{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:44:08Z","timestamp":1790721848502,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Compagnia di San Paolo"},{"name":"LiFTT"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Al(III) complexes have been recently investigated for their potential use in imaging with positron emission tomography (PET) by formation of ternary complexes with the radioisotope fluorine-18 (18F). Although the derivatives of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) are the most applied chelators for [Al18F]2+ labelling and (pre)clinical PET imaging, non-macrocyclic, semi-rigid pentadentate chelators having two N- and three O-donor atoms such as RESCA1 and AMPDA-HB have been proposed with the aim to allow room temperature labelling of temperature-sensitive biomolecules. The paucity of stability data on Al(III) complexes used for PET imaging instigated a complete thermodynamic and kinetic solution study on Al(III) complexes with aminomethylpiperidine (AMP) derivatives AMPTA and AMPDA-HB and the comparison with a RESCA1-like chelator CD3A-Bn (trans-1,2-diaminocyclohexane-N-benzyl-N,N\u2032,N\u2032-triacetic acid). The stability constant of [Al(AMPDA-HB)] is about four orders of magnitude higher than that of [Al(AMPTA)] and [Al(CD3A-Bn)], highlighting the greater affinity of phenolates with respect to acetate O-donors. On the other hand, the kinetic inertness of the complexes, determined by following the Cu2+-mediated transmetallation reactions in the 7.5\u201310.5 pH range, resulted in a spontaneous and hydroxide-assisted dissociation slightly faster for [Al(AMPTA)] than for the other two complexes (t1\/2 = 4.5 h for [Al(AMPTA)], 12.4 h for [Al(AMPDA-HB)], and 24.1 h for [Al(CD3A-Bn)] at pH 7.4 and 25 \u00b0C). Finally, the [AlF]2+ ternary complexes were prepared and their stability in reconstituted human serum was determined by 19F NMR experiments.<\/jats:p>","DOI":"10.3390\/molecules28093764","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T02:02:23Z","timestamp":1682647343000},"page":"3764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Thermodynamic and Kinetic Stabilities of Al(III) Complexes with N2O3 Pentadentate Ligands"],"prefix":"10.3390","volume":"28","author":[{"given":"Edoardo","family":"Callegari","sequence":"first","affiliation":[{"name":"Department of Science and Technological Innovation, Universit\u00e0 del Piemonte Orientale, Viale T. Michel 11, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5386-9015","authenticated-orcid":false,"given":"Jonathan","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation, Universit\u00e0 del Piemonte Orientale, Viale T. Michel 11, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol","family":"Guidolin","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging S.p.A., Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Boccalon","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging S.p.A., Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Baranyai","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging S.p.A., Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-8396","authenticated-orcid":false,"given":"Lorenzo","family":"Tei","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation, Universit\u00e0 del Piemonte Orientale, Viale T. Michel 11, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13014-020-01519-1","article-title":"Recent advances of PET imaging in clinical radiation oncology","volume":"15","author":"Unterrainer","year":"2020","journal-title":"Radiat. Oncol."},{"key":"ref_2","first-page":"55","article-title":"Positron emission tomography (PET) imaging with (18)F-based radiotracers","volume":"2","author":"Alauddin","year":"2012","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/s00259-020-04967-9","article-title":"The value of 18F-FDG PET\/CT for predicting or monitoring immunotherapy response in patients with metastatic melanoma: A systematic review and meta-analysis","volume":"48","author":"Ayati","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ccr.2019.04.005","article-title":"Coordination chemistry and applications of medium\/high oxidation state metal and non-metal fluoride and oxide-fluoride complexes with neutral donor ligands","volume":"391","author":"Levason","year":"2019","journal-title":"Coord. Chem. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s41181-021-00141-0","article-title":"The aluminium-[18F]fluoride revolution: Simple radiochemistry with a big impact for radiolabelled biomolecules","volume":"6","author":"Archibald","year":"2021","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"215028","DOI":"10.1016\/j.ccr.2023.215028","article-title":"Radiochemistry with {Al18F}2+: Current status and optimization perspectives for efficient radiofluorination by complexation","volume":"480","author":"Schmitt","year":"2023","journal-title":"Coord. Chem. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fersing, C., Bouhlel, A., Cantelli, C., Garrigue, P., Lisowski, V., and Guillet, B. (2019). A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [18F]fluoride: Will [18F]AlF Replace 68Ga for Metal Chelate Labeling?. Molecules, 24.","DOI":"10.3390\/molecules24162866"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1021\/acs.bioconjchem.7b00817","article-title":"18F-AlF Labeled Peptide and Protein Conjugates as Positron Emission Tomography Imaging Pharmaceuticals","volume":"29","author":"Kumar","year":"2018","journal-title":"Bioconjug. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"991","DOI":"10.2967\/jnumed.108.060418","article-title":"A novel method of 18F radiolabeling for PET","volume":"50","author":"McBride","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/jlcr.3161","article-title":"Al18F labeling of peptides and proteins","volume":"57","author":"Laverman","year":"2014","journal-title":"J. Label. Compd. Rad."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"454","DOI":"10.2967\/jnumed.109.066902","article-title":"A novel facile method of labeling octreotide with 18F-fluorine","volume":"51","author":"Laverman","year":"2010","journal-title":"J. Nucl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"691","DOI":"10.2967\/jnumed.112.113563","article-title":"First Experience of 18F-Alfatide in Lung Cancer Patients Using a New Lyophilized Kit for Rapid Radiofluorination","volume":"54","author":"Wan","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/RLU.0000000000002578","article-title":"Clinical application of 18F-AlF-NOTA-octreotide PET\/CT in combination with 18F-FDG PET\/CT for imaging neuroendocrine neoplasms","volume":"44","author":"Long","year":"2019","journal-title":"Clin. Nucl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1021\/acs.molpharmaceut.8b00192","article-title":"Development of [18 F]AlF-NOTA-NT as PET agents of neurotensin receptor-1 positive pancreatic cancer","volume":"15","author":"Wang","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1021\/acs.bioconjchem.6b00012","article-title":"New chelators for low temperature Al18F-labeling of biomolecules","volume":"27","author":"Cleeren","year":"2016","journal-title":"Bioconjug. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.7150\/thno.20094","article-title":"Al18F-labeling of heat-sensitive biomolecules for positron emission tomography imaging","volume":"7","author":"Cleeren","year":"2017","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1038\/s41596-018-0040-7","article-title":"Direct fluorine-18 labeling of heat-sensitive biomolecules for positron emission tomography imaging using the Al18F-RESCA method","volume":"13","author":"Cleeren","year":"2018","journal-title":"Nat. Prot."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.2967\/jnumed.119.238782","article-title":"Development and evaluation of interleukin-2\u2013derived radiotracers for PET imaging of T cells in mice","volume":"61","author":"Suurs","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/cmdc.201900652","article-title":"Room temperature Al18F labeling of 2-aminomethylpiperidine-based chelators for PET imaging","volume":"15","author":"Russelli","year":"2020","journal-title":"ChemMedChem"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11144-015-0892-6","article-title":"Equilibrium and dissociation kinetics of the [Al(NOTA)] complex (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetate)","volume":"116","author":"Farkas","year":"2015","journal-title":"React. Kinet. Mech. Catal."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Martinelli, J., Callegari, E., Baranyai, Z., Fraccarollo, A., Cossi, M., and Tei, L. (2021). Semi-Rigid (Aminomethyl) Piperidine-Based Pentadentate Ligands for Mn(II) Complexation. Molecules, 26.","DOI":"10.3390\/molecules26195993"},{"key":"ref_22","unstructured":"Musthakahmed, A.M.S., Billaud, E., Bormans, G., Cleeren, F., Lecina, J., and Verbruggen, A. (2018). Methods for Low Temperature Fluorine-18 Radiolabeling of Biomolecules. (US20180273441A1)."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1021\/ic00265a012","article-title":"New-dimensional cyclam. Synthesis, crystal structure, and chemical properties of macrocyclic tetraamines bearing a phenol pendant","volume":"26","author":"Kimura","year":"1987","journal-title":"Inorg. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1021\/ac60305a041","article-title":"Polarimetric studies of alkali metal ion complexes of 1-trans-1,2-diaminocyclohexane-N,N,N\u2032,N\u2032-tetraacetic acid","volume":"43","author":"Carr","year":"1971","journal-title":"Anal. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1021\/ja00792a018","article-title":"Alkali metal ion complexes of 2,3-diaminobutane-N,N,N\u2032N\u2032-tetraacetic acid","volume":"95","author":"Carr","year":"1973","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11138","DOI":"10.1039\/D1SC02200H","article-title":"Defining the conditions for the development of the emerging class of FeIII-based MRI contrast agents","volume":"12","author":"Baranyai","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1021\/ac60250a020","article-title":"Potentiometric characterization of aluminum aminopolycarboxylate chelonates","volume":"39","author":"Aikens","year":"1967","journal-title":"Anal. Chem."},{"key":"ref_28","unstructured":"Baes, C.F., and Mesmer, R.E. (1976). The Hydrolysis of Cations, Wiley."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/S0277-5387(00)84637-9","article-title":"Equilibrium study of the systems of aluminium(III), gallium(III) and indium(III) with mercaptoacetate, 3-mercaptopropionate and 2-mercaptobenzoate","volume":"3","author":"Toth","year":"1984","journal-title":"Polyhedron"},{"key":"ref_30","first-page":"59","article-title":"X-ray structural analysis of biologically relevant aluminium(III) complexes","volume":"149","author":"Powell","year":"1996","journal-title":"Coord. Chem. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/mrc.1260270406","article-title":"Complexes of aluminium with aminopolycarboxylic acids: 27Al NMR and potentiometric studies","volume":"27","author":"Iyer","year":"1989","journal-title":"Magn. Res. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/mrc.1260270414","article-title":"71Ga nuclear magnetic resonance investigation of aqueous gallium(III) and its hydrolysis","volume":"27","author":"Akitt","year":"1989","journal-title":"Magn. Res. Chem."},{"key":"ref_33","first-page":"347","article-title":"Binding and transport of aluminum by serum proteins","volume":"149","author":"Harris","year":"1996","journal-title":"Coord. Chem. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0003-2670(01)80616-4","article-title":"A study of some problems in determining the stoicheiometric proton dissociation constants of complexes by potentiometric titrations using a glass electrode","volume":"38","author":"Irving","year":"1967","journal-title":"Anal. Chim. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Legett, D.J. (1985). Computational Method for Determination of Formation Constants, Plenum Press.","DOI":"10.1007\/978-1-4684-4934-1_1"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/9\/3764\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:24:35Z","timestamp":1760124275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/9\/3764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,27]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["molecules28093764"],"URL":"https:\/\/doi.org\/10.3390\/molecules28093764","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,27]]}}}