Preliminary study of molecular imaging of human hepatoceilular carcinoma xenoggaft with Gd-based MR probe containiug arginine-glycine-aspartic acid chelate / 中华放射学杂志

ABSTRACT

Objective To develop a Gd-based MR probe containing arginine-glyeine-aspartic acid (RGD)motif to reveal integrin avβ3 receptor-expressed tumor.Methods Commercially available HYNICRGD conjugate with co-ligand EDDA was labeled with GdCl3,and the mixture was isolated and purified by solid phase extract(SPE)to get the entire probe Gd-EDDA-HYNIC-RGD.Human HCC cell line BEL-7402 was cultured and the cells harvested and suspended then subcutaneously inoculated into athymic nude mice for tumor growth.In vitro cell binding assay to integrin avβ3 receptor and cell viability experiments were conducted.Then in vivo,imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at baseline and time points of 0.30,60,90 mninutes and 24 hour post-intravenous injection(P.i.) via the tail vein.Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results.Results Gd-EDDA-HYNIC-RGD was successfully isolated by SPE and validity was verifled on signal enhancement througll in vitro and in vivo experiments.The T1 relaxation rate of the probe is 3.31 mmol/sIt is well tolerated to living cells when the concentration of the probe is below 0.1 μmol/ml;both BEL-7402 Hunlan Hepatocellular Carcinoma cell Iine and the tumor expressed avβ3receptor;The RGD-iigand was observed specificly binding with avβ3 receptor in vitro;The nude mice model bearing HHCC was well estabhshed.The signal intensity(SI)at the tumor site were 2247.6±39.0 at baseline and 2820.9±35.2 at 90 min p.i.respectively,the SI at 90min increased less than 25%of baseline,which is statistically different(t=-38.031,P＜0.05);while the SI at muscle site were 1824.2±32.8 and 1845.8±27.2 respectively,which is not statistically different(t=-1.424,P＞0.05);The signal to time curve for probe-administrated group is straightforward over time in the span of 0 to 90 minute p.i.while the control arms do not show such tendency.Conclusion Gd-EDDA-HYNIC-RGD has the potential to used as an MR probe detecting integrin avβ3 receptor-expressed tumor.This work may offer possibility of early detection and differentiation of specific tumors.