Abstract
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Objectives Advancements associated with the production and purification of 68Ga has primed it for an entrance to routine clinical application. The clinical environment favours simple labelling protocols, such as that of 99mTc radiopharmaceuticals, something which is not possible with currently used 68Ga chelators. A similar format is required for 68Ga to make a significant impact, and requires chelators which can be labelled quatitatively and quickly under exceptionally mild conditions. At SNMMI 2013 we showcased the DATA chelators which facilitate quantitative complexation of 68Ga under very mild conditions (60 MBq 68Ga pH 4-7, 25°C, 10 μM, < 5 min), comparing favourably with the current state of the art. As a result these chelators are promising candidates for use in kit-type labelling and 68Ga-PET in general. Furthermore, their ability to radiolabel at 25°C and over wide pH range presents the opportunity to label previously inaccessible temperature/pH sensitive targeting vectors (TV's). In their original form the DATA chelators cannot be coupled to TV's to give bifunctional chelators (BFC's). The objective has been to develop BFC’s based on these parent structures, and do preliminary investigations into the development of kit-type labelling setups.
Methods Three preferred points of conjugation were selected based on previous experience. Chelators were functionalised to facilitate attachment of bisphosphonate and octreotate TV’s. Conventional and resin based kit-type labelling have been evaluated for the DATAm chelator.
Results Numerous synthetic pathways have been investigated, resulting in three novel functionalised DATA chelators. These functionalised chelators display labelling chacateristics similiar to those of the orginal DATA chelators. Conventional and resin based kit-type labelling afforded only the desired radiolabelled product in < 10 min at 25°C.
Conclusions Preliminary work towards kit-type labelling have produced promising results, and will be evlauated on a BFC. Ongoing research involves the development and evaluation of BFC's, with focus on bisphosphonate derivatives for imaging bone metastases.