⁶⁸Ga- and ¹¹¹In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression

αvβ3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [¹⁸F]Galacto-RGD that monitoring of αvβ3 expression is feasible. Here, we introduce ⁶⁸Ga- and ¹¹¹In-labelled derivatives and compare them with [¹⁸F]Galacto-RGD.

For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, αvβ3 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 (αvβ3 positive) and M21-L (αvβ3 negative) cells were used.

Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [⁶⁸Ga]DOTA-RGD and only up to 1.4% for [¹¹¹In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in αvβ3-positive tumours was 2.9 ± 0.3%ID/g and in αvβ3-negative tumours 0.8 ± 0.1%ID/g for [⁶⁸Ga]DOTA-RGD ([¹¹¹In]DOTA-RGD: 1.9 ± 0.3%ID/g and 0.5 ± 0.2%ID/g; [¹⁸F]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 [⁶⁸Ga]DOTA-RGD, tumour/blood ratios were higher for [¹¹¹In]DOTA-RGD and [¹⁸F]Galacto-RGD. However, microPET studies demonstrated that visualisation of αvβ3-positive tumours using [⁶⁸Ga]DOTA-RGD is possible.

Our data indicate that [⁶⁸Ga]DOTA-RGD allows monitoring of αvβ3 expression. Especially, the much easier radiosynthesis compared to [¹⁸F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [¹⁸F]Galacto-RGD remains superior for imaging αvβ3 expression. Introduction of alternative chelator systems may overcome the disadvantages.