title: A novel injectable formulation of 6-fluoro-l-DOPA imaging agent for diagnosis of neuroendocrine tumors and Parkinson's disease.
abstract: Two [19F]F-l-DOPA (F-DOPA) new β-cyclodextrin (CD)-based dosage forms (FA and FB, respectively) have been studied and their physico-chemical and pharmacological features determined to overcome the administration site reactions showed by the currently used [18F]F-l-DOPA formulation (IASOdopa®) to perform PET-CT diagnosis in oncology (neuroendocrine tumors) and neurological (Parkinson's disease) field. Chemical stability of FA and FB was found to be longer than IASOdopa®by adding the thiol-antioxidant agent, L-Cysteine.1H and19F NMR investigations suggest the formation of an inclusion complex of F-DOPA with β-CD. In vitro experiments on the effects of FA and FB on mouse skeletal muscle fibers and on the human neuroblastoma SH-SY5Y and embryonal kidney tsA201 cell lines viability showed that FA was the most performant formulation compared to F-DOPA solutions. In vivo tolerability tests of FA on adult male rat showed no significant effects on body weight and no change in their dried organs weight. In addition, their metabolic and physiological parameters were not affected. In conclusion, [18F]F-l-DOPA, formulated as FA, constitutes a promising dosage form for PET-CT diagnosis of both neuroendocrine tumors and Parkinson's disease.
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy. Electronic address: adriana.trapani@uniba.it.
authors.forename: Adriana
authors.initials: A
authors.lastname: Trapani
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Tricarico
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Mele
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy.
authors.forename: Fatima
authors.initials: F
authors.lastname: Maqoud
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Mandracchia
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Vitale
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Capriati
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Trapani
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Dimiccoli
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Tolomeo
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco-Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy, Italy. Electronic address: antonio.scilimati@uniba.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Scilimati
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003545:Cysteine / Q000008:administration & dosage; D004295:Dihydroxyphenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009447:Neuroblastoma / Q000175:diagnosis; D018358:Neuroendocrine Tumors / Q000175:diagnosis*; D010300:Parkinson Disease / Q000175:diagnosis*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D047392:beta-Cyclodextrins / Q000008:administration & dosage
chemical_list: D019275:Radiopharmaceuticals; D047392:beta-Cyclodextrins; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D003545:Cysteine
keywords: 2-hydroxypropyl-beta-cyclodextrin (PubMed CID: 44134771); 6-Fluoro-l-dopa (PubMed CID: 107730); Antioxidant agents; Cyclodextrins; F-DOPA; L-Cysteine hydrochloride (PubMed CID: 60960); NMR; Pharmacological assays; beta-Cyclodextrin (PubMed CID: 444041); glutathione (PubMed CID: 124886)