Functional investigation of bone implant viability using radiotracers in a new model of osteonecrosis |
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| Authors: | Luis Schiper Bluma Linkowski Faintuch Roberto José da Silva Badaró Erica Aparecida de Oliveira Victor E Arana Chavez Elisangela Chinen Joel Faintuch |
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| Institution: | 9. Universidade Federal da Bahia, Faculdade de Medicina, Departamento de Ortopedia, Bahia/BA, Brazil;99. Instituto de Energia e Pesquisa Nuclear, Centro de Radiofarmácia, São Paulo/SP, Brazil;999. Universidade de São Paulo, Faculdade de Odontologia, Departamento de Biomateriais e Biologia Oral, São Paulo/SP, Brazil;9V. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Divisão de Cirurgia Gastrointestinal, São Paulo/SP, Brazil |
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| Abstract: | OBJECTIVES: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.METHODS: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.RESULTS: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.CONCLUSIONS: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. |
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| Keywords: | Osteonecrosis Angiogenesis Femur Abdominal Pocket Radiotracers Technetium-99m Experimental Model |
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