ABSTRACT
Objective (1) To evaluate the effect of insertion of two 15-amino-4,7,10,13-tetraoxapentadecanoic (2 PEG4 ) linkers into cyclic Arg-Gly-Asp (RGD) Dimer E [c(RGDfK)]2 on receptor binding in vitro, (2) to assess its biodistribution in vivo and (3) to investigate the value of 99Tcm labeled 2PEG4-Dimer for integrin αvβ3-positive tumors imaging.Methods The expression of U87 human glioma cells and integrin αv β3 was determined by immunofluorescence staining.The half-inhibition concentrations (IC50) for 125 I-cyclo (Arg-Gly-Asp-D-Tyr-Lys) (c(RGDyK) ) of c ( RGDyK ), hydrazinonictinamide ( HYNIC )-Dimer and HYNIC-2PEG4-Dimer binding to integrin αvβ3 were measured.99Tcm-HYNIC-Dimer and 99Tcm-HYNIC-2PEG4-Dimer were synthesized using non-SnCl2 formulation.Biodistribution and imaging studies were performed in nude mice bearing human glioma xenografts.The unpaired t test was used for statistical analysis.Results The labeling yield of the two radiotracers was more than 95%, and the radiochemical purity was more than 99% through Sep-Pek C18 cartridge.HYNIC-2PEG4-Dimer had significantly higher binding affinity of integrin αvβ3 than c(RGDyK) and HYNIC-Dimer (IC50 = 0.8 nmol/L, 27 nmol/L and 2.4 nmol/L, respectively).Biodistribution study showed that 99Tcm-HYNIC-2PEG4-Dimer was mainly excreted via the kidney.The tumor uptake of 99Tcm-HYNIC-2PEG4-Dimer was higher than that of 99Tcm-HYNIC-Dimer at 2h post injection ((5.71 ±0.96) and (2.10 ±0.50) % ID/g, t =4.80, P＜0.05).The xenografted tumors were visible at 0.5 h post injection and the image contrast increased with time due to the tracer clearance of the background tissue.Conclusion 99 Tcm-HYNIC-2PEG4-Dimer is a promising radiotracer for integrin αvβ3-positive tumor imaging.
ABSTRACT
Objective To investigate endometrium receptivity in patients with luteinized unruptured follicle(IUF)by measuring the expression of estrogen receptor(ER),progesterone receptor(PR)and integrin αVβ3 in the endometriunm Methods From May 2007 to Nov.2007,17 infertile women with LUF were selected as LUF group matched with 13 infertile cases with normal ovulation as control group.They all underwent frozen-thawed embryo transfer in Reproductive Medicine Center.Renmin Hospital of Wuhan University.Endometrial tissue in anterior and posterior wall of uterus of LUF group and control group were biopsied by a small curettage between 7 and 11 days after luteinizing hormone(LH)surge.The expression of ER,PR and integrin αVβ3 in endometriam were detected by immunohistochemistry staining.The level of estrogen and progesterone were measured by chemiluminescence assay.Then,the relationship between αVβ3 expression in endometrium and the level of estrogen/progesterone were analyzed in LUF patients.Results (1)There was no remarkable difference in the level of estrogen between LUF [(656±299)pmol/L]and control group[(727±275)pmol/L,P>0.05].However,the level of progesterone were(23±8)nmol/Lin LUF group and(35±10)nmol/L in control group,which reached statistical difference(P<0.01).(2) The expression of ER,PR in endometrium of LUF patients were 183.9±2.4 and 168±3.which were significantly higher than 109.4±6.3 and 106±4 in control group(P<0.01).The expression of integrin α Vβ3 in endometrium of 115±11 in LUF group were significantly lower than 191±9 in control group(P< 0.01).(4)In LUF group,the expression of αVβ3 in endometrium waft correlated positively with the level of progesterone(r=0.77,P<0.01)and irrelevant with the level of estrogen(r=0.01,P>0.05).Conclusion The higher expression of estrogen and progesterone and lower expression of integrin αVβ3 misht confer impaired receptivity of endometrium and interfere with embryo implantation.