Bifunctional bisphosphonate complexes for the diagnosis and therapy of bone metastases

Abstract

Easily synthesised and structurally well-defined novel imaging/therapeutic radiopharmaceutical agents for bone metastases are described.

NF-κB as a Therapeutic Target in Inflammatory-Associated Bone Diseases

“…Therefore, the concept of bone-targeted delivery system is the use of biomolecules conjugated with bisphosphonates as ligands targeting bone mineral (Cole, Vargo-Gogola, & Roeder, 2016). Clinical applications investigating bisphosphonates as a targeting ligand include metabolic bone diseases such as osteoporosis (Bhandari, Newa, Chapman, & Doschak, 2012; Fujisaki et al, 1997; Morioka et al, 2010), bone infection (Houghton et al, 2008), rheumatoid arthritis (Hirabayashi et al, 2001), osteosarcoma, and cancer metastases to bone (Klenner et al, 1990; Reinholz et al, 2010; Torres Martin de Rosales, Finucane, Mather, & Blower, 2009). Intravenous injection or oral administration of bisphosphonate-conjugated vehicle delivered the desired compounds to bone due to their high affinity for calcium crystals (Widler, Jahnke, & Green, 2012).…”

Preparation, 99mTc-labeling and biodistribution studies of a PNA oligomer containing a new ligand derivative of 2,2′-dipicolylamine

“…Furthermore, this ligand needed to contain a functional group to allow its coupling to a PNA oligomer. Our attention rapidly turned to 2,2′-Dipicolylamine (Dpa) derivatives, which have already been intensively used in nuclear chemistry and which can be furthermore easily functionalized [53][54][55][56][57][58][59][60][61][62][63][64][65][66]. Thus, the ligand 2-azido-N,N-bis((pyridin-2-yl)methyl)ethanamine (Dpa-N 3 , Scheme 1) was prepared in a one-step synthesis starting from the known compound 2-(bis(pyridin-2-ylmethyl)amino)ethanol [51] (Dpa-OH) with triphenyl phosphine, diisopropyl azodicarboxylate and diphenylphosphoryl azide in THF (Scheme 1).…”

Synthesis, Characterization, and Application of Core–Shell Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm) Nanoparticle as Trimodal (MRI, PET/SPECT, and Optical) Imaging Agents

“…8,20,21,33 Both Co 0.16 Fe 2.84 O 4 @NaYF 4 (Yb, Er)-BP-PEG and Fe 3 O 4 @NaYF 4 (Yb, Tm)-BP-PEG particles showed a high affinity to 99m Tc-DPA-ale (data not shown) and 64 Cu-(DTCBP) 2 , which has two uncoordinated bisphosphonate groups, 8,20 with up to 96% labeling efficiency (Table S5). The ability to bind readily with [ 18 F]-fluoride and bisphosphonate conjugates of 64 Cu and 99m Tc offers potential applications in PET and SPECT imaging.…”

“…9,11 The majority of current multimodality contrast agents are based on superparamagnetic iron oxide NPs, 12−14 while a few examples of Gd 15,16 or Mn 17 containing NPs have also been reported. Since Weissleder et al 18 reported their pioneering work on multimodal imaging, combinations of NPs and functional polymers 19 or polydentate ligands 8,20,21 have been widely applied to obtain multifunctional agents. 14,15 An alternative approach is hybrid inorganic nanocomposites containing two materials with different properties, such as Fe 3 O 4 @NaGdF 4 NPs, 22 NaYF 4 @Fe x O y , 23 and Fe 3 O 4 @LnF 3 .…”