Development of novel peptide based radiopharmaceuticals for in vivo receptor associated tumor diagnosis and therapy

Información del proyecto

Identificador del acuerdo de subvención: BMH4983198

Proyecto cerrado

Fecha de inicio 1 Abril 1998

Fecha de finalización 31 Marzo 2001

Financiado con arreglo a

• Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998

Coste total

Sin datos

Aportación de la UE

Sin datos

Coordinado por

Forschungszentrum Rossendorf e.V.
Germany

Objetivo

Objectives
The major goal of this project is to develop novel neurotensin (NT) and bombesin/gastrin releasing peptide (BBN/GRP) analogs, that can be tagged with radionuclides appropriate for either diagnostic (PET, SPECT) or therapeutic application. The new peptide based radioagents will be evaluated as new molecular probes for the early in vivo diagnosis and/or therapy of NT or BBN/GRP receptor positive tumors and their metastases.

Neuropeptides are a class of very potent native substances controlling important biological processes through high affinity receptors located on the cell membrane of target cells. After the discovery had been made that a wide spectrum of malignant cells also express high affinity and high density peptide receptors on their surface, neuropeptides have been drawing increasing attention in the Nuclear Medicine world. Their superiority over Monoclonal Antibodies (MoAbs) used so far relies upon their unique biological characteristics, most importantly their rapid and specific localization on target cells in combination with their fast blood clearance. It is therefore their pharmacokinetics as well as target specificity that make them attractive vectors for targeting cancer, a strategy already explored successfully forsomatostatin (SS). Indeed, the in vivo imaging of SS receptors involved in much pathology by radiolabeled SS analogs is a new powerful and fast expanding technique. However, since many frequently occurring and devastating tumors do not express SS receptors, it is imperative to search for alternative neuropeptide receptors expressed by these tumors. Recent evidence reports that such malignant lesions, like small cell lung cancer (SCLC), colon carcinoma and certain meningiomas, express high affinity and density bombes in (BBN) and neurotensin (NT) receptors on the tumor cell membrane. For this reason, BBN and NT are emerging as potential tools for their early diagnosis and therapy. This coordinated project aims at the development of radiolabeled BBN and NT analogs, that are useful either for the scintigraphic localization of BBN and NT receptor positive tumors and their metastases in vivo and/or for receptor associated therapy of these tumors.

For this purpose, peptide based analogs of prolonged plasma life and preserved biological action will be properly modified to incorporate radionuclides of choice. The main non invasive diagnostic modalities in Nuclear Medicine PET (positron emission tomography) and SPECT(single photon emission computerized tomography) require each the application of different radionuclides. Tagging of BBN and NT with the radiohalides 123/and 18F useful for SPECT and PET respectively will be initially pursued, as requiring the least possible alterations of peptide structure and consequently biological action. Modifications of the peptide backbone similar for both radiohalides--like incorporation of Tyr or Trp residues or coupling of aromatic groups at terminal amino acids-- will be attempted to achieve this goal. However, since 99mTc still remains the gold standard of Nuclear Medicine diagnosis using SPECT, suitable chelating systems will be coupled to the N-terminal amino acid of BBN and NT analog, to enable tagging with this metallic radionuclide. Similar modifications will be undertaken for developing a therapeutic receptor seeking agent carrying one of the two rheniumradionuclides 186Re and 188Re, since the Tc and Re chemistries are interrelated. Proper in vitro tests will demonstrate the suitability and effectiveness of these modifications. Eventually, in vivo experiments in healthy and tumor bearing animals will screen selected agents for clinical trials.05 05

Ámbito científico (EuroSciVoc)

• ciencias médicas y de la salud › medicina clínica › oncología › carcinoma broncopulmonar
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas
• ciencias médicas y de la salud › medicina clínica › radiología › medicina nuclear
• ciencias médicas y de la salud › medicina básica › patología
• ciencias médicas y de la salud › medicina básica › farmacología y farmacia › farmacocinética

Programa(s)

• FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998

Tema(s)

• 4.1.5 - Predisposition, early diagnosis and treatment

Convocatoria de propuestas

Datos no disponibles

Régimen de financiación

CSC - Cost-sharing contracts

Coordinador

Forschungszentrum Rossendorf e.V.

• Aportación de la UE: Sin datos
• Dirección: 01314 Dresden ; Alemania
• Coste total: Sin datos

Participantes (5)

Centre Hospitalier Universitaire Vaudois

Suiza

• Aportación de la UE: Sin datos
• Dirección: 46,Rue du Bugnon ; 1011 Lausanne
• Coste total: Sin datos

National Centre for Scientific Research 'Demokritos'

Grecia

• Aportación de la UE: Sin datos
• Dirección: Patriarchou Gregoriou street ; 15310 Athens
• Coste total: Sin datos

Paul Scherrer Institut

Suiza

• Aportación de la UE: Sin datos
• Dirección: 5232 Villigen
• Coste total: Sin datos

Universität Bern

Suiza

• Aportación de la UE: Sin datos
• Dirección: 31,Murtenstrasse ; 3010 Bern
• Coste total: Sin datos

Vrije Universiteit Brussel

Bélgica

• Aportación de la UE: Sin datos
• Dirección: 2,Pleinlaan ; 1050 Brussel
• Coste total: Sin datos