Abstract
Objective To investigate the value of integrin αvβ3 targeted micro positron emission tomography(microPET)/CT imaging with 68 Ca- 1,4,7,10- tetraazacyclododecane- N, N', N″, N‴- tetraacetic acid- arginine- glycine- aspartate peptide dimer(68 Ga- DOTA- RGD2)as radiotracer for the detection of breast cancer osteolytic bone metastases. Methods 68 Ga- DOTA- RGD2 was prepared via one- step method at 100℃for 15 min.Animal model with parathyroid hormone(PTH)- induced osteolysis in the calvarium was established and served as PTH group(BP). Biodistribution study of 68 Ga- DOTA- RGD2 was carried out in BP.Integrin receptor block study was done with pre- injection of high dose of DOTARGD2. 68 Ga- DOTA- RGD2 and 18 F- NaF microPET/CT imaging were perfromed respectively. Breast cancer osteolyic bone metastases was established via intrcardial injection of breast cancer cells. 68 Ga- DOTA- RGD2 microPET/CT imaging were perfromed for the detection of breast cancer osetolytic bone metastases. Animals were sarcrificed and bone lesions were harvested for pathological examination. Results 68 Ga- DOTA- RGD2 was stable in vitro and its radiopurity was as high as(96.4±2.1)% 3 h after its preparation.Its blood elimination was fast while its uptake by the liver and kidneys were relatively low.It was discharged soon after its intravenous injection.In the BP group, regional uptake of 68 Ga- DOTA- RGD2 in osteolytic lesion of calvarium(% ID/g)reached peak(5.14±0.65)60 min after tail vein injection.It was significantly more than that in BC group(2.06±0.35,t= 7.81,P<0.05).Bone radiotracer uptake ratio of osteolytic lesion to normal calvrium(O/N)was compared based microPET/CT imaging.Bone O/N of 68 Ga-DOTA- RGD2 was(6.10±0.97),significantly greater than that of 18 F- NaF(1.20±0.33,t= 10.17,P< 0.05). 68 Ga- DOTA- RGD2 microPET/CT imaging was able to demonstrate the ostelytic bone metastasis in calvarium, thoracic vertebrae and lung metastasis.They were confirmed by pathology results. Conclusion 68 Ga- DOTA- RGD2, as new integrinαvβ3 receptor targeting radiotracer, was potential for positive imaging and early detection of oseolytic lesion or breast cancer osteolytic bone metastasis. Key words: Osteolytic lesion; Bone metastasis; Integrin; Arg-gly-asp peptide; Molecular imaging
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