The Future

With increasing experience, interpretation of lymphoscintigrams should become more reliable. For instance, more abnormal drainage patterns will be described in the future [69]. That means that fewer sentinel nodes will go unnoticed by the nuclear medicine physician and the surgeon. Both the strong and weak points of lymphoscintigraphy will become better defined. Because the resolution of gamma cameras is not likely to improve dramatically in the foreseeable future, advances in lymphoscintigraphy will have to come from use of better tracers. What should we be working on to develop better tracers? A typical radiopharmaceutical consists of a radionuclide that emits the radiation that is used for imaging and a second part that determines the biological properties of the molecule. 99mTc comes close to the ideal radionuclide. It is easy to obtain and to handle in the radiophar-macy laboratory. It emits gamma rays with an energy of 140 keV, particularly suitable for present-day gamma cameras. It has a physical half-life of 6.2 h, long enough for the purposes of lymphoscintigraphy and next-day gamma probe detection, but short enough for contamination, should that happen, to be of a limited duration.

What about the other part that makes up the tracer molecule? What are the properties of the ideal tracer for lymphatic mapping of cutaneous lesions? The ideal tracer is easy to prepare in the radiopharmacy laboratory and remains stable. After administration into the interstitium, it is accumulated in the lymphatic sys tem and travels to the first lymph node. Ideally, within a few hours there should be no residual activity at the injection site. Complete clearance eliminates the problem of remaining radioactivity at a nearby injection site obscuring a sentinel node. The ideal tracer is avidly accumulated and retained in the first node without some of it passing through and moving on to subsequent nodes: a radioactive node is a sentinel node. This obviates the need for dynamic imaging and also eliminates the need for the surgeon to use the blue dye technique. The radiation dose to the patient and hospital personnel is low and there are no other side effects.

Because macrophages have such a great affinity for the protein derivatives that are currently used, it seems logical to take advantage of this fact. Modifications of the shape of the particles or their surface characteristics may improve clearance from the injection site and may make them more appetizing for macrophages [77]. Different protein products with varying size particles also need to be investigated. In the groin, additional (second-tier) nodes are depicted more often than in the axilla. Therefore, it may well be that we will use different tracers for different lymphatic fields in the near future. However, within a few years there may be nonparticulate tracers that are accumulated in a lymph node through other mechanisms. 99mTc-labeled polydiethylenetriamine pentaacetic acid poly-mannosyl polylysine (DTPA-maK-PL) may be a step in that direction [78]. An animal experiment showed that this tracer is irreversibly bound to lymphocytes through a receptor-specific interaction. What about tracers that are targeted directly against tumor cells? Will there be tumor-seeking agents that accumulate in lymph nodes with metastatic disease while leaving healthy nodes alone? Such a tracer could be injected either at the tumor site or even into the bloodstream. The surgeon could then remove all radioactive nodes (and visceral metastases for that matter) and be sure to have cured the patient. If no nodes light up, there would be no need to explore the lymphatic field. The problem with this train of thought is that there must be a certain amount of radioactivity in a cancer deposit for it to be detected. That means that such a deposit must have a certain size. That size is currently 3 mm with the best available tracer and the tumor cell type that has the highest avidity for that agent. Monoclonal antibodies against tumor-specific antigens have potential in this respect. However, although the specificity of monoclonal antibodies may be 100%, what is lacking are truly tumor-specific antigens that are consistently present in various tumor subtypes. These antigens need to be tumor-specific, distributed uniformly among tumor cells with a high density, and must be accessible to the antibody that is used. Clinical diagnosis with labeled antibodies has had limited value until now because tumor deposits smaller than 3 mm cannot be detected and such micrometastases need to be identified because they may ultimately kill the patient. Far smaller tumor deposits can be detected with current pathological techniques. This also rules out scintigraphy with agents like thallium-201 [79], 99mTc sestamibi [80], iodine-123 iodobenza-

mide [81], and indium-111 pentetreotide [81] to name but a few, and also other techniques like ultrasonography for staging and positron emission tomography (PET) [82-84]. Although PET with 2-fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is a highly sensitive technique for detecting metastatic melanoma, it cannot detect metastases smaller than approximately 5 mm [85,86]. So, these tracers and these techniques will not replace (the tracers currently used in) lymphatic mapping, but they may play a future role in identifying patients with metastases 3-10 mm in size that cannot be detected by physical examination. Such patients can then be spared a sentinel node biopsy before a formal regional node dissection. Lymphatic mapping and a more detailed examination of the sentinel lymph node can identify micrometastatic disease with a sensitivity of being able to identify a single melanoma cell in a background of a million lymphocytes. There will not be a PET scan, MRI, or CT scan that has that kind of sensitivity.

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Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.

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