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Preclinical in vivo cancer, straightway to patients?
Marion de Jong1, Stephen Mather2, Theodosia Maina3
1Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands - m.hendriks-dejong@erasmusmc.nl.
Abstract:
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.
Insights
Developing nuclear imaging probes for cancer requires rigorous preclinical testing. This process involves synthesis, in vitro and in vivo evaluation, and overcoming translation challenges for clinical oncology use.
Area of Science:
- Nuclear medicine
- Oncology
- Radiopharmaceutical science
Background:
- Personalized tumor-targeted imaging and therapy rely on effective cellular targets.
- Nuclear imaging probes, including radiolabeled antibodies and nanoparticles, are crucial for cancer research.
- Preclinical and translational studies are essential for developing clinical applications.
Purpose of the Study:
- To review preclinical studies of nuclear imaging probes for cancer.
- To outline the key steps in developing radiopharmaceuticals for clinical oncology.
- To highlight challenges and solutions in translating preclinical findings to clinical practice.
Main Methods:
- Synthesis and radiolabeling of potential nuclear probes.
- In vitro characterization, including target binding affinity assessment.
- In vivo evaluation using preclinical models and advanced imaging techniques (PET, SPECT, MRI, CT).
Main Results:
- Various radiolabeled probes (antibodies, peptides, nanoparticles) are evaluated for cancer imaging and therapy.
- Preclinical models and imaging platforms facilitate biodistribution, tumor targeting, and dosimetry studies.
- Successful candidates undergo toxicological assessments before clinical trials.
Conclusions:
- Rigorous preclinical evaluation is vital for advancing radiopharmaceuticals into clinical oncology.
- Development of specialized models and imaging platforms accelerates probe translation.
- Addressing confounding factors is key to successful clinical implementation of new nuclear probes.