title: Bone-seeking TRAP conjugates: surprising observations and their implications on the development of gallium-68-labeled bisphosphonates.
abstract: BACKGROUND
  Bisphosphonates possess strong affinity to bone. 99mTc bisphosphonate complexes are widely used for bone scintigraphy. For positron emission tomography (PET) bone imaging, Ga-68-based PET tracers based on bisphosphonates are highly desirable.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meissner-Str, 3, Garching 85748, Germany. johannes.notni@tum.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Notni
authors.forename: Jan
authors.initials: J
authors.lastname: Plutnar
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester