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

Martinez, Luis Michel Alonso; Harel, François; Nguyen, Quang T; Létourneau, Myriam; D'Oliviera-Sousa, Caroline; Meloche, Bernard; Finnerty, Vincent; Fournier, Alain; Dupuis, Jocelyn; DaSilva, Jean N. (2018). Al[18F]F-complexation of DFH17, a NOTA-conjugated adrenomedullin analog, for PET imaging of pulmonary circulation Nuclear Medicine and Biology , vol. 67 . p. 36-42. DOI: 10.1016/j.nucmedbio.2018.10.003.

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Résumé

INTRODUCTION: Adrenomedullin 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.

METHODS: Highly 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.

RESULTS: The 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.

CONCLUSION: The novel radioconjugate [18F]AlF-DFH17 appears to be a promising PET ligand for pulmonary microcirculation imaging.

Type de document: Article
Mots-clés libres: Adrenomedullin receptors; Concentrated [(18)F]AlF; NOTA complex
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 20 nov. 2019 15:36
Dernière modification: 20 nov. 2019 15:38
URI: http://espace.inrs.ca/id/eprint/8147

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