64Cu-RGD and microPET/CT as an imaging biomarker for osteoclast number in mouse models of negative and positive osteoclast regulation

Objectives The goal of this study was to validate ⁶⁴Cu-CB-TE2A-c(RGDyK) (⁶⁴Cu-RGD) as a biomarker for osteoclast number. A change in osteoclast number was monitored by biodistribution and microPET imaging with CT in mice treated with osteoprotegerin (OPG) and Receptor Activator for Nuclear Factor κ B Ligand (RANKL). OPG is a negative regulator of osteoclasts and should decrease osteoclast number. RANKL is a positive regulator of osteoclast differentiation and leads to an increase in osteoclast number.

Methods C57BL/6 mice were treated with OPG at 0.2, 1.0 and 5.0 mg/kg twice a week for two weeks or with RANKL at 0.1 and 0.3 mg/kg twice a day for 10 days. On day 15 (OPG) or day 11 (RANKL) treated and control mice were injected with ⁶⁴Cu-RGD followed by PET imaging and biodistribution. Standard uptake values (SUVs) were determined. Bones were collected for histology.

Results Mice treated with 5 mg/kg of OPG or 0.3 mg/kg of RANKL showed a significant difference compared to control. The normal tissue biodistribution of the tracer did not vary greatly between the control and treated mice. PET images of animals treated with 0.3 mg/kg RANKL demonstrated significantly increased SUVs as compared to the control group. Histology and TRAP5b levels supported the biodistribution, PET, and TRAP5b data.

Conclusions Analysis of the PET images showed that ⁶⁴Cu-RGD bone uptake correlated with the osteoclast number and could be quantified as SUVs in leg bones. Taken together, these data support the use of ⁶⁴Cu-RGD as the osteoclast turnover imaging biomarker.