super(68)Ga- and super(111)In-labelled DOTA-RGD peptides for imaging of alpha v beta 3 integrin expression

• Published in: European Journal of Nuclear Medicine Vol. 35; no. 8; pp. 1507 - 1515
• Main Authors: Decristoforo, Clemens, Hernandez Gonzalez, Ignacio, Carlsen, Janette, Rupprich, Marco, Huisman, Marc, Virgolini, Irene, Wester, Hans-Juergen, Haubner, Roland
• Format: Journal Article
• Language: English
• Published: 01-08-2008
• DOI: 10.1007/s00259-008-0757-6
• EISSN: 1619-7089
• ISSN: 0340-6997

Purpose: alpha v beta 3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [ super(18)F]Galacto-RGD that monitoring of alpha v beta 3 expression is feasible. Here, we introduce super(68)Ga- and super(111)In-labelled derivatives and compare them with [ super(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, alpha v beta 3 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 ( alpha v beta 3 positive) and M21-L ( alpha v beta 3 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 [ super(68)Ga]DOTA-RGD and only up to 1.4% for [ super(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 alpha v beta 3-positive tumours was 2.9 plus or minus 0.3%ID/g and in alpha v beta 3-negative tumours 0.8 plus or minus 0.1%ID/g for [ super(68)Ga]DOTA-RGD ([ super(111)In]DOTA-RGD: 1.9 plus or minus 0.3%ID/g and 0.5 plus or minus 0.2%ID/g; [ super(18)F]Galacto-RGD: 1.6 plus or minus 0.2%ID/g and 0.4 plus or minus 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [ super(68)Ga]DOTA-RGD, tumour/blood ratios were higher for [ super(111)In]DOTA-RGD and [ super(18)F]Galacto-RGD. However, microPET studies demonstrated that visualisation of alpha v beta 3-positive tumours using [ super(68)Ga]DOTA-RGD is possible. Conclusions: Our data indicate that [ super(68)Ga]DOTA-RGD allows monitoring of alpha v beta 3 expression. Especially, the much easier radiosynthesis compared to [ super(18)F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [ super(18)F]Galacto-RGD remains superior for imaging alpha v beta 3 expression. Introduction of alternative chelator systems may overcome the disadvantages.