TY - JOUR
T1 - Radiolabelling of the octadentate chelators DFO* and oxoDFO* with zirconium-89 and gallium-68
AU - Brandt, Marie
AU - Cowell, Joseph
AU - Aulsebrook, Margaret L.
AU - Gasser, Gilles
AU - Mindt, Thomas L.
N1 - Funding Information:
This work was funded by the Swiss National Science Foundation (Grant no. SNSF 205321_157216 to G.G. and T.L.M). The authors thank Katarina Ben?urov? (Ludwig Boltzmann Institute Applied Diagnostics) and Jonas Aronow (Medical University of Vienna) for technical assistance.
Funding Information:
This work was funded by the Swiss National Science Foundation (Grant no. SNSF 205321_157216 to G.G. and T.L.M). The authors thank Katarina Benčurová (Ludwig Boltzmann Institute Applied Diagnostics) and Jonas Aronow (Medical University of Vienna) for technical assistance.
Publisher Copyright:
© 2020, Society for Biological Inorganic Chemistry (SBIC).
PY - 2020
Y1 - 2020
N2 - Abstract: In recent years, clinical imaging with zirconium-89 (89Zr)-labelled monoclonal antibodies (Ab) by positron emission tomography (immunoPET) has been gaining significant importance in nuclear medicine for the diagnosis of different types of cancer. For complexation of the radiometal 89Zr and its attachment to the Ab, chelating agents are required. To date, only the hexadentate chelator desferrioxamine (DFO) is applied in the clinic for this purpose. However, there is increasing preclinical evidence that the [89Zr]Zr-DFO complex is not sufficiently stable and partly releases the radiometal in vivo due to the incomplete coordination sphere of the metal. This leads to unfavourable unspecific uptake of the osteophilic radiometal in bones, hence decreasing the signal-to-noise-ratio and leading to an increased dose to the patient. In the past, several new chelators with denticities > 6 have been published, notably the octadentate DFO derivative DFO*. DFO*, however, shows limited water solubility, wherefore an oxygen containing analogue, termed oxoDFO*, was developed in 2017. However, no data on the suitability of oxoDFO* for radiolabelling with 89Zr has yet been reported. In this proof-of-concept study, we present the first radiolabelling results of the octadentate, water-soluble chelator oxoDFO*, as well as the in vitro stability of the resulting complex [89Zr]Zr-oxoDFO* in comparison to the analogous octadentate, but less water-soluble derivative DFO* and the current “standard” chelator DFO. In addition, the suitability of DFO* and oxoDFO* for radiolabeling with the short-lived PET metal gallium-68 is discussed. Graphic abstract: The water-soluble, octadentate chelator oxoDFO* provides stable complexes with the positron emitter Zirconium-89. The radiolabelling can be performed at room temperature and neutral pH and thus, oxoDFO* represents a promising chelator for applications in immunoPET.[Figure not available: see fulltext.].
AB - Abstract: In recent years, clinical imaging with zirconium-89 (89Zr)-labelled monoclonal antibodies (Ab) by positron emission tomography (immunoPET) has been gaining significant importance in nuclear medicine for the diagnosis of different types of cancer. For complexation of the radiometal 89Zr and its attachment to the Ab, chelating agents are required. To date, only the hexadentate chelator desferrioxamine (DFO) is applied in the clinic for this purpose. However, there is increasing preclinical evidence that the [89Zr]Zr-DFO complex is not sufficiently stable and partly releases the radiometal in vivo due to the incomplete coordination sphere of the metal. This leads to unfavourable unspecific uptake of the osteophilic radiometal in bones, hence decreasing the signal-to-noise-ratio and leading to an increased dose to the patient. In the past, several new chelators with denticities > 6 have been published, notably the octadentate DFO derivative DFO*. DFO*, however, shows limited water solubility, wherefore an oxygen containing analogue, termed oxoDFO*, was developed in 2017. However, no data on the suitability of oxoDFO* for radiolabelling with 89Zr has yet been reported. In this proof-of-concept study, we present the first radiolabelling results of the octadentate, water-soluble chelator oxoDFO*, as well as the in vitro stability of the resulting complex [89Zr]Zr-oxoDFO* in comparison to the analogous octadentate, but less water-soluble derivative DFO* and the current “standard” chelator DFO. In addition, the suitability of DFO* and oxoDFO* for radiolabeling with the short-lived PET metal gallium-68 is discussed. Graphic abstract: The water-soluble, octadentate chelator oxoDFO* provides stable complexes with the positron emitter Zirconium-89. The radiolabelling can be performed at room temperature and neutral pH and thus, oxoDFO* represents a promising chelator for applications in immunoPET.[Figure not available: see fulltext.].
KW - Chelators
KW - DFO
KW - Gallium-68
KW - Positron emission tomography (PET)
KW - Zirconium-89
UR - http://www.scopus.com/inward/record.url?scp=85087823422&partnerID=8YFLogxK
U2 - 10.1007/s00775-020-01800-4
DO - 10.1007/s00775-020-01800-4
M3 - Article
C2 - 32661784
AN - SCOPUS:85087823422
SN - 0949-8257
VL - 25
SP - 789
EP - 796
JO - Journal of Biological Inorganic Chemistry
JF - Journal of Biological Inorganic Chemistry
IS - 5
ER -
