Dual‐isotope 111In/177Lu SPECT imaging as a tool in molecular imaging tracer design

The synthesis, design and subsequent pre-clinical testing of new molecular imaging tracers are topic of extensive research in healthcare. Quantitative dual-isotope SPECT imaging is proposed here as a tool in the design and validation of such tracers, as it can be used to quantify and compare the biodistribution of a specific ligand and its nonspecific control ligand, labeled with two different radionuclides, in the same animal. Since the biodistribution results are not blurred by experimental or physiological inter-animal variations, this approach allows determination of the ligand’s net targeting effect. However, dual-isotope quantification is complicated by crosstalk between the two radionuclides used and the radionuclides should not influence the biodistribution of the tracer. Here, we developed a quantitative dual-isotope SPECT protocol using combined 111 Indium and 177 Lutetium and tested this tool for a well-known angiogenesis-specific ligand (cRGD peptide) in comparison to a potential nonspecific control (cRAD peptide). Dual-isotope SPECT imaging of the peptides showed a similar organ and tumor uptake to single-isotope studies (cRGDfK–DOTA, 1.5 � 0.8%ID cm � 3 ; cRADfK–DOTA, 0.2 � 0.1%ID cm � 3 ), but with higher statistical relevance (p-value 0.007, n=8). This demonstrated that, for the same relevance, seven animals were required in case of a single-isotope test design as compared with only three animals when a dual-isotope test was used. Interchanging radionuclides did not influence the biodistribution of the peptides. Dual-isotope SPECT after simultaneous injection of 111 In and 177 Lu-labeled cRGD and cRAD was shown to be a valuable method for paired testing of the in vivo target specificity of ligands in molecular imaging tracer design. Copyright © 2012 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this paper.