Can radioimmunotherapy promote from an orphan drug to daily clinical practice?

Excerpt

The concept of using radiolabelled antibodies to deliver radiation specifically to cells expressing specific antigens has a longstanding history in preclinical nuclear medicine research [1‐3]. Several approaches were used as long ago as some 50 years to evaluate the potential therapeutic effect in different xenograft models [2, 3]. Promising results were shown in different tumour cell lines in vitro and in vivo [4‐7]. One of the first human applications was reported in the late 1960s [8]. All these studies have in common that they used heterologous antibodies generated in different species and mostly labelled with ¹³¹I. Due to the large size of complete antibodies they display a less favourable biodistribution pattern. One of the important aspects is a rather long blood-pool half-life which leads to an increased risk of deiodination and thereby the risk of an increased dose to the thyroid and at the same time lower accumulation in the targeted tumour. Other radionuclides such as ⁹⁰Y [9], ¹⁷⁷Lu [10] or different alpha-emitters (see for example Chen et al. [11]) might be more effective due to a expected higher linear energy transfer and a higher stability in vivo. Furthermore, complete antibodies are more easily recognized by FcR-expressing cells such as macrophages and granulocytes. Another point is the expected diminished capacity for penetration into tumours due to the size of the antibodies. …