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Prostate cancer is the third most common deadly disease and the most common cancer in industrialized countries. Since prostate cancer is a slow-growing tumor, early diagnosis can significantly increase life expectancy. However, late stage diagnosis is often fatal as it typically affects other organs. There are several methods available for early diagnosis, the most important of which is the determination of the PSA level. Nevertheless, nuclear medicine concepts have been further developed in ...Prostate cancer is the third most common deadly disease and the most common cancer in industrialized countries. Since prostate cancer is a slow-growing tumor, early diagnosis can significantly increase life expectancy. However, late stage diagnosis is often fatal as it typically affects other organs. There are several methods available for early diagnosis, the most important of which is the determination of the PSA level. Nevertheless, nuclear medicine concepts have been further developed in recent years. For example, prostate cancer can be reliably diagnosed by positron-emisson tomography. So-called tracers labeled with a radioactive nuclide are used for this purpose. The most important representatives for the visualization of prostate carcinomas are [68Ga]Ga-PSMA-11 and [68Ga]Ga-PSMA-617. In addition, PSMA-617 can also be used therapeutically. Even though these derivatives are already clinically established and routinely used, they have some disadvantages such as high accumulations in other organs or complex syntheses. Therefore, the demand for molecules that are more flexible and offer a better biodistribution is still high. In this context, squaric acid coupled KuE derivatives have proven to be promising. They show an improved biodistribution as the accumulations of gallium complexes in liver and kidney is significantly reduced compared to PSMA-11 and PSMA-617. Extensive in vivo studies have been performed and besides the most promising derivatives DOTAGA.SA.PSMA also TRAM.SA.PSMA and NODAGA.SA.PSMA have been investigated. Furthermore, there is a great demand in this field for molecules that can be used with versatile nuclides. Even though PSMA-617 including a DOTA chelator is very flexible in terms of nuclide selection, this derivative can usually only be labelled at elevated temperatures, which makes "kit application" considerably more difficult. Promissing alternatives are the hybrid chelates DATA and AAZTA. These were also equipped with an SA.PSMA unit within the context of this work and AAZTA.SA.PSMA was investigated regarding its labeling properties with 44Sc, 68Ga and 177Lu. Another interesting metal for use in radiopharmaceutical applications is copper. There is a broad variety of isotopes that can be applied for diagnostic (64Cu) as well as for therapeutic purposes (64Cu/67Cu) and would allow for easier dosimetric investigations. In this context both AAZTA5OMe and DATA5mOMe as well as the already mentioned derivative AAZTA.SA.PSMA were investigated with regard to 64Cu. It was found that the labelling can be completed quickly and with good radiochemical yields, but that the in vitro stability in human serum over a period of 24 hours is too low, especially with regard to therapeutic use.» weiterlesen» einklappen

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DDC Sachgruppe:
Chemie