[HTML][HTML] Novel radiolabeled bisphosphonates for PET diagnosis and endoradiotherapy of bone metastases

N Pfannkuchen, M Meckel, R Bergmann, M Bachmann… - Pharmaceuticals, 2017 - mdpi.com
N Pfannkuchen, M Meckel, R Bergmann, M Bachmann, C Bal, M Sathekge, W Mohnike…
Pharmaceuticals, 2017mdpi.com
Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are
characterized by an increased bone turnover, which can be visualized by positron emission
tomography (PET), as well as single-photon emission computed tomography (SPECT).
Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast
to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an
analog to the established 99mTc generator exists. Complexation of Ga (III) requires the use …
Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are often used. The combination of these macrocyclic chelators and bisphosphonates is currently studied worldwide. The use of DOTA offers the possibility of a therapeutic application by complexing the β-emitter 177Lu. This overview describes the possibility of diagnosing bone metastases using [68Ga]Ga-BPAMD (68Ga-labeled (4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid) as well as the successful application of [177Lu]Lu-BPAMD for therapy and the development of new diagnostic and therapeutic tools based on this structure. Improvements concerning both the chelator and the bisphosphonate structure are illustrated providing new 68Ga- and 177Lu-labeled bisphosphonates offering improved pharmacological properties.
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