PT  - JOURNAL ARTICLE
AU  - Chenran Zhang
AU  - Liquan Gao
AU  - Hao Liu
AU  - Bing Jia
AU  - Fan Wang
AU  - Zhaofei Liu
TI  - Tumor-associated macrophage (TAM)-targeted photoimmunotherapy for the inhibition of tumor growth and metastasis in a tumor model of sorafenib resistance
DP  - 2016 May 01
TA  - Journal of Nuclear Medicine
PG  - 84--84
VI  - 57
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/57/supplement_2/84.short
4100  - http://jnm.snmjournals.org/content/57/supplement_2/84.full
SO  - J Nucl Med2016 May 01; 57
AB  - 84Objectives TAMs play essential roles in tumor invasion and metastasis, and contribute to drug resistance. Clinical evidence suggests that TAM levels are correlated with local tumor relapse, distant metastasis, and poor prognosis in patients. We investigated the potential application of a TAM-targeted probe (IRD-αCD206) to near-infrared fluorescence (NIRF) imaging and photoimmunotherapy (PIT) of tumors resistant to treatment with the kinase inhibitor sorafenib.Methods IRD-αCD206 was synthesized by conjugating a monoclonal anti-CD206 antibody with IRDye700. The effectiveness of IRD-αCD206 was evaluated in vitro and in vivo.Results Sorafenib treatment had no effect on tumor growth in a 4T1 mouse model of breast cancer, but induced M2 macrophage polarization in tumors. M2 macrophage recruitment by sorafenib-treated 4T1 tumors was noninvasively visualized by in vivo NIRF imaging of IRD-αCD206. SPECT/CT and intratumoral microdistribution analysis indicated TAM-specific localization of the IRD-αCD206 probe in 4T1 tumors after several rounds of sorafenib treatment. Upon light irradiation, IRD-αCD206 suppressed the growth of sorafenib-resistant tumors. In vivo CT imaging and ex vivo histological analysis confirmed the inhibition of lung metastasis in mice by IRD-αCD206 PIT.Conclusions The recruitment of TAMs by tumors was noninvasively visualized by NIRF imaging of IRD-αCD206. Upon irradiation, IRD-αCD206 PIT inhibited the growth of subcutaneous 4T1 tumors and prevented their metastasis to the lungs. These results suggest that TAM-targeted PIT is a promising strategy for treating tumors that are resistant to conventional drugs.