TY - JOUR
T1 - What is the best radionuclide for immuno-PET of multiple myeloma? A comparison study between89 zr-and64 cu-labeled anti-CD138 in a preclinical syngeneic model
AU - Bailly, Clément
AU - Gouard, Sébastien
AU - Guérard, François
AU - Chalopin, Benjamin
AU - Carlier, Thomas
AU - Faivre-Chauvet, Alain
AU - Saëc, Patricia Remaud Le
AU - Bourgeois, Mickaël
AU - Chouin, Nicolas
AU - Rbah-Vidal, Latifa
AU - Tripier, Raphaël
AU - Haddad, Ferid
AU - Kraeber-Bodéré, Françoise
AU - Bodet-Milin, Caroline
AU - Chérel, Michel
PY - 2019/2
Y1 - 2019/2
N2 - Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18 F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64 Cu) or zirconium-89 (89 Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for64 Cu and89 Zr labeling, respectively.64 Cu-TE2A-9E7.4 and89 Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to18 F-FDG-PET imaging. In biodistribution and PET studies,64 Cu-TE2A-9E7.4 and89 Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with64 Cu-TE2A-9E7.4 and89 Zr-DFO-9E7.4 showed higher uptake than with18 F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of89 Zr-DFO-9E7.4 than64 Cu-TE2A-9E7.4. Because of free89 Zr’s tropism for bone when using89 Zr-anti-CD138,64 Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.
AB - Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18 F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64 Cu) or zirconium-89 (89 Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for64 Cu and89 Zr labeling, respectively.64 Cu-TE2A-9E7.4 and89 Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to18 F-FDG-PET imaging. In biodistribution and PET studies,64 Cu-TE2A-9E7.4 and89 Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with64 Cu-TE2A-9E7.4 and89 Zr-DFO-9E7.4 showed higher uptake than with18 F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of89 Zr-DFO-9E7.4 than64 Cu-TE2A-9E7.4. Because of free89 Zr’s tropism for bone when using89 Zr-anti-CD138,64 Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.
KW - Copper-64
KW - Immuno-PET
KW - Multiple myeloma
KW - Murine CD138
KW - Zirconium-89
UR - https://www.mendeley.com/catalogue/2cfedd48-8ff8-3302-85f9-b3705c0ffa82/
U2 - 10.3390/ijms20102564
DO - 10.3390/ijms20102564
M3 - Article
C2 - 31137758
SN - 1661-6596
VL - 20
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 10
ER -