Preclinical Molecular Imaging Group

Dr Gabriela Kramer-Marek’s group uses cutting-edge biomedical imaging techniques to gain information about the way particular genes drive cancer progression.

Our group’s long-term goal is to develop specific biomarkers for detecting cancers and to evaluate these biomarkers in pre-clinical cancer models

Notwithstanding the remarkable clinical success of mAb-based treatment regimens, not all patients benefit from them. This can be attributed, at least in part, to the complexity of the tumour microenvironment and its considerable heterogeneity both in terms of the tumour and non-tumour cell components. These phenomena represent a huge challenge in identifying predictive biomarkers and stratifying patient populations for personalised therapy approaches.

Therefore, there is an urgent need to develop assays that will help in three ways:

  1. accurate patient selection
  2. understanding intrinsic resistance mechanisms or the emergence of acquired resistance following treatment initiation and
  3. choosing the most effective combination regimen in circumstances in which single-agent therapies are insufficiently effective.

Currently, the baseline expression level of antigens targeted by therapeutic mAbs can be analysed by methods such as: immunohistochemistry (IHC), flow cytometry, proteomics, or next-generation sequencing of tumour tissues acquired at diagnostic biopsy or intra-operatively. These techniques aid our understanding of how cancer cells adapt to treatment and become resistant, but such methods are inherently invasive, prone to sampling errors caused by inter- and intra-tumour heterogeneity of receptor expression within analysed biopsy specimens and do not lend themselves readily to repeated sampling.

Positron emission tomography (PET), using radiolabelled mAbs, antibody fragments or engineered protein scaffolds (immuno-PET), has the potential to acquire information non-invasively and can be highly complementary to analyses based on tissue acquisition. Accordingly, immuno-PET agents might accurately identify the presence and accessibility of the target and provide a rapid assessment of tumour response to a variety of treatments in a timely fashion (e.g. within 1-2 weeks of treatment initiation).

Furthermore, immuno-PET agents can provide information about the heterogeneity of both target expression and therapeutic response, which are increasingly recognised as key factors in treatment resistance. This especially relates to patients with advanced disease in whom target expression may vary from site to site and a biopsy of a single local or metastatic deposit may not accurately reflect the situation across the entire disease burden. Although introduction of immuno-PET into routine clinical practice may add complexity and increase costs, with appropriate use this imaging modality has the potential to identify patients likely to benefit from therapy and assess the efficacy of novel target-specific drugs.

Against this background, our research focuses on the development and characterisation of targeted-PET radiotracers, including protein-based theranostic agents that enable smart monitoring of immunotherapies and expand opportunities for personalised medicine approaches.

Early diagnosis and individualized therapy have been recognized as crucial for the improvement of cancer treatment outcome. While proper molecular characterization of individual tumour types facilitates choice of the right therapeutic strategies, early assessment of tumour response to therapy could allow the physicians to discontinue ineffective treatment and offer the patient a more promising alternative. Therefore, the role of molecular imaging in elucidating molecular pathways involved in cancer progression and the ability to select the most effective therapy based on the unique biologic characteristics of the patient and the molecular properties of a tumour are undoubtedly of paramount importance.

The mission of this group is to investigate innovative imaging probes and apply them to novel orthotopic or metastatic models that are target driven, to gain information of the way particular oncogenes drive cancer progression through signalling pathways that can be imaged in vivo and, correlate it with target level ex vivo. Such an approach enables non-invasive assessment of biochemical target levels, target modulation and provides opportunities to optimize the drug dosing for maximum therapeutic effect, which leads to the development of better strategies for the more precise delivery of medicine.

The long term goal of our research is to develop specific imaging cancer biomarkers, especially for positron emission tomography (PET) as well as optical imaging and, evaluate these biomarkers in pre-clinical cancer models. Significant efforts are directed towards validating biomarkers for early prediction of treatment response, with the focus on new targeted therapies (such as inhibition of cell signalling pathways).

Our initial portfolio of imaging agents include radiolabelled affibody molecules, TK inhibitors and, conventional tracers that monitor universal markers of tumour physiology.

We are actively supported by other groups from the Division of Radiotherapy and Imaging as well as the Division of Cancer Therapeutics. Moreover, our close association with The Royal Marsden NHS Foundation Trust enables rapid translation of our research to early clinical studies and ensures a fast transition of know-how from the research laboratory to the patient bedside.

Dr Gabriela Kramer-Marek

Group Leader:

Preclinical Molecular Imaging Gabriela Kramer-Marek

Dr Gabriela Kramer-Marek is investigating new ways of molecular imaging in order to predict an individual patient’s response to treatment. Before moving to the ICR, she developed a new approach for non-invasive assessment of HER2 expression in breast cancer.

Researchers in this group

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Phone: 020 3437 6376

Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 6785

Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 6857

Email: [email protected]

Location: Sutton

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Phone: 020 3437 4549

Email: [email protected]

Location: Sutton

Dr Gabriela Kramer-Marek's group have written 63 publications

Most recent new publication 10/2024

See all their publications

Recent discoveries from this group

23/01/25

Scientists have successfully used a form of artificial intelligence (AI) to develop a new imaging approach that makes it easier for radiologists to assess the extent of bone disease in people with advanced prostate cancer or multiple myeloma.

The research team has developed a software solution that minimises variability in the images achieved from whole-body diffusion-weighted imaging (WBDWI) scans, making them quicker and easier to compare across time and scanner sites. WBDWI is a commonly used non-invasive technique that makes it possible to detect and assess how secondary bone cancer progresses and responds to treatment.

This software should improve the detection of disease progression during treatment, meaning that clinicians could intervene early and switch the treatment if the disease is not responding. This could improve and even extend the lives of people with various cancers that have spread to the bones.

The work was led by scientists at The Institute of Cancer Research, London, and it was funded by the National Institute for Health and Care Research’s (NIHR’s) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (ICR). The paper was published in the journal Bioengineering.

Together with its partner hospital, The Royal Marsden, the ICR has an impressive track record of practice-changing advances in imaging and radiotherapy. Since completing this new study, the ICR has worked with a commercial partner, Mint Medical, to exploit this novel method of analysing WBDWI data collected using routine imaging protocols. The partnership has created a clinical tool that will be brought into medical practice.

Overcoming a longstanding MRI challenge

WBDWI is a form of MRI that measures the movement of water molecules in bodily tissues. It can distinguish between cancerous and non-cancerous tissues, helping with both the diagnosis and monitoring of the disease.

Currently, it is primarily used to detect and assess treatment response in people with advanced prostate and breast cancer that has spread to the bones. However, while WBDWI offers several benefits – such as being non-invasive and not requiring radiation or a contrast dye – it does pose some obstacles.

Until now, it has been hard for scientists to compare the images obtained from the same person at different times. This is due to fluctuations in the body, such as changes in blood flow and cell activity, that affect the movement of water molecules in its tissues. In addition, differences in MRI scanner settings mean that it is often not feasible to compare images achieved using different scanners.

This limitation makes it difficult for clinicians to determine the extent to which bone disease is changing over time and in response to treatment. In addition, it hinders the development of automated tools that could draw on multiple sets of images to provide this information in a short amount of time, which would be extremely useful in a clinical setting.

Developing a fully automated workflow

The scientists behind this study wanted to create a clinical tool that standardises the white, grey and black shading across WBDWI images to make them directly comparable.

They decided to do this using machine learning, which teaches computers to process data in a specific way. They trained their deep learning model using images of the spinal canal in 40 people with advanced prostate cancer or multiple myeloma. Each participant underwent two WBDWI scans – a baseline scan and a follow-up one – to assess their response to treatment. This provided a total of 8,749 images for training the model and an additional 2,758 images for validating it. The information provided by the model was then manually verified by radiologists with expertise in WBDWI.

The model was able to provide accurate measurements of the movement of water within tissues, reflecting the estimated tumour burden within the skeleton. These measurements can serve as biomarkers of response to treatment. Importantly, it was able to do this in less than three minutes, using WBDWI data alone and not affecting the contrast between the tissue of interest and the surrounding tissue.

The team is now evaluating the new tool in a clinical trial to ensure that it can effectively provide information about bone disease from WBDWI in a larger-scale multi-centre setting.

A robust approach

Senior author Dr Matthew Blackledge, leader of the Computational Imaging Group in the Division of Radiotherapy and Imaging at the ICR, said:

“At the moment, clinicians are having to rely on manual interpretation of scan images, which is time-consuming and not feasible in clinical practice.

“As a result of our latest work, radiologists will now be able to quickly assess the extent of bone disease and monitor changes in follow-up scans without manually adjusting contrast. Additionally, WBDWI allows the measurement of a surrogate imaging biomarker that correlates with tumour invasiveness.

“We’re hopeful that our software solution will improve the quantification of disease extent and treatment response to such a level that it leads to significant improvements in patient outcomes.”

First author Antonio Candito, Postdoctoral Training Fellow in the Computational Imaging Group at the ICR, said:

“Our model’s ability to generalise across multi-centre WBDWI datasets was surprising because this is a challenge we have long faced in machine learning. Its ability to demonstrate repeatable and reliable outcomes across different cancer types, follow-up scans, protocols and MRI scanners is indicative of the robustness of our approach.

“Our method is inspired by the preference of experienced clinicians using whole-body MRI in oncology, and we believe it will assist them in detecting disease progression within three months of treatment initiation.

“We are excited to see the results of the ongoing clinical trial, which may lead to changes in the standard care of people with bone disease.”