Morrison Matthew S, Ricketts Sally-Ann, Barnett Jon, Cuthbertson Alan, Tessier Jean, Wedge Stephen R
GE Healthcare MDx Research, The Grove Centre, Amersham, United Kingdom.
J Nucl Med. 2009 Jan;50(1):116-22. doi: 10.2967/jnumed.108.056077. Epub 2008 Dec 17.
Despite the recent development of various radiolabeled Arg-Gly-Asp (RGD) peptides for imaging the alphavbeta3 integrin receptor, relatively little attention has been focused on the ability of these radiotracers to monitor changes in tumor vascularity after antitumor therapies. This study describes the favorable in vivo kinetics and tumor-targeting properties of 18F-AH111585, a novel 18F-RGD peptide, and its ability to monitor tumor vascularity noninvasively.
Mice bearing Lewis lung carcinoma (LLC) tumors or Calu-6 non-small cell lung tumor xenografts were used for in vivo biodistribution and small-animal PET imaging studies. In addition, some animals were treated with either low-dose paclitaxel or the vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor ZD4190. Tumor uptake of 18F-AH111585 and microvessel density were then assessed.
Biodistribution of 18F-AH111585 demonstrated rapid clearance from the blood and key background organs and good tumor accumulation, with 1.5 percentage injected dose per gram (%ID/g) present at 2 h after injection in LLC tumors. Small-animal PET imaging of Calu-6 tumors allowed visualization of tumors above background tissue, with mean baseline uptake of 2.2 %ID/g. Paclitaxel therapy reduced the microvessel density in LLC tumor-bearing mice and resulted in significantly reduced 18F-AH111585 tumor uptake (P<0.05). ZD4190 therapy resulted in a significant (31.8%) decrease in 18F-AH111585 uptake in Calu-6 tumors, compared with the vehicle control-treated Calu-6 tumors, which had a 26.9% increase in 18F-AH111585 uptake over the same period (P<0.01).
18F-AH111585 is a promising 18F-labeled RGD tracer that offers a new approach to noninvasively image tumor vasculature. This tracer may reveal important information in the assessment of the impact of antitumor therapies, in particular those that predominantly target tumor blood vessels.
尽管最近开发了各种用于成像αvβ3整合素受体的放射性标记的精氨酸 - 甘氨酸 - 天冬氨酸（RGD）肽，但相对较少关注这些放射性示踪剂监测抗肿瘤治疗后肿瘤血管变化的能力。本研究描述了新型18F - RGD肽18F - AH111585良好的体内动力学和肿瘤靶向特性及其无创监测肿瘤血管的能力。
携带Lewis肺癌（LLC）肿瘤或Calu - 6非小细胞肺癌异种移植瘤的小鼠用于体内生物分布和小动物PET成像研究。此外，一些动物接受低剂量紫杉醇或血管内皮生长因子受体 - 2酪氨酸激酶抑制剂ZD4190治疗。然后评估18F - AH111585的肿瘤摄取和微血管密度。
１８Ｆ－ＡＨ１１１５８５的生物分布显示其能从血液和关键背景器官快速清除，并具有良好的肿瘤蓄积，在LLC肿瘤中注射后2小时每克有1.5％注射剂量（％ID/g）。Calu - 6肿瘤的小动物PET成像可使肿瘤在背景组织之上显影，平均基线摄取为2.2％ID/g。紫杉醇治疗降低了携带LLC肿瘤小鼠的微血管密度，并导致18F - AH111585肿瘤摄取显著降低（P<0.05）。与载体对照治疗的Calu - 6肿瘤相比，ZD4190治疗导致Calu - 6肿瘤中18F - AH111585摄取显著降低（31.8％），而载体对照治疗的Calu - 6肿瘤在同一时期18F - AH111585摄取增加了26.9％（P<0.01）。
18F - AH111585是一种有前景的18F标记的RGD示踪剂，为无创成像肿瘤血管提供了一种新方法。这种示踪剂可能在评估抗肿瘤治疗的影响，特别是那些主要靶向肿瘤血管的治疗的影响方面揭示重要信息。
