Abstract
For several decades, cytotoxic chemotherapeutic agents were considered the basis of anticancer treatment for patients with metastatic tumors. A decrease in tumor burden, assessed by volumetric computed tomography and magnetic resonance imaging, according to the response evaluation criteria in solid tumors (RECIST), was considered as a radiological response to cytotoxic chemotherapies. In addition to RECIST-based dimensional measurements, a metabolic response to cytotoxic drugs can be assessed by positron emission tomography (PET) using 18F-fluoro-thymidine (FLT) as a radioactive tracer for drug-disrupted DNA synthesis. The decreased 18FLT-PET uptake is often seen concurrently with increased apparent diffusion coefficients by diffusion-weighted imaging due to chemotherapy-induced changes in tumor cellularity. Recently, the discovery of molecular origins of tumorogenesis led to the introduction of novel signal transduction inhibitors (STIs). STIs are targeted cytostatic agents; their effect is based on a specific biological inhibition with no immediate cell death. As such, tumor size is not anymore a sensitive end point for a treatment response to STIs; novel physiological imaging end points are desirable. For receptor tyrosine kinase inhibitors as well as modulators of the downstream signaling pathways, an almost immediate inhibition in glycolytic activity (the Warburg effect) and phospholipid turnover (the Kennedy pathway) has been seen by metabolic imaging in the first 24 h of treatment. The quantitative imaging end points by magnetic resonance spectroscopy and metabolic PET (including 18F-fluoro-deoxy-glucose, FDG, and total choline) provide an early treatment response to targeted STIs, before a reduction in tumor burden can be seen.
Highlights
The field of medical oncology has emerged in the 1950s when various chemotherapeutic drugs were used to control cancer cell growth by interfering with the cell cycle and DNA replication
Metabolic imaging – based on positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) – is suited for monitoring the treatment response to cytostatic signal transduction inhibitors (STIs) since the signal transduction pathways are directly linked to the aberrant metabolic phenotype exhibited in human malignancies [11,12,13,14,15,16]
FDG-PET/computed tomography (CT) is frequently acquired at the baseline for radiation treatment planning since high metabolic activity is regarded as a positive predictive factor for treatment response [70]
Summary
The field of medical oncology has emerged in the 1950s when various chemotherapeutic drugs were used to control cancer cell growth by interfering with the cell cycle and DNA replication. Advances in oncologic imaging pave the way for rapid optimization of personalized anticancer therapies through the non-invasive assessment of the mechanism of actions, efficacy and resistance development that improve clinical decision making for novel targeted agents beyond the traditional endpoints of morbidity and mortality. Metabolic imaging – based on positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) – is suited for monitoring the treatment response to cytostatic STIs since the signal transduction pathways are directly linked to the aberrant metabolic phenotype exhibited in human malignancies [11,12,13,14,15,16]. In the past 10 years, advances in hyperpolarized 13C-MRS allowed for non-invasive assessment of metabolic activities in glucose, lipid, and amino acid metabolism in tumorbearing animals and humans [22, 23]
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