Peroperative nuclear medicine

Tumours identified clinically or by external imaging frequently require surgical treatment. The effectiveness of such treatment is invariably dependent upon the complete excision of all tumour tissue. Microscopic and occult disease not readily seen by the surgeon may remain in situ, ultimately leading to the patient's demise. Despite the use of state-of-the-art imaging there are many instances where the surgeon may benefit from additional information as to the location and extent of diseased tissue. Radiopharmaceutical compounds have been used with great success for the detection of tumour tissue. The use of radiolabelled antibodies has led to recent increased interest in the peroperative technique [1 8]. However, the use of sterilizable probes for intraoperative detection of tumours is far from new. The first known studies were published by Selverstone et al. in 1949 [9], who used 30 150 MBq ~2p buffered sodium phosphate for the localization of brain tumours. Detection of the fl-emission was achieved using cylindrical GM tubes of 3 and 5 mm diameter made in the form of ventricular needles, which were sterilized in formalin prior to surgery. Other studies performed in the 1950s used surgical probe detectors for ocular melanoma and GI tumours [10, 11]. The first peroperative use of current radiation detector technology, the CsI(T1) detector with a light guide, was published in 1956 by Harris et al. [12] using aalI for the detection of recurrent thyroid tumours. More recently, solid-state detectors have been used for intraoperative studies [13-15]. The main intraoperative application to be accepted as standard surgical practice has been in the localization of osteoid osteoma [16]. This benign bony tumour occurs predominantly in adolescents. Patients experience intense pain at night, causing not only extreme discomfort to the patient but much anxiety on the part of parents of young children. Symptoms may be relieved with analgesics, but surgery is the only solution and, if successful, provides a permanent cure. Since osteoid osteomas concentrate the conventional 99mTc bone imaging radiopharmaceuticals, they may be successfully localized using a suitable probe at operation. The paper by Kircher et al. in this tissue [17] demonstrates the reliability of the procedure after follow-up in 12 cases. The proven benefit to both the patient and surgeon is not only in the accurate delineation of the tumour, but also in knowing when the nidus has been successfully removed, thus sparing normal bone tissue, which is especially important in the weight-bearing long bones. Peroperative nuclear medicine procedures offer potential in the localization of a range of tumour types utilizing conventional radiopharmaceuticals (see Table 1). In addition, surgical probes have been used for detecting accessory spleen, sites of gastrointestinal bleeding, focal areas of myocardial damage, sites of plutonium deposition and a lost brachytherapy seed. A comprehensive review article by Woolfenden and Barber [18] outlines the development of probe systems and their application in surgery. The optimization of the peroperative technique still leaves much room for investigation, with the choice of radionuclide and the design of intraoperative probes being the two critical factors affecting the performance of the technique. For accurate localization it is desirable that low-energy radionuclides are employed [1-3, 19]. The use of highenergy radionuclides reduces the specificity of the procedure since problems arise from scattered radiation from sites of high normal uptake of tracer, such as the liver [3]. The use of radionuclides having high gamma energies also places a requirement on increased shielding around the detector element, making the probe heavy and bulky, thereby reducing its acceptability to the surgeon. This therefore eliminates the routine use of lalI and 11 ~In, which have commonly been used for radiolabelling antibodies. Reports of radioimmunoguided surgery utilizing ~ ~ tin have concluded that the routine use of lower-energy radionuclides would be preferablein addition to more specific antibodies with higher tumour to normal tissue uptake [3, 7], The use of 12~I for radioimmunoguided surgery (RIGS) appeared to be attractive from a physical point of view [1, 2, 19], but would appear to be contraindicated for routine use because of the high patient radiation-absorbed dose [3]. Regulatory authorities in at least one European state have refused permission for the use ~25I for routine use in RIGS. Radionuclides such as 99mTc and 12aI with their relatively low gamma energies would seem eminently suitable for intraoperative use. A number of surgical probe systems coupled to scalerratemeters are now commercially available (Table 2). Some are designed for general use while others have been produced for specific procedures, such as with radiolabelled antibodies (Oncoprobe and Neoprobe). The