Study of the labeling of two novel RGD-peptidic derivatives with the precursor [99mTc(H2O)3(CO)3]+ and evaluation for early angiogenesis detection in cancer.

In the initial stages of tumor formation, overexpression of integrins identifying the RGD sequence (Arg-Gly-Asp) is observed. The aim of the present study was the synthesis and labeling of two novel RGD derivatives, via the precursor [99mTc(H2O)3(CO)3]+, as well as the radiochemical and radiopharmacological evaluation of the labeled products. The labeling led to the formation of a single product in each case (>98%), with noteworthy in vitro stability, fast blood clearance and elimination by the hepatobiliary and the urinary systems.

Samarium-153 and technetium-99m-labeled monoclonal antibodies in angiogenesis for tumor visualization and inhibition.

BACKGROUND: Angiogenesis is the development of new blood vessels from pre-existing ones. Vascular endothelial growth factor (VEGF) is one of the most important angiogenic activators. Our studies are focused on the detection of VEGF by use of radiolabeled anti-endothelial monoclonal antibodies, which have the ability to localize in newly-formed vasculature of a cancerous origin. MATERIALS AND METHODS: The anti-endothelial monoclonal antibody VG76e was labeled with Samarium-153 and Technetium-99m. Biodistribution of the radiolabeled species was assessed in normal female Swiss mice, while tumor uptake was also evaluated. RESULTS: VG76e was labeled with 99mTc and 153Sm, resulting in a single product with a labeling yield of over 95%. Biodistribution studies showed non-specific uptake in any organ, with elimination via the hepatobiliary system. Finally, satisfactory tumor uptake was observed for both radiolabeled derivatives. CONCLUSION: Monoclonal antibodies raised against epithelial growth factors or their receptors, when labeled with appropriate radionuclides, may be a useful tool for early tumor detection and eventually for therapy.

Labeling of monoclonal antibodies with 153Sm for potential use in radioimmunotherapy.

The labeling of a monoclonal (anti-CEA) and a polyclonal (IgG) antibody with 153Sm has been investigated, using the bicyclic anhydride of DTPA (cDTPAa) as the chelating agent. The radiochemical study was performed using a combination of radioanalytical techniques (gel filtration, HPLC, ITLC-SG and SDS-PAGE). Optimization of factors affecting labeling (pH, Ab, Ab-DTPA concentration, etc.) leads to a labeling yield higher than 90%. Biodistribution studies in normal mice showed slow blood clearance and high uptake into the liver, kidney and lungs.

Synthesis, chemical, radiochemical and radiobiological evaluation of a new 99mTc-labelled bombesin-like peptide.

A new pentadecapeptide bombesin analogue was prepared by Fmoc synthesis, purified by HPLC and identified by electron ionization mass spectrometry. The biological activity of the new peptide was tested on isolated human colonic muscle cells and compared to native bombesin. Labelling of the new biomolecule with Tc-99m yielded a single radioactive species which remained stable at room temperature for eight hours. In a binding assay, the radiolabelled peptide showed high affinity for oat-cell carcinoma (Kd = 9.8 nM) and colorectal adenocarcinoma (Kd = 27.2 nM). Biodistribution studies, performed in normal rodents, indicated uptake by organs that normally express bombesin receptors, such as liver, intestines and kidneys. Scintigraphic studies, performed in nude mice transplanted with small cell lung carcinoma and colon cancer cells, showed significant tumor uptake two hours p.i. The new synthetic pentadecapeptide appears to have promise for several malignancies, including oat-cell lung carcinoma, colorectal cancer and gastroenteropancreatic (GEP) tumors.