Abstract

There is a continous flow of novel radiopharmaceuticals orginating from preclinical research which hold promise for human applications. Translation to the clinic may prove challenging and development into procedures used in routine patient care is demanding.

As most radiopharmaceuticals are used in subpharmacological doses, toxicity is a minor issue. Nevertheless, rules and regulations are highly similar to those applicable to non-radioactive drugs that aim at a pharmacological effects. This results in time-consuming development, requiring significant resources that hamper introduction of novel radiopharmaceuticals in clinical research.

Nevertheless, there are several examples of succesful development of new radiolabeled agents. Somatostatin analogues can be considered the role model. After approval of the indium-111 labeled octreotide for somatostatin subtype receptor 2 imaging, a wealth of derivatives for imaging (first for SPECT and later for PET) as well as peptide receptor radionulide therapy with Y-90 and Lu-177 labeled peptides were developed. It took many years to arrive at a registration trial for the therapeutic Lu-177 octreotate, which has been completed recently. A more recent example is the development of  highly promising radiolabeled PSMA-ligands for imaging and treatment of prostate cancer.

Radiolabeled antibodies are another class of radiopharmaceuticals used for experimental cancer imaging and therapy. For-human-use antibody production with the sole purpose of nuclear medicine applications rarely occurs. The widespread use of unlabeled antibodies for treatment of many cancer types opened the door for molecular imaging with radiolabeled antibodies, mainly for translational research. The possibility to actually depict the receptor status and the targeting potential of these drugs is a very attractive concept to study heterogeneity of receptor expression and tumor penetration of the antibodies in-vivo.

In conclusion, despite the non-trivial hurdles in bringing radiopharmaceuticals to the clinic, they are great assets for molecular imaging of cancer for characterization of tumors, staging and therapy response prediction.