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 ¹¹¹Indium and ¹⁷⁷Lutetium 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 ¹¹¹In and ¹⁷⁷Lu‐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.