%0 Journal Article
%T Bone-seeking TRAP conjugates: surprising observations and their implications on the development of gallium-68-labeled bisphosphonates
%A Johannes Notni
%A Jan Plutnar
%A Hans-J¨¹rgen Wester
%J EJNMMI Research
%D 2012
%I Springer
%R 10.1186/2191-219x-2-13
%X Two trimeric bisphosphonate conjugates of the triazacyclononane-phosphinate (TRAP) chelator were synthesized, labeled with Ga-68, and used for microPET imaging of bone in male Lewis rats. Both Ga-68 tracers show bone uptake and, thus, are suitable for PET bone imaging. Surprisingly, Ga-71 nuclear magnetic resonance data prove that Ga(III) is not located in the chelating cavity of TRAP and must therefore be bound by the conjugated bisphosphonate units.The intrinsic Ga-68 chelating properties of TRAP are not needed for Ga-68 PET bone imaging with TRAP-bisphosphonate conjugates. Here, TRAP serves only as a trimeric scaffold. For preparation of Ga-68-based bone seekers for PET, it appears sufficient to equip branched scaffolds with multiple bisphosphonate units, which serve both Ga-68-binding and bone-targeting purposes.Geminal bisphosphonates possess strong affinity to bone [1,2]. In living organisms, administration of bisphosphonates leads to inhibition of osteoclasts (bone resorbing cells), which results in a lower rate of bone resorption [3,4]. Therapy with bisphosphonate drugs is thus performed to prevent decrease of bone density caused by osteogenesis imperfecta (brittle bone disease) [5] or osteoporosis [3,6]. In addition, bisphosphonate complexes of 99mTc (e.g., of medronic acid, '99mTc-MDP'; see Figure 1) are the mainstay of bone imaging by scintigraphy and SPECT. However, as positron emission tomography (PET) offers higher resolution and sensitivity, PET bone-imaging agents are of high interest. Direct utilization of the ¦Â+-emitting radionuclide 18 F (t1/2 = 110 min, Emax,¦Â+ = 634 keV) is the most simple and straightforward approach because [18 F]fluoride 18 F- inherently possesses a high affinity to bone. However, 18 F is cyclotron-produced, and therefore, a full geographical coverage, comparable to the supply of generator-produced 99mTc, cannot be guaranteed. Thus, bisphosphonate mono-conjugates of the currently most popular radiometal chelators 1,4,7,10-tet
%K Gallium-68
%K Bisphosphonates
%K Positron emission tomography
%K Bone seekers
%K MicroPET
%K Bone imaging
%U http://www.ejnmmires.com/content/2/1/13