Warburg revisited: imaging tumour blood flow and metabolism

Abstract

In the 1930s, Otto Warburg reported that anaerobic metabolism of glucose is a fundamental property of all tumours, even in the presence of an adequate oxygen supply. He also demonstrated a relationship between the degree of anaerobic metabolism and tumour growth rate. Today, this phenomenon forms the basis of tumour imaging with fluorodeoxyglucose positron emission tomography (FDG-PET). More recently, Folkman has demonstrated that malignant growth and survival are also dependent on tumour vascularity which is increasingly evaluated in vivo using techniques such as contrast enhanced computed tomography or magnetic resonance imaging (MRI). Although it is reasonable to hypothesise that the metabolic requirements of tumours are mirrored by alterations in tumour haemodynamics, the relationship between tumour blood flow and metabolism is in fact complex. A well-developed tumour vascular supply is required to ensure a sufficient delivery of glucose and oxygen to support the metabolism essential for tumour growth. However, an inadequate vascularisation of tumour will result in hypoxia, a factor that is known to stimulate anaerobic metabolism of glucose. Thus, the balance between tumour blood flow and metabolism will be an important indicator of the biological status of a tumour and hence the tumour's likely progression and response to treatment. This article reviews the molecular biology of tumour vascularisation and metabolism, relating these processes to currently available imaging techniques while summarising the imaging studies that have compared tumour blood flow and metabolism. The potential for vascular metabolic imaging to assess tumour aggression and sub-classify treatment response is highlighted.

Relationship Between 18F-FDG Accumulation and Lactate Dehydrogenase A Expression in Lung Adenocarcinomas

“…However, the underlying mechanism for elevated 18 F-FDG accumulation in malignant tumors is multifactorial and more complex than it may appear at first glance (15,27). This study shows that SUV max is significantly higher in high-LDHA-expression tumors than low-LDHA-expression tumors, indicating that, in lung adenocarcinomas, 18 F-FDG accumulation might reflect LDHA expression.…”

Quantitative Assessment of Breast Parenchymal Uptake on 18F-FDG PET/CT: Correlation with Age, Background Parenchymal Enhancement, and Amount of Fibroglandular Tissue on MRI

“…Similar to MRI, PET using the radiotracer 18 F-FDG provides insight into the physiologic activity of the normal breast parenchyma through the depiction of tissue glucose metabolism (19)(20)(21)(22)(23)(24). This 18 F-FDG uptake is defined as breast parenchymal uptake (BPU).…”

Predicting tumour response

“…Several studies have suggested that tumours with high glucose metabolism (and therefore high standardized uptake values with FDG-PET imaging) respond poorly to treatment and are associated with poorer prognosis [6264] . However, FDG uptake can also be increased in the absence of hypoxia and thus increased FDG uptake in the presence of hypoxia or low perfusion is more reflective of tumour adaption to hypoxia than measurements of FDG uptake alone [65] . Thorwarth et al [53] reported that the combined use of […”