RESUMO
Radio-HPLC is an essential method to assess the purity of PET radiopharmaceuticals. The usual NaI scintillator radiodetector requires heavy, costly and cumbersome lead shielding. The luminescence LB 500 fLumo detector has been developed to tackle these drawbacks and achieve high sensitivity. The fLumo uses a photon counting detector combined with a flow-through cell modified with a solid melt-on scintillator only sensitive to the positron. This study demonstrates the usefulness of the fLumo for analysis and purification of PET radiopharmaceuticals.
Assuntos
Radioisótopos de Flúor/análise , Compostos Radiofarmacêuticos/análise , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção , Medições Luminescentes/instrumentação , Medições Luminescentes/métodos , Tomografia por Emissão de Pósitrons/instrumentação , Tomografia por Emissão de Pósitrons/métodos , Controle de QualidadeRESUMO
Coronary disease risk increases inversely with high-density lipoprotein (HDL) level. The measurement of the biodistribution and clearance of HDL in vivo, however, has posed a technical challenge. This study presents an approach to the development of a lipoprotein MRI agent by linking gadolinium methanethiosulfonate (Gd[MTS-ADO3A]) to a selective cysteine mutation in position 55 of apo AI, the major protein of HDL. The contrast agent targets both liver and kidney, the sites of HDL catabolism, whereas the standard MRI contrast agent, gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (GdDTPA-BMA, gadodiamide), enhances only the kidney image. Using a modified apolipoprotein AI to create an HDL contrast agent provides a new approach to investigate HDL biodistribution, metabolism and regulation in vivo.
Assuntos
Apolipoproteína A-I/metabolismo , Gadolínio/metabolismo , Lipoproteínas HDL/metabolismo , Imageamento por Ressonância Magnética/métodos , Animais , Apolipoproteína A-I/química , Apolipoproteína A-I/genética , Meios de Contraste/química , Meios de Contraste/metabolismo , Doença das Coronárias/metabolismo , Gadolínio/química , Humanos , Rim/anatomia & histologia , Rim/metabolismo , Lipoproteínas HDL/química , Fígado/anatomia & histologia , Fígado/metabolismo , Masculino , Mesilatos/química , Mesilatos/metabolismo , Camundongos , Modelos Moleculares , Estrutura Secundária de ProteínaRESUMO
The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click type reaction was used to label a peptide with fluorine-18. A novel solid phase synthesis approach for the preparation of clickable peptides has been developed and has also permitted the straightforward preparation of reference compounds. A complementary azide labeling agent (1-(azidomethyl)-4-[(18)F]-fluorobenzene) has been produced in a four step procedure in 75 min with a 34% radiochemical yield (decay corrected). Conjugation of [(18)F]fluoroazide with a model alkyne-neuropeptide produced the desired (18)F-radiolabeled peptide in less than 15 min with a yield of 90% and excellent radiochemical purity.