Sm. Quadri et al., EVALUATION OF INDIUM-111-LABELED AND YTTRIUM-90-LABELED LINKER-IMMUNOCONJUGATES IN NUDE-MICE AND DOGS, The Journal of nuclear medicine, 34(6), 1993, pp. 938-945
Rapid uptake and slow transit of radioactivity from normal organs are
detrimental to any clinically utilized radioimmunoconjugate because th
ey lower the target-to-nontarget ratio and deliver undesirable radiati
on to normal organs. To mitigate this problem, two labile chemical lin
kages (EGS and DST) were introduced between a monoclonal antiferritin
antibody (QCI) and a chelating agent (DTPA). The biodistribution of la
bile-linker immunoconjugates (EGS and DST) and stable linker immunocon
jugates (DSS and ITCB) were compared. In a nude mouse model, all of th
e four immunoconjugates labeled with In-111 targeted subcutaneously-im
planted human tumor cells. Tumor-to-normal organ ratios were enhanced
for the EGS linkage in comparison to the two stable linkages. Serial w
hole-body immunoscintigraphy confirmed the biodistribution study. The
EGS and ITCB Y-90-labeled immunoconjugates had biodistributions simila
r to their respective In-111-labeled immunoconjugates. As the mouse mo
del is not representative of the high uptake of monoclonal antibodies
in the human liver, beagle dogs were used to further explore the reten
tion of radiolabel in normal liver. The EGS-linked immunoconjugate sig
nificantly reduced the dog liver activity when compared to the ITCB im
munoconjugate. The combination of the animal models (mouse and dog) ap
pears to allow for a more complete and optimal preclinical analysis of
chelated radiolabeled monoclonal antibodies for diagnosis or treatmen
t and illustrates the potential clinical improvements possible with la
bile chemical linkages in radioimmunoconjugates.