PharmaAccelerating Go/No-Go Decisions with In Vivo Imaging in Radiopharmaceutical Development

Introduction

The development of targeted radionuclide therapy using therapeutic radiopharmaceuticals has quickly emerged as an accurate and efficient delivery of radiation directly to tumor cells. One of the main benefits of radiopharmaceutical drug delivery is the ability to target diseased cells whilst sparing healthy surrounding tissue. This transformative class of pharmaceuticals has seen a rapid increase in research and development over the last decade and more, with sponsors investing in next-generation radioligand therapy (RLT) programs to expand indications beyond established tumor types. As translational success continues to expand in this area, competition to identify optimal targets, payloads, and clinically viable combinations has intensified, placing an onus on sponsors to make appropriate go/no-go decisions when choosing and advancing specific drug candidates through development stages. This article will consider how preclinical imaging can accelerate go/no-go decisions in radiopharmaceutical development, with a particular focus on how PET and SPECT imaging can provide early insights into pharmacokinetics, tumor targeting, and therapeutic potential, reducing time and cost during preclinical development.

Preclinical in vivo imaging

‘In vivo’ is Latin for ‘within the living’, referring to a range of techniques used to visualize biological processes within living organisms. Preclinical in vivo imaging offers real-time, non-invasive insight into disease mechanisms, therapeutic effects, and drug behavior, allowing researchers to monitor disease progression, treatment response, and biological mechanisms in a way which closely mirrors human physiology. Across drug development, the use of in vivo imaging significantly reduces both the time it takes to advance a drug candidate through preclinical and clinical development stages and elicits significant cost savings, improving translational success and reducing the risk of late-stage candidate failures. Without in vivo imaging, it would be extremely difficult to progress scientific discoveries into effective treatments.

In relation to radiopharmaceutical drug development, its use is central to understanding whole-body distribution, organ-level uptake, dosimetry, and clearance. This is particularly important when you consider the inherent risks associated with systemic radiation exposure in human trials. In vivo imaging in radiopharmaceutical drug development integrates nuclear physics, molecular biology, and chemistry to create tracers which can visualize biological processes in real-time, giving researchers a much clearer understanding of how these compounds might behave in living systems. This includes insights into their biodistribution, target engagement, and potential accumulation in off-target tissues, all of which are essential elements for predicting efficacy and safety prior to first-in-human studies.

Translational imaging with PET SPECT oncology

Position emission tomography (PET) and single-photon emission computed tomography (SPECT) represent two advanced preclinical imaging solutions used to quickly identify the most promising compounds in radiopharmaceutical drug development. Technical advances in both PET and SPECT technology have significantly improved spatial resolution, sensitivity, and quantitative accuracy in small-animal imaging, increasing the translational value of animal models by enabling a more precise assessment of the biological processes relevant to human disease.

Key benefits include:

1. Real-time biodistribution analysis to assess tumor targeting and normal tissue uptake.
2. Quantitative dosimetry estimation to optimize therapeutic index and support safety assessment.
3. Evaluation of tumor retention and clearance to understand radiopharmaceutical behavior in vivo.
4. Detection of off-target organ exposure in tissues such as the liver, kidneys, and bone marrow.
5. Longitudinal imaging in the same animal to improve translational relevance and reduce study variability.
6. Earlier go/no-go decision-making through rapid identification of suboptimal candidates.

Regulatory bodies such as the FDA and EMA are increasingly emphasizing the importance of radiation safety, strict good manufacturing practices (GMP), and specialized non-clinical testing prior to human application. That being said, several technical and biological challenges exist which can limit sensitivity and quantification of radioligand therapy imaging, particularly in the context of radionuclide therapy, making a clinical trial imaging partner with radiopharmaceutical expertise essential for translational success.

Accelerating discovery with a clinical trial imaging partner

Perceptive, in vivo imaging CRO, facilitates a comprehensive array of non-invasive preclinical in vivo imaging techniques, helping to bridge the gap between preclinical insight and radiopharmaceutical trial success. With over 15 years of experience and a well-established global imaging infrastructure, Perceptive ensures rigorous scientific analysis and high-quality data to support radiopharmaceutical innovation.

From radiolabeling and biodistribution, to dosimetry and efficacy in diverse animal models, Perceptive delivers integrated, translatable data to accelerate your radiopharmaceutical pipeline from concept to clinic, making Perceptive well positioned help sponsors accelerate go/no-go decisions with in vivo imaging in radiopharmaceutical development.

Learn more about Perceptive Discovery Services today, or contact a Discovery solutions specialist.

Resources

Cells. Preclinical PET and SPECT Imaging in Small Animals: Technologies, Challenges and Translational Impact. https://www.mdpi.com/2073-4409/15/1/73

IEEE. In-vivo imaging of therapeutic radiopharmaceuticals with a developmental CZT-based SPECT. https://ieeexplore.ieee.org/document/10655999