Synthesis, Characterization and Biodistribution Studies of 125I-Radioiodinated di-PEGylated Bone Targeting Salmon Calcitonin Analogue in Healthy Rats
MetadataShow full item record
Purpose: The objective of this study was to prepare a bisphosphonate (BP) mediated bone targeting di-PEGylated salmon calcitonin analogue sCT-2(PEG-BP) as a novel bone targeting pharmaceutical. Methods: HPLC was used for isolation of sCT-2(PEG-BP) from the reaction mixture, followed by determination of possible PEGylation sites by trypsin digestion. Stability of the compound over time, bone mineral affinity using hydroxyapatite, and biodistribution in normal rats after radiolabeling of sCT-2(PEG-BP) or control sCT with 125I was evaluated. Results: PEGylated sCT analogues were synthesized, and sCT-2(PEG-BP) was isolated by HPLC and confirmed by MALDI-TOF and ICP-MS. MALDI-TOF analysis of trypsinized fragments suggested Cys1 (or Lys11) and Lys18 to be the two PEGylation sites. Bone mineral affinity test showed sCT-2(PEG-BP) or 125I-sCT-2(PEG-BP) exhibited significantly increased bone mineral affinity over sCT or 125I-sCT, respectively. sCT-2(PEG-BP) remained stable for at least 1 month. In vivo biodistribution study showed significantly increased bone retention and prolonged plasma circulation time for sCT-2(PEG-BP) compared to the control sCT. Conclusion: Those results support sCT-2(PEG-BP) as a promising new drug candidate for the treatment of resorptive and/or maladaptive bone conditions, such as Osteoporosis, Osteoarthritis, Rheumatoid Arthritis, Paget’s disease and bone cancers.
Showing items related by title, author, creator and subject.
Analysis of candidate genes within the 3p14-p22 region of the human genome for association with bone mineral density phenotypesMullin, Benjamin H (2011)Previous studies have identified the 3p14-p22 chromosomal region as a quantitative trait locus for bone mineral density (BMD). The overall aim of this thesis is to identify the gene or genes from this region that are ...
Jefferson, Amanda; Fyfe, Sue; Downs, Jennepher; Woodhead, H.; Jacoby, P.; Leonard, H. (2015)Bone mass and density are low in females with Rett syndrome. This study used Dual energy x-ray absorptiometry to measure annual changes in z-scores for areal bone mineral density (aBMD) and bone mineral content (BMC) in ...
A two-year history of high bone loading physical activity attenuates ethnic differences in bone strength and geometry in pre-/early pubertal children from a low-middle income countryMeiring, R.; Avidon, I.; Norris, S.; McVeigh, Joanne (2013)We examined the interplay between ethnicity and weight-bearing physical activity on the content and volumetric properties of bone in a pre- to early pubertal South African Black and White population. Sixty six children ...