Del sujeto antiguo al sujeto moderno en relación con el cuidado de sí

i) E ^erim ental research

1. As with any radionuclide tracer technique, PET will evolve as the tracers available develop. A number of new tracers with clinical potential will and are being developed. One or more of the labelled thymidines presently being developed offers such promise.

2. The subject o f subclinical treatment response for chemotherapy and

radiotherapy is not addressed in this thesis because the focus of this study is PET for detection and staging of CRC. The use of PET for treatment monitoring should form the basis o f an investigation in its own right. The major impact on clinical practice will be that those who may not respond or who start treatment and are not benefiting in terms of tumour regression can be switched to alternative treatments or be spared the morbidity.

3. The study o f new pharmacological agents may now be studied in vivo using animal micro-PET cameras. This has particularly important implications for novel oncological agents especially those directed at cell signalling pathways or gene therapy. The prospect of molecular imaging is therefore a practical reality.

ii) Clinical issues

4. PET is an expensive modality with high start up costs needed to establish tracer production and distribution, purchase hardware and software and train staff. There are approximately 200 PET systems in chnical use in the United States where state-of-the-art PET systems cost $800,000 to $2.5 million. In

the UK, PET systems cost between £1-1.5 million. The overall cost o f a whole body FDG-PET is approximately £800 per study, of which £350 is spent on a single dose of FDG. The cost o f a spiral CT of the abdomen and pelvis is £350. There is a body of evidence established for the use of FDG-PET in the assessment of recurrent CRC mainly because FDG-PET leads to alteration in clinical management [Lai et al., 1996;Delbeke et al., 1997;Valk et al., 1999], for example surgery can be avoided due to the identification of non-resectable tumour. Valk et al [Valk et al., 1996] studied patients with lung cancer (99 patients), recurrent CRC (57), melanoma (36), and head and neck cancer (29) and found that the savings from contraindicated surgical procedures exceed the cost of PET by ratios of 2:1 to 4:1 depending on the indication. This same group also studied 115 patients with recurrent CRC and showed that the potential saving from the demonstration of non-resectable tumour by PET was approximately $3000 per preoperative study [Valk et al., 1999;Valk et al., 1996]. These studies demonstrate significant cost savings similar to those seen for FDG-PET used to assess solitary lung nodules [Gambhir et al., 1998] and must be considered when looking at the true cost of PET. Analytical cost modelling is now essential if clinical implementaion of PET is to take place.

5. Significant progress is to be expected with PET and other cross-sectional imaging modalities. Instrumentation is developing and multimodality

imaging, using a single instrument, is a reality with CT and/or MR combined PET scanners and PET capable gamma cameras coming onto the market. The aim is to increase the accuracy of image registration, between cross-sectional imaging modalities, which offer detailed anatomical information (CT/MR) and fimctional imaging techniques (PET), which offer metabolic information.

The quality of this detector technology comes at a price. The production cost is approximately 50% of the total cost and efforts by the manufacturers are concentrated on lowering these. By removing two thirds of the detector ring, the cost is reduced by 50%, but the sensitivity is also reduced to around to 80%. These rotating partial ring EGO PET detectors are practical alternatives to the full ring, multicrystal EGO PET.

6. Another development that is a compromise of the best that BGO PET has to offer is a change in detector design. Photo-multiplier-quadrant sharing and a convertible geometry combine to give a system which is flexible. There are gaps in the BGO detector ring, which reduces cost at the expense of overall sensitivity. However, when applied to image small objects the field of view can be shrunk using the convertible geometry, thus bringing the detectors together. This camera now acts as a full ring system and has increased detection sensitivity. This property is conversely lost when imaging bigger objects. Resolution o f a prototype camera is around 3mm.

7. Advances in detector materials continue also. A combined SPECT/PET camera has been developed using lutetium orthosilicate (LSO) crystals for coincidence imaging that are positioned behind Nal (T l) crystals for SPECT. This combined detector has a much higher sensitivity for 51 IKeV photons and it combines features of the photomultiplier quadrant sharing technology, which further reduces cost. In addition LSO can count six times faster than Nal (Tl).

These developments illustrate the drive from industry as well as clinicians to improve the instrumentation available. A realistic target for practical image resolution is 3mm and this is achievable. Experimental cameras designed for animal imaging have demonstrated resolution o f 1.5 to 2mm using tracers.

From the outset the primary objective has been to evaluate functional imaging against morphological techniques in CRC. The findings suggest that even though some drawbacks exist with PET, there is a case for incorporating this modality in certain applications for imaging CRC. This applies to the technology currently available to the clinician and the prospect of future developments heralds a most formidable clinical imaging tool. The major philosophical shift for the oncologist, both surgical and medical is to incorporate metabolic data from the CRC being studied to other clinical and imaging parameters. FDG-PET augments the information from conventional modalities and can be ^ p lie d in practical terms for the benefit of patients.