Preclinical in vivo cancer, straightway to patients?
Detection of useful cellular targets has strongly stimulated personalized tumor-targeted imaging and therapy approaches, also involving synthesis and evaluation of nuclear imaging probes with potential for clinical applications. Reviews of preclinical and translational studies concerning such probes, including radiolabeled antibodies, nanobodies, affibodies, peptides, small molecule inhibitors, and nanoparticles, are presented in this issue. As most tracers described in these articles have been developed for the field of cancer imaging and radionuclide therapy, the current article on preclinical studies will focus on cancer research as well.
The main steps in developing a nuclear probe for clinical application for radionuclide imaging and therapy, after identification of a suitable molecular target on tumor cells, comprise:
1) synthesis and radiolabeling of the probe;
2) in vitro characterization, such as the evaluation of target binding affinity;
3) in vivo evaluation to assess the biodistribution and tumor targeting capability, for radionuclide therapy purposes also dosimetry studies to determine the absorbed doses and efficacy;
4) radiolabeled probes that successfully pass such tests as well as toxicological studies may enter clinical evaluation.
For preclinical testing of radiolabeled probes various relevant in vitro and in vivo models dedicated to oncological research have been developed along with preclinical imaging platforms, including positron emission tomography (PET) and single photon emission computed tomography (SPECT) systems, in combination with magnetic resonance imaging (MRI) or computed tomography (CT). These developments hold great promise for fast translation of new candidate probes from preclinical validation into the clinic. This overview article describes preclinical studies typically being performed to bring a new radiopharmaceutical into clinical oncology practice. It also aims to raise awareness of confounding factors during translation of preclinical studies and ways to overcome them.
|Keywords||Molecular imaging, Radioisotopes, Radiopharmaceuticals, Therapy|
|Persistent URL||dx.doi.org/10.23736/S1824-4785.17.02974-0, hdl.handle.net/1765/99173|
|Journal||Quarterly Journal of Nuclear Medicine and Molecular Imaging|
de Jong, M, Mather, S, & Maina, T. (2017). Preclinical in vivo cancer, straightway to patients?. Quarterly Journal of Nuclear Medicine and Molecular Imaging (Vol. 61, pp. 145–152). doi:10.23736/S1824-4785.17.02974-0