RADIOPHARMACEUTICALS BASED ON ((R)-1-((6-HYDRAZINYLNICOTINOYL)-D-ALANYL)PYRROLIDIN-2-YL)BORONIC ACID (HYNIC-IFAP) FOR DETECTING THE OVEREXPRESSION OF FIBROBLAST ACTIVATION PROTEIN

The invention relates to new radiopharmaceuticals that inhibit fibroblast activation protein (iFAP), which are based on the molecule ((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl)pyrrolidin-2-yl)boronic acid (HYNIC-iFAP), wherein the nitrogens of the hydrazine of HYNIC act as chemical groups that promot...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Hauptverfasser:	LUNA-GUTIÉRREZ, Myrna Alejandra, JIMÉNEZ-MANCILLA, Nallely Patricia, OCAMPO-GARCÍA, Blanca Elí, SANTOS-CUEVAS, Clara Leticia, FERRO-FLORES, Guillermina, AZORIN-VEGA, Erika Patricia
Format:	Patent
Sprache:	eng ; fre ; spa
Schlagworte:	ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM CHEMISTRY HETEROCYCLIC COMPOUNDS HUMAN NECESSITIES HYGIENE INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES MEASURING MEDICAL OR VETERINARY SCIENCE METALLURGY ORGANIC CHEMISTRY PHYSICS PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS TESTING
Online-Zugang:	Volltext bestellen
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	The invention relates to new radiopharmaceuticals that inhibit fibroblast activation protein (iFAP), which are based on the molecule ((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl)pyrrolidin-2-yl)boronic acid (HYNIC-iFAP), wherein the nitrogens of the hydrazine of HYNIC act as chemical groups that promote the interaction of the HYNIC-iFAP molecule with phenylalanine (Phe-350 and Phe-351), glutamic acid (Glu-203 and Glu-204) and serine (Ser-624) in the active centre of fibroblast activation protein (FAP), combining the conventional use of HYNIC as a chelating agent for the radiometal 99mTc, wherein ethylenediamine diacetic acid (EDDA) is used to complete the radiometal coordination sphere. The new 99mTc-EDDA/HYNIC-iFAP radiopharmaceutical (99mTc-HYNIC-iFAP) detects FAP expressed in the microenvironment of malignant epithelial tumours, with high in-vivo affinity, by means of SPECT molecular imaging techniques in nuclear medicine. The purpose of the invention is to provide a new specific SPECT radiopharmaceutical with high sensitivity for the detection of FAP protein expression in the tumour microenvironment, which is based on boroPro-type inhibitors (molecular-target radiopharmaceuticals). Esta invención se refiere a nuevos radiofármacos inhibidores de la proteína de activación de fibroblastos (iFAP) basados en la molécula ácido ((R)-1-((6-hidrazinilnicotinoil)-D-alanil)pirrolidin-2-il)borónico (HYNIC-iFAP), donde los nitrógenos de la hidracina del HYNIC actúan como grupos químicos favorables para la interacción de la molécula HYNIC-iFAP con la fenilalanina (Phe-350 y Phe-351), el ácido glutámico (Glu-203 y Glu-204) y con la serina (Ser-624) en el centro activo de la proteína de activación de fibroblastos (FAP), aunado al uso convencional del HYNIC como un agente quelante para el radiometal 99mTc, donde el ácido etilendiaminodiacético (EDDA) es usado para completar la esfera de coordinación del radiometal. El nuevo radiofármaco de 99mTc-EDDA/HYNIC-iFAP (99mTc-HYNIC-iFAP) detecta, con alta afinidad in vivo, a la FAP expresada en el microambiente de tumores malignos de origen epitelial mediante técnicas de imagen molecular SPECT en medicina nuclear. El objeto de esta invención es proporcionar un nuevo radiofármaco específico de SPECT con alta sensibilidad para la detección de la expresión de la proteína FAP en el microambiente tumoral, basado en inhibidores tipo boroPro (radiofármaco de blancos moleculares). L'invention concerne de nouveaux radiopharmaceutiques inh