The aluminium-[18F]fluoride revolution: simple radiochemistry with a big impact for radiolabelled biomolecules

Abstract

The aluminium-[18F]fluoride ([18F]AlF) radiolabelling method combines the favourable decay characteristics of fluorine-18 with the convenience and familiarity of metal-based radiochemistry and has been used to parallel gallium-68 radiopharmaceutical developments. As such, the [18F]AlF method is popular and widely implemented in the development of radiopharmaceuticals for the clinic. In this review, we capture the current status of [18F]AlF-based technology and reflect upon its impact on nuclear medicine, as well as offering our perspective on what the future holds for this unique radiolabelling method.

A mass spectrometry-based method for the determination ofin vivobiodistribution of tumor targeting small molecule-metal conjugates

“…Among the three species present, the most abundant one corresponds to Al-OncoFAP-NODAGA. This observation is not unexpected since it is known that NODAGA N 3 O 3 configuration is not favorable for AlF 3 chelation 18,19 . By observing the structures of NODAGA and NOTA chelators, it is possible to note the presence of an extra carboxylic group in the NODAGA structures that saturates Aluminum coordination sphere 18,22 , resulting in the loss of the Fluoride anion (Figure S1).…”

“…Fluorine-18 can be covalently bound to tumor targeting agents (i.e., [ 18 F]-Fluorodeoxyglucose) 20 or indirectly incorporated as counter-ion in Aluminum complexes 19 . Among several metal chelators commercially available for chelating Aluminum Fluoride, the most widely used are NODAGA and NOTA 19,21,22 . For this purpose, OncoFAP-NODAGA and OncoFAP-NOTA were synthetized and labeled with [ nat F]AlF 3 .…”

“…Besides Gallium-68 and Lutetium-177, Fluorine-18 is also frequently used for nuclear medicine applications in cancer patients 17–19 . Fluorine-18 can be covalently bound to tumor targeting agents (i.e., [ 18 F]-Fluorodeoxyglucose) 20 or indirectly incorporated as counter-ion in Aluminum complexes 19 .…”

“…Besides Gallium-68 and Lutetium-177, Fluorine-18 is also frequently used for nuclear medicine applications in cancer patients [17][18][19] . Fluorine-18 can be covalently bound to tumor targeting agents (i.e., [ 18 F]-Fluorodeoxyglucose) 20 or indirectly incorporated as counter-ion in Aluminum complexes 19 . Among several metal chelators commercially available for chelating Aluminum Fluoride, the most widely used are NODAGA and NOTA 19,21,22 .…”

Radiosynthesis and first preclinical evaluation of the novel 11C-labelled FAP inhibitor 11C-FAPI: A comparative study of 11C-FAPIs and [68Ga]Ga-DOTAFAPI-04 in a high–FAP-expression mouse model.

“…The a nities of the inhibitors to FAP did not change considerably upon coupling of these BCAs. Labelled with the positron emitter radionuclide 68 Ga, 18 F-Al, or 64 Cu complex, these tracers demonstrated high tumour-tonoise contrast ratios, fast elimination, and the successful imaging of tumour metastases [8][9][10][11][12] . In addition, the BCA-coupled compounds can be labelled with therapeutic nuclides, such as 90 Y [13,14] , 153 Sm [15] , 177 Lu [16][17][18] , 211 At [19] , and 225 Ac [20] , for tumour treatment.…”