PT  - JOURNAL ARTICLE
AU  - Ying Miao
AU  - Biao Li
TI  - Therapeutic delivery of miR-143 targeting tumor metabolism in poorly differentiated thyroid cancer xenografts and efficacy evaluation using <sup>18</sup>F-FDG microPET-CT
DP  - 2018 May 01
TA  - Journal of Nuclear Medicine
PG  - 1250--1250
VI  - 59
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/59/supplement_1/1250.short
4100  - http://jnm.snmjournals.org/content/59/supplement_1/1250.full
SO  - J Nucl Med2018 May 01; 59
AB  - 1250Objectives: Aggressive thyroid carcinoma exhibits higher glucose metabolic activity, and tumor metabolism is emerging as anticancer target for therapeutic strategy. We previously identified hexokinase 2(HK2), the first rate-limiting glycolytic enzyme, as a direct target of miR-143. Here, we explored the therapeutic potential of chemically modified miR-143 formulation in an animal model of human poorly differentiated thyroid cancer (PDTC), and whether 18F-FDG microPET/CT could be exploited to assess the therapeutic efficacy of miR-143. METHODS: Mice bearing FTC-133 subcutaneous tumors were treated with chemically modified miR-143 (miR-143 agomir) or scrambled negative control RNA (Ctrl RNA agomir), formulated with a neutral lipid-based delivery reagent and administered to PDTC xenografts by tail vein injection every three days for six cycles. Tumor volumes and mice weights were monitored every three days throughout the study. The animals were subjected to 18F-FDG microPET/CT on day 0 and day 18 respectively. Blood samples were collected from animal model for routine blood tests and biochemical tests to assess the therapeutic toxicity. RESULTS: The administration of miR-143 agomir markedly slowed the rates of tumor growth in PDTC xenografts. SUVmax and SUVmean of 18F-FDG in miR-143 treated groups showed a dramatically lower level compared with the control groups. No significant loss of body weight was observed in miR-143-treated group, and no significant difference was detected in clinical chemical tests among the groups. Conclusions: Our results suggest that miR-143 is a potential therapeutic target for PDTC. 18F-FDG microPET/CT could be used to specifically evaluate the therapeutic response of PDTC xenografts to miR-143. Furthermore, the animals tolerate the treatment well.