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TE1PA as Innovating Chelator for 64Cu Immuno-TEP Imaging: A Comparative in Vivo Study with DOTA/NOTA by Conjugation on 9E7.4 mAb in a Syngeneic Multiple Myeloma Model.
Navarro, Anne-Sophie; Le Bihan, Thomas; Le Saëc, Patricia; Bris, Nathalie Le; Bailly, Clément; Saï-Maurel, Catherine; Bourgeois, Mickaël; Chérel, Michel; Tripier, Raphaël; Faivre-Chauvet, Alain.
Afiliación
  • Navarro AS; CRCINA, INSERM 1232-CNRS ERL 6001, University of Angers, University of Nantes , 8 quai Moncousu , 44007 Nantes , France.
  • Le Bihan T; University Hospital , 44000 Nantes , France.
  • Le Saëc P; Univ Brest , UMR-CNRS CEMCA 6521, 6 avenue Le Gorgeu , 29200 Brest , France.
  • Bris NL; CRCINA, INSERM 1232-CNRS ERL 6001, University of Angers, University of Nantes , 8 quai Moncousu , 44007 Nantes , France.
  • Bailly C; Univ Brest , UMR-CNRS CEMCA 6521, 6 avenue Le Gorgeu , 29200 Brest , France.
  • Saï-Maurel C; CRCINA, INSERM 1232-CNRS ERL 6001, University of Angers, University of Nantes , 8 quai Moncousu , 44007 Nantes , France.
  • Bourgeois M; University Hospital , 44000 Nantes , France.
  • Chérel M; CRCINA, INSERM 1232-CNRS ERL 6001, University of Angers, University of Nantes , 8 quai Moncousu , 44007 Nantes , France.
  • Tripier R; University Hospital , 44000 Nantes , France.
  • Faivre-Chauvet A; CRCINA, INSERM 1232-CNRS ERL 6001, University of Angers, University of Nantes , 8 quai Moncousu , 44007 Nantes , France.
Bioconjug Chem ; 30(9): 2393-2403, 2019 09 18.
Article en En | MEDLINE | ID: mdl-31386357
ABSTRACT
Following the successful synthesis of a C-functionalized version of the TE1PA ligand, a monopicolinate cyclam, we looked to demonstrate its in vivo properties versus DOTA and NOTA, after conjugation on the 9E7.4 rat antibody, an IgG2a against CD138 murine, which has relevant properties for multiple myeloma targeting. For each ligand, different conjugation approaches had been considered to select the most appropriate for the comparative study. The p-SCN-Bn-TE1PA, NHS-DOTA, and p-SCN-Bn-NOTA were finally chosen for conjugation and radiolabeling tests. For in vivo comparison, we used a model of subcutaneous grafted mice with 5T33 tumor cells. In vitro tests and immuno-PET study highlighted 64Cu-9E7.4-p-SCN-Bn-NOTA as the least attractive. Further competitive biodistribution and hepatic metabolic studies at 2, 24, and 48 h post-injection (100 µg radiolabeled with 10 MBq of 64Cu) were then performed with the 64Cu-9E7.4-p-SCN-Bn-TE1PA and 64Cu-9E7.4-NHS-DOTA. Results show a better in vivo resistance of 64Cu-9E7.4-p-SCN-Bn-TE1PA to transchelation compared to 64Cu-9E7.4-NHS-DOTA, especially at later times. This was confirmed with 64Cu-9E7.4-p-SCN-Bn-NOTA at 48 h PI. 64Cu-9E7.4-p-SCN-Bn-TE1PA also demonstrated an excellent hepatic clearance. 64Cu-9E7.4-p-SCN-Bn-TE1PA displayed an overall superiority compared to 64Cu-9E7.4-NHS-DOTA and 64Cu-9E7.4-p-SCN-Bn-NOTA in terms of in vivo stability, reinforcing the usefulness of the p-SCN-Bn-TE1PA ligand for 64Cu immuno-PET imaging.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Radioisótopos de Cobre / Quelantes / Tomografía de Emisión de Positrones / Compuestos Heterocíclicos con 1 Anillo / Anticuerpos Monoclonales / Mieloma Múltiple Límite: Animals Idioma: En Revista: Bioconjug Chem Asunto de la revista: BIOQUIMICA Año: 2019 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Radioisótopos de Cobre / Quelantes / Tomografía de Emisión de Positrones / Compuestos Heterocíclicos con 1 Anillo / Anticuerpos Monoclonales / Mieloma Múltiple Límite: Animals Idioma: En Revista: Bioconjug Chem Asunto de la revista: BIOQUIMICA Año: 2019 Tipo del documento: Article País de afiliación: Francia