Clinical operation at the Austin Hospital Centre for PET in Melbourne commenced in 1992 with 20 scans per month. After the initial few years of operation needed to develop and validate appropriate protocols and procedures, the patient throughput has gradually increased to nearly 1,000 scans per year in 1998 as clinical applications of PET in areas such as Cardiology, Neurology and Oncology continue to grow. With now up to nine radiotracers and radiopharmaceuticals routinely produced in the Centre, various relevant clinical parameters can be assessed including glucose metabolism, hypoxia, blood flow and neuroreceptor mapping. These are explained in detail below.
-
Glucose metabolism
Since its development 18FDG has become the most widely used radiopharmaceutical in the PET clinic. 18FDG uptake in biological tissue reflects glucose metabolism and could be used as a marker of cell dysfunction. To date, the clinical usage of 18FDG at the Austin Hospital Centre for PET has been concentrated in the following areas:
i) oncology: to characterise various tumours and enable the effects of therapy to be monitored. A correlation has been found between the glucose accumulation by tumour and the degree of malignancy.
ii) epilepsy: to help in the selection of patients for surgical treatment of epilepsy. In three-quarters of patients with complex partial seizures, epileptogenic tissue has been identified as an area of hypometabolism.
iii) cardiology: to identify patients likely to benefit from myocardial revascularisation. Ischaemic myocardium maintains its viability by increasing glycolytic flux rate, resulting in an 18FDG tissue accumulation.
-
Hypoxic tissue visualisation
A nitroimidazole derivative, 18F-Fluoromisonidazole (18FMISO), is a relatively new tracer able to selectively identify viable hypoxic tissue by metabolic trapping in viable cells with reduced oxygen. To date, the initial clinical usage of 18FMISO at the Austin Hospital Centre for PET has been concentrated in two pilot studies:
i) oncology: to gain an understanding of hypoxia within brain tumours. It has been suggested that reduced oxygen within tumours may be a factor in resistance to standard radiotherapy and chemotherapy.
ii) neurology: to identify tissues likely to represent the ischaemic penumbra in patients after acute ischaemic stroke. These findings may have important implications for the therapeutic window after stroke.
-
Oxygen metabolism and blood flow
The function of the cerebral tissue depends critically on the use of oxygen and impairment in its rate of consumption often constitutes a pathological condition. The PET method represents a potentially valuable tool for the estimation of physiological parameters such as oxygen metabolic rate and cerebral blood flow. In addition, the short half-life of oxygen-15 (t½=2.1 min) allows for rapid sequential studies of cerebral blood flow using H215O (PET activation studies). To date the initial usage of 15O2, C15O2 and H215O at the Austin Hospital Centre for PET has been concentrated on research protocols:
i) neurology: to help in predicting outcomes and patient management after ischemic stroke. Using 15O2 and H215O with PET, oxygen consumption and cerebral perfusion can be quantitatively measured in ischaemic stroke.
ii) neuroscience: to advance in the quantification of brain function such as lexical decision making, visual processing, parietal lobe function and working memory processing.
In addition, PET studies using radiotracers such as 13N-ammonia allow for qualitative and quantitative regional coronary blood flow evaluation in coronary artery disease.
-
Receptor mapping
Several neurological and psychiatric diseases have been related to neurotransmitter and receptor disorders. There now exist PET radiotracers for mapping and quantifying many neuroreceptors including the dopamine receptor, the serotonin receptor and the benzodiazepine receptor. Through PET studies, it is possible to relate changes in neurotransmitter function to clinical features. To date, at the Austin Hospital Centre for PET, 11C-flumazenil has been used to quantify the number and affinity of cerebral benzodiazepine receptors in the pathogenesis of various psychiatric disorders such as post-traumatic stress disorder (PTSD) and panic disorder. There is widespread therapeutic use of benzodiazepines for their pharmacological actions such as anxiolitic, anticonvulsant and sedative-hypnotic effects. The actions of the benzodiazepines are thought to be caused by enhancing the effects of GABA-mediated inhibition in the central nervous system.
|
|
