title: Dual-isotope 111In/177Lu SPECT imaging as a tool in molecular imaging tracer design.
abstract: 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.
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Hijnen
authors.forename: Anke
authors.initials: A
authors.lastname: de Vries
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
authors.forename: Holger
authors.initials: H
authors.lastname: Grüll
mesh_terms: D000818:Animals; D007205:Indium Radioisotopes; D008187:Lutetium; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000000981:diagnostic imaging; D019047:Phantoms, Imaging; D011849:Radioactive Tracers; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D007205:Indium Radioisotopes; D011849:Radioactive Tracers; D008187:Lutetium