Al[18F]F-complexation of DFH17, a NOTA-conjugated adrenomedullin analog, for PET imaging of pulmonary circulation

Abstract

IntroductionAdrenomedullin receptors are highly expressed in human alveolar capillaries and provide a molecular target for imaging the integrity of pulmonary microcirculation. In this work, we aimed to develop a NOTA-derivatized adrenomedullin analog (DFH17), radiolabeled with [18F]AlF, for PET imaging of pulmonary microcirculation. MethodsHighly concentrated [18F](AlF)2+ (15 μL) was produced from purified fluorine-18 in NaCl 0.9%. Various complexation experiments were carried out at Al-to-NOTA molar ratios ranging from 1:1 to 1:40 to assess optimal radiolabeling conditions before using the peptide. DFH17 peptide (2 mM, pH 4) was radiolabeled with [18F](AlF)2+ for 15 min at 100 °C in a total volume of 60 μL. As part of the radiolabeling process, parameters such as fluorine-18 activity (~37 and 1480 MBq), concentration of AlCl3 (0.75, 2, 3, 6 or 10 mM) and the effects of hydrophilic organic solvent (aqueous vs ethanol 50%) were studied. The final formulation was tested for purity, identity and stability in saline. Initial in vivo evaluation of [18F]AlF-DFH17 was performed in normal rats by PET/CT. ResultsThe scaled-up production of [18F]AlF-DFH17 was performed in high radiochemical and chemical purities in an overall radiochemical yield of 22–38% (at end-of-synthesis) within 60 min. The final formulation was stable in saline at different radioactive concentrations for 8 h. PET evaluation in rats revealed high lung-to-background ratios and no defluorination in vivo up to 1 h post-injection. ConclusionThe novel radioconjugate [18F]AlF-DFH17 appears to be a promising PET ligand for pulmonary microcirculation imaging.