Clinical study of 99mTc-3P-RGD2 peptide imaging in osteolytic bone metastasis

Guoqiang Shao; Wei Gu; Muhong Guo; Shiming Zang; Jinjing Fu; Shuang Liu; Feng Wang; Zizheng Wang

doi:10.18632/oncotarget.17486

Clinical study of ^99mTc-3P-RGD2 peptide imaging in osteolytic bone metastasis

Oncotarget. 2017 Apr 27;8(43):75587-75596. doi: 10.18632/oncotarget.17486. eCollection 2017 Sep 26.

Authors

Guoqiang Shao¹, Wei Gu², Muhong Guo¹, Shiming Zang¹, Jinjing Fu¹, Shuang Liu³, Feng Wang¹, Zizheng Wang¹

Affiliations

¹ Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
² Department of Respiration, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
³ School of Health Sciences, Purdue University, West Lafayette, IN, USA.

Abstract

Objective: To investigate the value of integrin α_vβ₃ targeted imaging with ^99mTc-HYNIC-PEG₄-E[PEG₄-c(RGDfk)]₂ (^99mTc-3P-RGD₂) as a radiotracer in dectecting osteolytic bone metastases.

Methods: This is a retrospective study involving a cohort of 69 consecutive patients including 59 with lung cancer and 10 with other cancers. Patients were required to receive whole body scan (WBS) and regional SPECT/CT imaging with ^99mTc-3P-RGD₂ (RGD imaging) and ^99mTc-MDP (MDP imaging) as a radiotracer successively within days. Final diagnosis was based on comprehensive assessment of all available data including case history, CT, MRI, SPECT/CT, PET/CT, histopathology and 6-12 months follow-up. Visual observation and semiquantitative analysis (T/N: tracer uptake ratio of osteolytic metastases to normal bone) of ^99mTc-3P-RGD₂ or ^99mTc-MDP imaging were performed and their detective values for osteolytic metastases were compared.

Results: A total of 131 osteolytic metastatic lesions were retrospectively studied. Osteolytic metastases mainly presented as "hot region", occasionally as "cool or normal region" on RGD imaging. The detection sensitivity of RGD WBS for osteolytic metastases was significantly higher than that of ^99mTc-MDP WBS (80.9% vs. 46.6%, p<0.01). The sensitivity increased to 96.2% (126/131) when combining with SPECT/CT. ^99mTc-3P-RGD₂ imaging also promoted the detection of unknown primary tumor, lymph node metastases and offered information for clinical staging. T/N of ^99mTc-3P-RGD₂ in lung adenocarcinoma osteolytic metastases showed no statistical difference compared with that in squamous-cell carcinoma (6.84±3.46 vs. 7.33±3.22, t = 0.39, p = 0.71). Whereas, it was higher in osteolytic metastases from lung cancer than that from thyroid cancer (7.05±3.01 vs. 4.11±2.67, p = 0.03).

Conclusion: ^99mTc-3P-RGD₂ peptide imaging showed great potential for detection of osteolytic bone metastasis due to high expression level of integrin αvβ3 on osteoclast and most tumor cells.

Keywords: RGD peptide; integrin αvβ3; lung cancer; osteolytic metastasis; targeted imaging.