PT  - JOURNAL ARTICLE
AU  - Jean Claude Reubi
AU  - Helmut R. Maecke
TI  - Approaches to Multireceptor Targeting: Hybrid Radioligands, Radioligand Cocktails, and Sequential Radioligand Applications
AID  - 10.2967/jnumed.116.186882
DP  - 2017 Sep 01
TA  - Journal of Nuclear Medicine
PG  - 10S--16S
VI  - 58
IP  - Supplement 2
4099  - http://jnm.snmjournals.org/content/58/Supplement_2/10S.short
4100  - http://jnm.snmjournals.org/content/58/Supplement_2/10S.full
SO  - J Nucl Med2017 Sep 01; 58
AB  - Modern drug discovery highly depends on the identification and validation of the drug targets. Using the method of in vitro quantitative receptor autoradiography, we demonstrated that—for instance, in neuroendocrine tumors—up to 3 receptors can be coexpressed at a relatively high density. In addition, nonendocrine tumors such as breast, prostate, and brain tumors concomitantly express several G protein–coupled receptors at a high density. We propose 3 strategies for exploiting these findings for multireceptor targeting in vivo: use of heterobivalent or heteromultivalent ligands, which may bind simultaneously or monovalently to their different molecular targets; coinjection of a cocktail of radioligands; and sequential injection of different radioligands. Any of these strategies may help to remedy some of the major problems in cancer targeting: heterogeneity, change in phenotype during disease progression, and resistance.