Decristoforo Clemens, Hernandez Gonzalez Ignacio, Carlsen Janette, Rupprich Marco, Huisman Marc, Virgolini Irene, Wester Hans-Jürgen, Haubner Roland
Department of Nuclear Medicine, Medizinische Universität Innsbruck, Innsbruck, Austria.
Eur J Nucl Med Mol Imaging. 2008 Aug;35(8):1507-15. doi: 10.1007/s00259-008-0757-6. Epub 2008 Mar 28.
PURPOSE: alphavbeta3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [(18)F]Galacto-RGD that monitoring of alphavbeta3 expression is feasible. Here, we introduce (68)Ga- and (111)In-labelled derivatives and compare them with [(18)F]Galacto-RGD. METHODS: For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, alphavbeta3 affinity and cell uptake and for in vivo characterization, biodistribution studies and micro positron emission tomography (PET) imaging were carried out. For in vivo and in vitro studies, human melanoma M21 (alphavbeta3 positive) and M21-L (alphavbeta3 negative) cells were used. RESULTS: Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [(68)Ga]DOTA-RGD and only up to 1.4% for [(111)In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in alphavbeta3-positive tumours was 2.9 +/- 0.3%ID/g and in alphavbeta3-negative tumours 0.8 +/- 0.1%ID/g for [(68)Ga]DOTA-RGD ([(111)In]DOTA-RGD: 1.9 +/- 0.3%ID/g and 0.5 +/- 0.2%ID/g; [(18)F]Galacto-RGD: 1.6 +/- 0.2%ID/g and 0.4 +/- 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [(68)Ga]DOTA-RGD, tumour/blood ratios were higher for [(111)In]DOTA-RGD and [(18)F]Galacto-RGD. However, microPET studies demonstrated that visualisation of alphavbeta3-positive tumours using [(68)Ga]DOTA-RGD is possible. CONCLUSIONS: Our data indicate that [(68)Ga]DOTA-RGD allows monitoring of alphavbeta3 expression. Especially, the much easier radiosynthesis compared to [(18)F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [(18)F]Galacto-RGD remains superior for imaging alphavbeta3 expression. Introduction of alternative chelator systems may overcome the disadvantages.
目的：αvβ3整合素是参与血管生成过程的重要细胞黏附受体。最近，我们利用[¹⁸F]半乳糖-RGD证明监测αvβ3表达是可行的。在此，我们引入了⁶⁸Ga和¹¹¹In标记的衍生物，并将它们与[¹⁸F]半乳糖-RGD进行比较。 方法：为进行放射性标记，使用固相多肽合成法合成了环（RGDfK（DOTA））。为进行体外特性表征，测定分配系数、蛋白质结合、代谢稳定性、αvβ3亲和力和细胞摄取；为进行体内特性表征，开展了生物分布研究和微型正电子发射断层扫描（PET）成像。体内和体外研究均使用人黑色素瘤M21（αvβ3阳性）和M21-L（αvβ3阴性）细胞。 结果：两种示踪剂均可直接合成。这些化合物具有亲水性且代谢稳定性高。发现[⁶⁸Ga]DOTA-RGD的蛋白结合活性高达23%，而[¹¹¹In]DOTA-RGD仅高达1.4%。细胞摄取研究表明存在受体特异性聚集。生物分布数据证实了这一点。注射后1小时，[⁶⁸Ga]DOTA-RGD在αvβ3阳性肿瘤中的聚集量为2.9±0.3%ID/g，在αvβ3阴性肿瘤中为0.8±0.1%ID/g（[¹¹¹In]DOTA-RGD：1.9±0.3%ID/g和0.5±0.2%ID/g；[¹⁸F]半乳糖-RGD：1.6±0.2%ID/g和0.4±0.1%ID/g）。因此，肿瘤摄取率相当。由于[⁶⁸Ga]DOTA-RGD的血池活性约高3倍，[¹¹¹In]DOTA-RGD和[¹⁸F]半乳糖-RGD的肿瘤/血比值更高。然而，微型PET研究表明使用[⁶⁸Ga]DOTA-RGD可视化αvβ3阳性肿瘤是可行的。 结论：我们的数据表明[⁶⁸Ga]DOTA-RGD可用于监测αvβ3表达。特别是与[¹⁸F]半乳糖-RGD相比，其放射性合成要容易得多，这将使其成为一个有吸引力的替代选择。然而，由于血池活性较高，[¹⁸F]半乳糖-RGD在成像αvβ3表达方面仍更具优势。引入替代螯合剂系统可能会克服这些缺点。
Eur J Nucl Med Mol Imaging. 2008-8
Eur J Nucl Med Mol Imaging. 2011-4-13
Eur J Nucl Med Mol Imaging. 2007-12
Nucl Med Biol. 2015-2
Nucl Med Biol. 2006-11
RMD Open. 2024-2-9
Eur J Nucl Med Mol Imaging. 2023-9
Nucl Med Commun. 2007-11
J Nucl Med. 2007-9
Q J Nucl Med Mol Imaging. 2007-3
Eur J Nucl Med Mol Imaging. 2006-7
Nature. 2005-12-15
Eur J Nucl Med Mol Imaging. 2005-4
Zotero 插件