANG
;
Meng LIU
;
Feng-Qin GUO
;
- Publication Type:Journal Article
- Keywords:
Lymphoma;
Ohgonucleotides antisense;
Iodine radioisotopes;
Isotopelabeling
- From:
Journal of Peking University(Health Sciences)
2003;0(06):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the possibility of using radioiodine labeled framework region(FR)antisense oligonucleotides(ASONs)as an imaging agent or antisense therapeutic radiopharmaceu-tical in lymphoma.Methods:A 18-mer partial phosphorothioate oligonucleotide sequence was synthe-sized and grafted in 5'with a tyramine group which was further radioiodinated.Radioiodination of the tyra-mine derivatized oligonucleotides was performed using the chloramine T method.(1)Normal CD-1 micewere injected via a tail vein with 148 kBq (125)~I-FR-ASON(2-3?g).Animals were sacrificed at the endof 1,2,4 and 24h,and tissue samples were studied.(2)Liposome-mediated 3.33 MBq (131)I-FR-ASON(7-9?g)were injected intralumorally into tumor-bearing BALB/c mice(6 weeks after innculation of10~7 Namalwa cells)meanwhile liposome-mediated (131)~I labeled sense oligonucleotides served as controls.Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24h afterinjection.Percentage of the injected dose per gram of tumor and tumor/non-tumor tissue ratios(T/NT)were calculated tot each group of mice and the difference between two groups was assessed.Results:The5′tyramine group allowed specific and stable radinlabeling of the ASON with radioiodine.The radioactivi-ty reached its peak 1h after injection,and then decreased rapidly in normal mice after intravenous ad-ministration of (125)~I-FR-ASON.The liver,stomach and intestine played an important role in biodistributionand radioactivity counts were low in bone,brain and blood.When (131)I-FR-ASON was injected intratumor-ally into mice grafted with Namalwa cell line,images showed the tracer accumulated in the tumor,Imme-diately after intratumoral administration,only the tumor was visible.Scintiscans performed at the end of 1and 2h showed elimination of the tracer from the tumor to the abdomen and at the end of 24h the tumorwas 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 FRASON showed high specificity in V1 family B-cell lymphoma,which should be further investigated for nu-clear medicine imaging application and radionuclide antisense therapy.
