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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Synthesis of new bivalent peptides for applications in the Affinity Enhancement System.

The feasibility of two-step radioimmunotherapy (RIT) of cancer by the Affinity Enhancement System ( AES) has been demonstrated in experimental and clinical studies. This technique, associating a bispecific antibody and a bivalent peptide radiolabeled with iodine-131, has been developed to reduce toxicity and to improve therapeutic efficacy compared to one-step targeting methods. The use of AES with different beta-emitters such as rhenium-188, samarium-153, or lutetium-177 or alpha-emitters such as actinium-225 or bismuth-213 is now considered. Thus three new peptides, designed to allow for the coupling of a variety of bifunctional chelating agents BCA, were synthesized by associating two glycyl-succinyl-histamine (GSH) arms, which are recognized by the 679 monoclonal antibody (mAb-679), with different binding agents, such as p-nitrophenylalanine or N,N-bis(carboxymethyl)-4-N'-(9-fluorenylmethyloxycarbonyl)aminobenzylamine. Immunoreactivity and serum stability evaluation were performed for each synthesized peptide. One of the three peptides (LM218) proved to be more stable than the others, and three different BCAs were coupled to LM218 (CITC-DTPA, CITC-TTHA, and CITC-CHXA''DTPA). One of these products, LM218-BzTTHA was radiolabeled with indium-111 without loss of immunoreactivity toward the mAb-679. These new peptides will allow pretargeted RIT with a large variety of radionuclides, to adapt the choice of the radionuclide (LET, half-life, penetrating emission) to the nature and size of targeted tumors.[1]

References

  1. Synthesis of new bivalent peptides for applications in the Affinity Enhancement System. Morandeau, L., Benoist, E., Loussouarn, A., Ouadi, A., Lesaec, P., Mougin, M., Faivre-Chauvet, A., Le Boterff, J., Chatal, J.F., Barbet, J., Gestin, J.F. Bioconjug. Chem. (2005) [Pubmed]
 
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