Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Eur J Nucl Med Mol Imaging. 2011 Jan;38(1):128-37. doi: 10.1007/s00259-010-1615-x. Epub 2010 Sep 21.
Due to the restricted expression of α(v)β(3) in tumours, α(v)β(3) is considered a suitable receptor for tumour targeting. In this study the α(v)β(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their (111)In-labelled counterparts.
A monomeric (E-c(RGDfK)), a dimeric (E-c(RGDfK)) and a tetrameric (E{Ec(RGDfK)}(2)) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with (68)Ga. In vitro α(v)β(3)-binding characteristics were determined in a competitive binding assay. In vivo α(v)β(3)-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner.
The IC(50) values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-c(RGDfK) and DOTA-E{Ec(RGDfK)}(2) were 23.9 ± 1.22, 8.99 ± 1.20 and 1.74 ± 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 ± 1.15, 3.34 ± 1.16 and 1.80 ± 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the (68)Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 ± 0.30, 5.24 ± 0.27 and 7.11 ± 0.67%ID/g, respectively) was comparable to that of their (111)In-labelled counterparts (2.70 ± 0.29, 5.61 ± 0.85 and 7.32 ± 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised.
The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The (68)Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of α(v)β(3) expression with PET.
由于 α(v)β(3)在肿瘤中的表达受限，因此 α(v)β(3)被认为是肿瘤靶向的合适受体。在本研究中，测定了（68）Ga 标记的单体、二聚体和四聚体 RGD 肽的 α(v)β(3)结合特性，并将其与相应的（111）In 标记物进行了比较。
合成了单体（E-c（RGDfK））、二聚体（E-[c（RGDfK）]（2））和四聚体（E{E[c（RGDfK）]（2）}（2））RGD 肽，与 DOTA 缀合并与（68）Ga 标记。在竞争结合测定中测定了体外 α(v)β(3)-结合特性。在皮下生长的 SK-RC-52 异种移植瘤小鼠中评估了化合物的体内 α(v)β(3)-靶向特性。此外，使用 microPET/CT 扫描仪获取 microPET 图像。
Ga(III)-标记的 DOTA-E-c（RGDfK）、DOTA-E-[c（RGDfK）]（2）和 DOTA-E{E[c（RGDfK）]（2）}（2）的 IC50 值分别为 23.9 ± 1.22、8.99 ± 1.20 和 1.74 ± 1.18 nM，与相应的 In(III)-标记的单、二聚体和四聚体 RGD 肽（26.6 ± 1.15、3.34 ± 1.16 和 1.80 ± 1.37 nM）相似。在注射后 2 小时，（68）Ga 标记的单、二聚体和四聚体 RGD 肽（3.30 ± 0.30、5.24 ± 0.27 和 7.11 ± 0.67%ID/g）的肿瘤摄取与相应的（111）In 标记物（2.70 ± 0.29、5.61 ± 0.85 和 7.32 ± 2.45%ID/g）相当。PET 扫描与生物分布数据一致。在所有 PET 扫描中，肿瘤均能清晰显示。
整合素亲和力和肿瘤摄取的顺序为 DOTA-四聚体>DOTA-二聚体>DOTA-单体。（68）Ga 标记的四聚体 RGD 肽具有用于 PET 成像 α(v)β(3)表达的优异特性。
