Deferoxamine as a chelator for 67Ga in the preparation of antibody conjugates.
(67)Ga antibodies (Abs) have been shown to be effective agents for single-cell killing due to the Auger electrons emitted, but their specific activities have not been as high as desired. We therefore evaluated deferoxamine (DFO) as a chelator, as opposed to the cyclic chelator NOTA, which was used previously. Use of DFO for Ab conjugation to (67)Ga was reported previously by several laboratories. DFO was conjugated to Abs by two methods, one using Ablysine conjugation and another using mild reduction of Abs to generate thiols in the hinge region. Labeling with (67)Ga was efficient, and the specific activities obtained under nonoptimized conditions were twice as high as those achieved previously. However, analysis of these conjugates revealed two problems that appear to prevent their further development. First, the stability was inadequate for the 3-day half-life of the nuclide. Second, the labels were poorly retained within cells after Ab internalization and catabolism. Also, it was found that stability was significantly affected by the incubation buffer used: buffers lacking physiological concentrations of divalent cations Ca and Mg resulted in much lower stability than buffers including them. In conclusion, DFO does not seem to be a suitable chelator for (67)Ga conjugation for our purposes.
Govindan
Serengulam V
SV
Immunomedics, Inc., Morris Plains, NJ 07950, USA.
Michel
Rosana B
RB
Griffiths
Gary L
GL
Goldenberg
David M
DM
Mattes
M Jules
MJ
D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry*; D003676:Deferoxamine / Q000737:chemistry*; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000494:pharmacology; D007553:Isotope Labeling; D016499:Radioimmunotherapy
D002614:Chelating Agents; D005710:Gallium Radioisotopes; D018796:Immunoconjugates; D003676:Deferoxamine