Experimental Study on Distribution and Imaging in Colorectal Cancer

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Cancer Research

[Abstract]

Objective To explore the feasibility by using 99Tcm labeled c-myc mRNA antisense PNA to early diagnose colorectal cancer.Methods Four amino acid (G-(D)-A-G-G-) and Aba (aminobutyric acid) were linked to the 5?end of c-myc mRNA antisense PNA (GCATCGTCGCGG) by chemical synthesize, then labeled it with 99Tcm in ligands exchange method. Prepared 99Tcm labeled c-myc mRNA mismatch PNA (GCATGTCTGCGG ) in the same way as control. The quality assurance of labeling PNA was measured by high-performance liquid chromatography(HPLC).Labeling yield and radiochemi- cal purity was measured by paper chromatography. The labeling yield, radiochemical purity and stability were assessed. 99Tcm labeled c-myc mRNA antisense or mismatch PNA (37MBq) was tail intravenously injected into nude mice bearing human colorectal LS174-T cell and radionuclide imaging was performed 1,2 and 4h postinjection.The mice were killed after 1,2 and 4h postinjection imaging respectively and tissue biodistribution was measured.%ID/g and target to nontarget(T/NT)ratios were calculated.The tissue biodistribution in KM mice were dealed in the same way.Results The results of HPLC confirmed that 99Tcm was joined to the PNA, with a high radiochemical purity (>95%), and very good stability in 18 hours in vitro. It was stable in vitrio or incubating with human fresh serum. Similar results were obtained for 99Tcm labeled the c-myc mismatch PNA. Both agents through urinary excretion,and kidney and spleen uptake were highest among all tissues.The radioactivity of tumor uptaking with 99Tcm labeled antisense PNA increased with time whereas the radioactivity of tumor uptaking with 99Tcm labeled mismatch PNA decreaded.The radionuclide imaging of tumor was clearly visualized 1h postinjection of 99Tcm labeled antisense PNA,and becoming clearer slightly at 4h.however,there were little 99Tcm labeled mismatch PNA accumulated in tumor within 4h.In KM mice,the kidney,intestinal and spleen uptook more radionuclide than other tissue.Conclusions 99Tcm labeled c-myc mRNA antisense PNA exhibits excellent targeting property to the colorectal LS174-T tumor tissue,which has overexpress of c-myc oncogene,and has potential application in early diagnosis of colorectal cancer.

Title: Experimental Study on Distribution and Imaging in Colorectal Cancer Tumor-bearing Nude Mice with ?(99)Tc?m Labeled c-myc mRNA Antisense PNA

Category: Cancer Science

Filename: Experimental Study on Distribution and Imaging in Colorectal Cancer Tumor-bearing Nude Mice with ?(99)Tc?m Labeled c-myc mRNA Antisense PNA.pdf

Pages: 186

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