There are many exciting areas of research associated with Tc that are open to further exploration. These span from basic coordination chemistry, through radiochemistry and radiopharmacy research, to radiopharmaceutical development. Advances in these areas will require contributions from not only inorganic and radiopharmaceutical chemists but also scientists with a broader set of skills including those having expertise in organic chemistry and drug discovery, imaging physics and biology/biochemistry.
Modern drug discovery techniques, which are revolutionizing pharmaceutical research, are only just beginning to have an impact on Tc-radiopharmaceutical chemistry. The number of Tc radiopharmaceuticals approved lately is disappointing when compared to the amount of effort being put into developing new agents.96 In order to discover new Tc radiopharmaceuticals in a time- and resource-efficient manner it is essential that new methods for library construction, for systems beyond simply peptides, be developed. Furthermore, high throughput screening systems must be developed which allow these libraries to be rapidly evaluated for those factors that are relevant to radiopharmaceu-tical development.
One of the key steps to achieving the above-stated goal is the continuing exploration of the fundamental coordination and radiochemistry of Tc. The potential impact of new Tc chemistry is illustrated by the effect that the development of the Tc(CO)^ synthon is having on modern Tc radiopharma-ceutical chemistry. This particular core, amongst other things, enables solidphase synthetic procedures to be performed, which were not possible with preexisting Tc synthons. New cores will similarly open new avenues for radio-pharmaceutical development.
Another area for future research is in combining the diagnostic power of technetium with the therapeutic capability of other radioisotopes. Technetium's congener, Re, has two isotopes (186Re and 188Re) which are available commercially and which can be used to create radiotherapy agents. There is an oft-cited avowal that Tc and Re can be considered a 'matched pair' for imaging and therapy, the idea being that the Tc complex can be used for detecting and staging diseases like cancer while the Re complex, which would in theory posses the same biodistribution profile, would then be used for therapy. Unfortunately the stability of 186/188Re complexes is often much less than the 99mTc analogue meaning that the biodistribution profiles are in fact often different. New ligands which are capable of preventing premature decomposition of radio-rhenium complexes is a major obstacle to making the matched-pair dream a reality.
An additional area that deserves special notation is the use of animal imaging.97 Scanners that are dedicated for animal imaging are now available for both PET98,99 and SPECT.100,101 These instruments afford the opportunity to obtain images of animal models at a higher resolution than with the counterparts designed for humans. Furthermore, researchers who have animal scanners are capable of performing multiple imaging studies in the same animal, which increases the accuracy of experiments, without being encumbered by clinical demands on an instrument.
As the pharmaceutical industry continues to recognize the importance of molecular and animal imaging in drug development,102,103 99mTc-labeled compounds will begin to play an important role in drug development and testing. With the ability to incorporate Tc into peptides that target specific receptors, it is conceivable that in the future, lead pharmaceutical candidates identified from large in vitro screening studies will subsequently be evaluated for their ability to displace receptor-specific Tc ligands in vivo. Screening in vivo offers a means of evaluating compounds in a more realistic environment than is presently offered by screens involving isolated cells or receptors.
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