Developing novel non-invasive imaging techniques for cancer biomarkers
Todd Sasser, head of Applications Americas & Senior NMI Applications Specialist at Bruker discusses how imaging techniques are helping drug developers better target tumours in cancer patients.
Preclinical imaging plays a crucial role in understanding how the body works in both healthy and diseased states, and in describing responses to physiological or environmental changes. It provides important insights into disease processes at organ, tissue, cell, and molecular levels. Such knowledge informs the development of novel therapeutic strategies, which in turn improve patient outcomes and save lives. Preclinical imaging is also central to evaluating the effectiveness and safety of new treatments and describing drug distribution patterns before clinical use.
Cost-efficient and high-throughput longitudinal study of animal models can be achieved using anatomical evaluation techniques such as magnetic resonance imaging (MRI) and computed tomography (CT), alongside positron emission tomography (PET) and single-photon emission computed tomography (SPECT) for molecular visualisations. Small animal studies are necessary to explore and validate imaging agents in the preclinical phase, before beginning clinical trials. In this context, PET imaging is increasingly being used by researchers in the translational drug development phase as it provides data that can be extrapolated from animal to human studies.
Preclinical PET in oncology
The need to offer patients more personalised cancer treatment is driving advances in preclinical PET oncology research. The numerous different types of tumours – including those not yet well characterised – and their varying reactions to treatment, make the search for new effective cancer therapies incredibly challenging. Non-invasive in vivo imaging technologies such as PET enable researchers to better understand the course of tumour progression, by visualising cancer-related processes in real-time.
Such methods contribute to the growing knowledge-base of tumour morphology, progression, and biomarker expression. PET can provide information on the expression of receptors, energy metabolism, and other biomarkers of tumours by imaging an intravenously injected radiotracer. This radiotracer comprises a radioisotope, most commonly fluorine-18 (18F), attached to a molecule that targets a specific receptor or metabolic pathway, and its uptake by tumour cells is monitored.
“Conventional” PET tracers, such as 18F-FDG or 18F-Fluorothymidine (FLT), are considered the gold standard and monitor universal markers of tumour physiology, including altered metabolism and hypoxia, proliferation, and metastasis. More specific PET agents are being developed that are capable of targeting the expression of one molecule or gene product and have the potential to help researchers better understand and assess tumour biology and therapy responses.
Multi-modal technologies
As well as the development of novel PET tracers, integrating other imaging modalities, such as CT and MRI, can be applied to the investigation of tumour progression and characterise underlying biology. The CT component of PET/CT offers an anatomical reference and attenuation map for functional PET images and has been a valuable tool for a range of functions due to high-throughput, ease of use, and high-resolution for bone and pulmonary applications since the mid-1990s. However, PET/CT imaging still makes use of ionising radiation – a limitation that can be reduced by PET/MR technology. Its potential for multiparametric imaging and superior anatomical soft tissue contrast make PET/MR an increasingly popular method for preclinical oncology research. It offers the unique ability to detect tumour margins, evaluate tracer distribution within individual tumours to generate volume of interest, and calculate standardised uptake value (SUV) in a range of preclinical models, improving the functional analysis of complementary PET data. Whereas PET and CT data are acquired consecutively, some PET/MR systems acquire data simultaneously, allowing for complex imaging workflows.
In preclinical oncology, the excellent anatomical soft tissue contrast of PET/MR offers the unique ability to detect tumour margins/volumes in a broad range of models, which can improve the functional analysis of complementary PET data. MR has been shown to detect early stage Xenograft tumours, as well as orthotropic and spontaneous tumours in most organs at very early stages (Figure 1A). PET/MR provides a unique tool for interrogating the intricacies of a tumour microenvironment, owing to the achievable anatomical resolution of the tumour environment (Figure 1B) and may be enhanced by combined detections of factors such as perfusion/diffusion, protease activity, hypoxia, metabolites and metabolism (Figure 1C). Even individual variables (e.g. metabolism) can be interrogated with more refined precision using multiplex capabilities.
Developing tomorrow’s cancer treatments
The ongoing development of multi-modal PET technology will continue to drive preclinical oncology research. The benefits of PET, PET/MR, and PET/CT for tracer development, therapy monitoring and studying tumour biology are changing the way cancer is treated, moving towards a more personalised medicine approach. Cutting-edge research using advanced imaging instruments is bringing the field one step closer to personalised treatment and optimising cancer treatment and patient care.