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Pretargeted
Radioimmunotherapy of Cancer: Progress Step by Step
Otto
C. Boerman, PhD, Frank G. van Schaijk, MSc, Wim J.G. Oyen, MD, PhD and Frans
H.M. Corstens, MD
Department
of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The
Netherlands
To
enhance the therapeutic efficacy of radioimmunotherapy of cancer,
several pretargeting strategies have been developed.
In pretargeted radioimmunotherapy, the tumor is pretargeted with
an antibody construct that has affinity for the tumor-associated antigen
on the one hand and for a radiolabeled hapten on the other.
The radiolabeled hapten is administered in a later phase, preferably
after the antibody construct has cleared from the circulation.
In pretargeted radioimmunotherapy, 2 main approaches can be
distinguished: pretargeting strategies based on the avid interaction
between streptavidin (SA) or avidin and biotin, and pretargeting
strategies based on the use of bispecific antibodies.
In pretargeting strategies based on biotin and SA or avidin, the
use of a clearing agent that could remove the pretargeting construct
from the circulation markedly improved the targeting of the
radiolabeled biotin to the tumor.
Thus, multistep injection schemes in which 3–5 different agents are
subsequently injected were developed.
In bispecific antibody-based pretargeting strategies, the use of
bivalent haptens improved the efficacy of the tumor targeting, and a
2-step pretargeted radioimmunotherapy strategy is now being tested in
cancer patients.
Preclinical studies as well as studies on cancer patients have shown
that these pretargeting strategies can result in higher radiation
doses to the tumor than can directly radiolabeled antitumor antibodies.
Here, the development and state of the art of the most effective
approaches for pretargeted radioimmunotherapy are reviewed.
Key
Words:
pretargeting, bispecific antibodies, avidin, streptavidin, biotin, radioimmunotherapy, radionuclide therapy
©
2003 by Society of Nuclear
Medicine
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