EVALUATION OF INDIUM-111-LABELED AND YTTRIUM-90-LABELED LINKER-IMMUNOCONJUGATES IN NUDE-MICE AND DOGS

Citation
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
Citations number
22
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging
ISSN journal
01615505
Volume
34
Issue
6
Year of publication
1993
Pages
938 - 945
Database
ISI
SICI code
0161-5505(1993)34:6<938:EOIAYL>2.0.ZU;2-2
Abstract
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.