| Objective: To evaluate the killing effects of 5-iodo-2'-deoxyuridine(UdR) in human pancreatic cancer cell line Bax-Pc in vitro; To analyzethe factors which affect the uptake of 125I-UdR and investigate thedistribution, therapeutic effect and safety of 5-[125I]iodo-2'-deoxyuridine(125I-UdR) in Balb/c nude mice bearing pancreatic cancer .Methods: (l)The amount of 125I-UdR in cells and caryons was determined after incubated for 0.25-84 hours in RPMI1640 culturing medium containing different radioactive concentrations of 125I-UdR. The killing effects of 125I-UdR on Bax-Pc were estimated through colony-forming assay.(2)After intratumoiirally injected, the distribution of 125I-UdR in nude mice was estimated by SPECT scintigraphy and the radioactivities in various organs were determined by Y well counter. The antineoplastic capabilities were demonstrated through estimating the general pathological and cellular changes of tumour , as well as analyzing the survival rate. The pharmic safety was evaluated by using hemogram, marrow cell and flow biochemistry indexes: AlanineAminotransferase(ALT), Aspartate Aminotransferase (AST), blood urea nitrogen(BUN) and creatinine (Cr) .Results: (1) The uptake of 125I-UdR by Bax-Pc cells was higher than that of Na125I (PO.01). The amount of 125I-UdR in cells and caryons correlated with the escalation of the radioactive concentration of 125I-UdR in medium(r =0.984~0.999). The amount of 125I-UdR in cells and caryons keep increasing with the duration of 125I-UdR co-incubated with Bax-Pc (r=0.867-0.978) . The cell surviving fraction of 125I-UdR groups was significantly lower than that of Na125I groups (.P<0.01) ,and its downward trends were observed with the escalation of the radioactive concentration of 125I-UdR in medium and the extension of co-incubation time. (2) Intratumourally injected 125I-UdR was retained within the tumour tissue without serious leakage. 125I-UdR can damage cancerous cell and distinctly extend the survival of tumour-bearing mice. The changes of hemogram and biochemistry indexes were not observed, but the proliferation of marrow cells were suppressed within a short period (30d) after intratumoral injection of 125I-UdR.Conclusion: 125I-UdR can be incorporated into DNA of Bax-Pc cells, retained within the tumour tissue without serious leakage and kill the cells. The uptake of I25I-UdR is dose dependent and time dependent 125I-UdR can distinctly extend the survival of tumour-bearing mice. Despite the short period suppression of marrow cells, 125I-UdR haswildely value and prospect in clinical application. |
PDF Full Text Request