Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

FIG. 7.3. Pyrogen test shows results below 17.5 EU/mL.
A wide variety of radiometal chelated biotin derivatives have been
developed for application to pretargeting aimed at the radiotherapy of cancer.
Wilbur et al. reported novel studies focused on improving the in vivo behaviours
of radiohalogenated biotin derivatives for delivering 211 At in cancer pretargeting
protocols [7.16]. Because biotin derivatives are subject to in vivo degradation by
biotinidase, for optimal in vivo tumour targeting, it is essential to design conjugates
that are resistant to the enzymatic action while retaining a high binding affinity
towards avidin. First generation radiolabelled biotin conjugates had an amide
bond between the carboxylic group of biotin and the amino group of the spacer
carrying the chelating moiety, thus they were easily hydrolysable by biotinidase.
Avoiding enzyme degradation was then attempted by introducing steric hindrance
at the level of the amide bond (second generation). In this respect, Wilbur et al.
found that a carboxylate or hydroxymethylene group adjacent to the biotinamide
bond blocked the serum biotinamide hydrolysis, while the slow dissociation rate
of the biotin derivative from avidin was retained [7.17]. Foulon et al. impaired
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