Clinical Imaging in Drug Development

Clinical imaging is of great significance to drug development, and there is a growing need for imaging to provide information for drug development. From 1995 to 2004, nearly 30% of approved drugs for neuropsychiatric indications were developed with the help of imaging. A useful way to consider how imaging tools can contribute to clinical drug development is through their roles in solving major problems in drug development:

• Target validation
• Biodistribution
• Target interactions
• Pharmacodynamics
• Patient stratification and personalized medicine

New Drug Clinical Development Process

Drug discovery includes the identification of targets and the design and optimization of drugs to interact with them. Drug discovery and development can be divided into preclinical drug discovery, phase I trial, phase II trial, phase III trial, and FDA approval. The purpose of the first phase of the trial is mainly to study the pharmacokinetics and initial tolerance in humans. The phase II trial studied the safety and effectiveness of the drug in the case of problematic indications and sought to determine the best dose plan. The phase III study is to confirm the efficacy, tolerance, and safety of the new drug compared to standard treatment (or placebo), and to demonstrate the correct dose in cases where indications exist. Phase IV research needs to be carried out after registration.

Fig.1 The 5 steps from the drug development process. (Dillenseger, 2020)

Imaging in Pharmacokinetics Studies

In the first stage of clinical development, imaging has great potential in solving key mechanisms and therapeutic problems. Nuclear imaging technologies such as positron emission tomography (PET) provide the sensitivity needed to monitor drug distribution and pharmacokinetics (PK) as well as to image specific molecular endpoints. PET has been widely used in a variety of drugs to prove its activity in vivo. Using PET imaging technology to establish a dosing regimen has been pursued. Imaging modalities other than PET have also been used to evaluate drug delivery protocols.

Imaging in Pharmacodynamics and Drug Efficacy Studies

In many cases, the use of imaging biomarkers and alternative endpoints can promote small group size, fast results, and good statistical ability. Imaging biomarkers and alternative endpoints can be more objective and faster when evaluating the efficacy of new drugs. Imaging can reveal small and subtle changes, which indicate the gradual progress or regression that traditional methods may ignore. When choosing whether to use imaging surrogate endpoints, it is important to bear in mind that imaging surrogates are most helpful when the clinical outcome is difficult to assess; and those changes detected by imaging may not always reflect the true clinical outcomes.

Imaging in Drug Safety Assessment

There is huge potential for imaging in drug safety evaluation during clinical trials. Although in many cases drug safety information is better obtained through imaging, the information may also be obtained by histopathological means. In clinical trials, imaging can sometimes be the only practical means to obtain drug safety information. In addition, some structural and functional information is better acquired through imaging techniques. For example, the quantification of tissue lipid content is easier with MRI or MR Spectroscopy than histology techniques. Imaging provides a valuable tool in safety studies when other biomarkers for toxicity, such as routine serum chemistry measures are not suitable. MRI can offer advantages over methods that measure global functional changes by providing anatomically specific information on kidney injury.

Fig.2 Examples of procedures performed by NMTs and radiographers in a preclinical department. (Dillenseger, 2020)

Modern nuclear imaging techniques can noninvasively provide early in vivo assessment of bioactivity and help establish pharmacokinetic and pharmacodynamic profiles of new drugs. In phase I and phase II studies, imaging biomarkers may complement non-imaging endpoints to promote confidence of therapeutic efficacy or be used to study a drug’s mechanism of action. In phase III studies, imaging can secure or support regulatory approval for the new drug. With improvements in imaging hardware, software, and tracer development, the breadth of applications of imaging in new drug development is likely to increase.

To ensure adequate production quality and to assess the risks and benefits of medicines that treat disease, drugs must be approved by a regulatory medicines’ agency before use. Creative Biolabs provides powerful risk-based preclinical data verification services for drug research and development. We have a world-leading team of translational drug experts. You can rely on our powerful technology platform to advance your drug development faster and more effectively. Please feel free to contact us for more information.

Reference

1. Dillenseger, J.P.; et al. Why the preclinical imaging field needs nuclear medicine technologists and radiographers? Eur J Hybrid Imaging. 2020 Jul 20;4(1):12.