Affinity of (nat/68)Ga-Labelled Curcumin and Curcuminoid Complexes for β-Amyloid Plaques: Towards the Development of New Metal-Curcumin Based Radiotracers.
Curcumin derivatives labelled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer's disease. Nevertheless, no study by exploiting the labelling with gallium-68 has been performed so far, in spite of its suitable properties (positron emitter, generator produced radionuclide). Herein, an evaluation of the affinity for synthetic β-amyloid fibrils and for amyloid plaques of three (nat/68)Ga-labelled curcumin analogues, namely curcumin curcumin (CUR), bis-dehydroxy-curcumin (bDHC) and diacetyl-curcumin (DAC), was performed. Affinity and specificity were tested in vitro on amyloid synthetic fibrils by using gallium-68 labelled compounds. Post-mortem brain cryosections from Tg2576 mice were used for the ex vivo visualization of amyloid plaques. The affinity of (68)Ga(CUR)₂⁺, (68)Ga(DAC)₂⁺, and (68)Ga(bDHC)₂⁺ for synthetic β-amyloid fibrils was moderate and their uptake could be observed in vitro. On the other hand, amyloid plaques could not be visualized on brain sections of Tg2576 mice after injection, probably due to the low stability of the complexes in vivo and of a hampered passage through the blood-brain barrier. Like curcumin, all (nat/68)Ga-curcuminoid complexes maintain a high affinity for β-amyloid plaques. However, structural modifications are still needed to improve their applicability as radiotracers in vivo.
Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Arcispedale Santa Maria Nuova-IRCCS, 42123 Reggio Emilia, Italy. rubagotti.sara@asmn.re.it.
Sara
S
Rubagotti
Clinical Immunology, Allergy, and Advanced Biotechnologies Unit, Diagnostic Imaging and Laboratory Medicine Department, IRCCS-Arcispedale Santa Maria Nuova, 42123 Reggio Emilia, Italy. croci.stefania@asmn.re.it.
Stefania
S
Croci
Department of Chemical and Geological Sciences, University of Modena, 41125 Modena, Italy. erika.ferrari@unimore.it.
Erika
E
Ferrari
Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Arcispedale Santa Maria Nuova-IRCCS, 42123 Reggio Emilia, Italy. iori.michele@asmn.re.it.
Michele
M
Iori
Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Arcispedale Santa Maria Nuova-IRCCS, 42123 Reggio Emilia, Italy. capponi.piercesare@asmn.re.it.
Pier C
PC
Capponi
Health Sciences and Technologies-Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40126 Ozzano Emilia, Italy. luca.lorenzini8@unibo.it.
Luca
L
Lorenzini
Health Sciences and Technologies-Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40126 Ozzano Emilia, Italy. laura.calza@unibo.it.
Laura
L
Calzà
Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Arcispedale Santa Maria Nuova-IRCCS, 42123 Reggio Emilia, Italy. versari.annibale@asmn.re.it.
Annibale
A
Versari
Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Arcispedale Santa Maria Nuova-IRCCS, 42123 Reggio Emilia, Italy. asti.mattia@asmn.re.it.
Mattia
M
Asti
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D003474:Curcumin / Q000737:chemistry*; D005710:Gallium Radioisotopes / Q000737:chemistry*; D051379:Mice; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals; D003474:Curcumin
Gallium-68; alzheimer disease; curcumin; curcuminoid complexes; fluorescence; β-amyloid