title: Functional investigation of bone implant viability using radiotracers in a new model of osteonecrosis.
abstract: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected.
  Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis.
  Radiolabeling achieved high (>95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology.
  1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications.
authors.affiliation: Universidade Federal da Bahia, Faculdade de Medicina, Departamento de Ortopedia, Bahia/BA, Brazil.
authors.forename: Luis
authors.initials: L
authors.lastname: Schiper
authors.affiliation: Instituto de Energia e Pesquisa Nuclear, Centro de Radiofarmácia, São Paulo/SP, Brazil.
authors.forename: Bluma Linkowski
authors.initials: BL
authors.lastname: Faintuch
authors.affiliation: Universidade Federal da Bahia, Faculdade de Medicina, Departamento de Ortopedia, Bahia/BA, Brazil.
authors.forename: Roberto José da Silva
authors.initials: RJ
authors.lastname: Badaró
authors.affiliation: Instituto de Energia e Pesquisa Nuclear, Centro de Radiofarmácia, São Paulo/SP, Brazil.
authors.forename: Erica Aparecida de
authors.initials: EA
authors.lastname: Oliveira
authors.affiliation: Universidade de São Paulo, Faculdade de Odontologia, Departamento de Biomateriais e Biologia Oral, São Paulo/SP, Brazil.
authors.forename: Victor E Arana
authors.initials: VE
authors.lastname: Chavez
authors.affiliation: Universidade de São Paulo, Faculdade de Odontologia, Departamento de Biomateriais e Biologia Oral, São Paulo/SP, Brazil.
authors.forename: Elisangela
authors.initials: E
authors.lastname: Chinen
authors.affiliation: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Divisão de Cirurgia Gastrointestinal, São Paulo/SP, Brazil.
authors.forename: Joel
authors.initials: J
authors.lastname: Faintuch
mesh_terms: D000818:Animals; D016025:Bone Transplantation; D000069343:Bone-Implant Interface / Q000502:physiology*; D004164:Diphosphonates; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000473:pathology / Q000503:physiopathology; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology; D015609:Organotechnetium Compounds; D010020:Osteonecrosis / Q000473:pathology / Q000503:physiopathology*; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D013997:Time Factors; D014022:Tissue Survival / Q000502:physiology; D014057:Tomography, X-Ray Computed
chemical_list: D004164:Diphosphonates; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C582442:technetium 99m HYNIC-E(c(RGDfK))2; C027474:methylene diphosphonate