Rapidly (and Successfully) Translating Novel Brain Radiotracers From Animal Research Into Clinical Use

Abstract

The advent of preclinical research scanners for in vivo imaging of small animals has added confidence into the multi-step decision-making process of radiotracer discovery and development. Furthermore, it has expanded the utility of imaging techniques available to dissect clinical questions, fostering a cyclic interaction between the clinical and the preclinical worlds. Significant efforts from medicinal chemistry have also made available several high-affinity and selective compounds amenable for radiolabeling, that target different receptors, transporters and enzymes in vivo . This substantially increased the range of applications of molecular imaging using positron emission tomography (PET) or single photon emission computed tomography (SPECT). However, the process of developing novel radiotracers for in vivo imaging of the human brain is a multi-step process that has several inherent pitfalls and technical difficulties, which often hampers the successful translation of novel imaging agents from preclinical research into clinical use. In this paper, the process of radiotracer development and its relevance in brain research is discussed; as well as, its pitfalls, technical challenges and future promises. Examples of successful and unsuccessful translation of brain radiotracers will be presented.

Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas

“…In the following two subsections, we will briefly summarize the most important aspects, with a focus on considerations specific to the development of mIDH-selective PET tracers from existing inhibitors. For more detailed discussions of the general requirements for PET neurotracers, readers are referred to several previous reviews on the topic [ 48 , 49 , 50 , 51 ].…”

“…The development of novel PET tracers for brain imaging is associated with several potential pitfalls and challenges, most of which are related to the strict requirements that need to be fulfilled [ 48 , 49 , 50 , 51 ]. For example, a common reason for the failure of PET neurotracers is limited brain entry due to low passive permeability and/or active export across the blood–brain barrier (BBB).…”

Recent Technical Advances in Accelerating the Clinical Translation of Small Animal Brain Imaging: Hybrid Imaging, Deep Learning, and Transcriptomics

“…Imaging biomarker generates added value by facilitating drug development, monitoring of treatment response ( 99 ), and reducing cost per quality-adjusted life year gained by enabling early diagnosis ( 100 ). Closing the translational gaps requires enormous technical, biological, and clinical validation and also cost effectiveness assessment ( 101 ). The lack of a satisfactory animal model is a shared problem for research on brain diseases, including stroke, neurodegenerative diseases, psychiatric diseases, and multiple sclerosis ( 102 ).…”

Application of Advanced Imaging Modalities in Veterinary Medicine: A Review

“…It also provides imaging biomarkers to track disease development and monitor the effects of drugs on disease progression and used to determine optimal dosing for new drugs via microdosing experimental setup and can aid with accelerating the implementation of personalized medicine. 89 , 90 …”