RT Journal Article
SR Electronic
T1 64Cu-RGD and microPET/CT as an imaging biomarker for osteoclast number in mouse models of negative and positive osteoclast regulation
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1958
OP 1958
VO 50
IS supplement 2
A1 Alex Zheleznyak
A1 Thaddeus Wadas
A1 Christopher  Sherman
A1 Paul Kostenuik
A1 Carolyn  Anderson
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1958.abstract
AB 1958 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.