Exploring Tumor Heterogeneity Using PET Imaging: The Big Picture

Abstract

Personalized medicine represents a major goal in oncology. It has its underpinning in the identification of biomarkers with diagnostic, prognostic, or predictive values. Nowadays, the concept of biomarker no longer necessarily corresponds to biological characteristics measured ex vivo but includes complex physiological characteristics acquired by different technologies. Positron-emission-tomography (PET) imaging is an integral part of this approach by enabling the fine characterization of tumor heterogeneity in vivo in a non-invasive way. It can effectively be assessed by exploring the heterogeneous distribution and uptake of a tracer such as 18F-fluoro-deoxyglucose (FDG) or by using multiple radiopharmaceuticals, each providing different information. These two approaches represent two avenues of development for the research of new biomarkers in oncology. In this article, we review the existing evidence that the measurement of tumor heterogeneity with PET imaging provide essential information in clinical practice for treatment decision-making strategy, to better select patients with poor prognosis for more intensive therapy or those eligible for targeted therapy.

Correlations between baseline 18F-FDG PET tumour parameters and circulating DNA in diffuse large B cell lymphoma and Hodgkin lymphoma

“…These parameters belong to the "shape" and "intensity" parameter types [22]. Some other parameters, including "textural" parameters used to determine the heterogeneity of the tumours [9], could be interesting with possible links between DNA parameters (in bloodstream or in tumour biopsy) and PET parameters. However, most of the "textural" parameters are mathematically designed to characterize unique tumour [10,23] and have therefore to be applied on the largest lymphoma lesion which could be representative of the disease, notably to predict survival [24].…”

“…However, if thousands of different radiomical features, including "textural" features, can be extracted and analysed from medical images [6,7], most of them can be applied only on unique tumours, while lymphomas are, most of the time, multisite tumours and it is possible that textural features are therefore less effective in lymphomas. Therefore, if entropy, a parameter among the textural features exploring the relationships between the tumour pixels, seems to be a prognostic factor for mantle cell lymphoma [8,9], it is usually difficult to extract and analyse "textural" parameters when multiple tumours are considered because they are mathematically designed for unique tumour [10]. For multisite tumours, like lymphomas, parameters describing the tumour burden, tumour fragmentation/massiveness, tumour dispersion and tumour activity seem particularly relevant.…”

Use of imaging to assess the activity of hepatic transporters

“…PET is routinely used in clinical oncology as a diagnostic tool, but it is also commonly used to address different research questions in experimental medicine [39][40][41][42][43]. It can for instance be used to assess various aspects of brain and heart function and it has been widely used in drug development [44].…”

Early Prediction of Tumor Response to Neoadjuvant Chemotherapy and Clinical Outcome in Breast Cancer Using a Novel FDG-PET Parameter for Cancer Stem Cell Metabolism

“…Advanced tumors are thus comprised of cancer cells with varying levels of differentiation, consequently leading to cancer cell subsets exerting differential biological traits [5]. Recently, radiomics has been used to measure the intratumoral heterogeneity using texture analysis [6,7], but it has a major drawback. The results are not consistent across the studies [6,8].…”