Paolo Marra, Presenter: Nothing to Disclose

Antonio Esposito MD, Abstract Co-Author: Nothing to Disclose

Tamara Canu RT, Abstract Co-Author: Nothing to Disclose

Giovanni Sitia, Abstract Co-Author: Nothing to Disclose

Francesco Aldo De Cobelli MD, Abstract Co-Author: Nothing to Disclose

Alessandro Del Maschio MD, Abstract Co-Author: Nothing to Disclose

In primary and metastatic liver tumors characterized by neovascularization the accumulation of Tie2-expressing monocytes (TEMs) is common. They are tumor-associated macrophages derived from the hematopoietic system, with pro-angiogenic activity. Our purpose was to genetically modify these cells to express and selectively deliver interferon-α to liver metastases. Antitumor efficacy was assessed by volumetric analyses at MRI in a mouse model of liver CRC metastases.

Liver metastases were induced injecting 5x103 CT26-GFP cells through the splenic vein in 30 CB6F1 mice: 14/26 were previously transplanted with TEMs engineered to express IFNα under the Tie2 promoter (IFN-group); 12/26 were transplanted with TEMs engineered to express green-fluorescent-protein under the Tie2 promoter (Placebo-group); 4/26 control mice were un-manipulated before metastases induction (Control-group). In other 6 of 11 mice injected with metastatic cells, IFNα was administered systemically at a dose of 25µg day. Starting from day 14 after metastases induction serial in vivo liver EOB-DTPA-enhanced MRI analyses with a 7-Tesla scanner were carried out for the detection and the volumetric assessment of metastases.  

The incidence of liver metastases was lower in IFN-group than in Placebo and Control groups both at 14 (0%vs57%vs50%; p<0,05) and at 34 days (11%vs100%vs100%; p=0,002) from CT26-GFP cells injection. 3 IFN-mice that developed metastases at day 21 presented disease remission with no metastases at day 54. Average tumor volume was significantly lower in IFN-group than in Placebo and Control groups with a mean value between time points respectively of 1,53vs128,86vs38,92 mm3 (p<0,01). At day 54 Placebo and Control mice were dead vs only 11% of IFN-mice (p=0,001). Also the systemic administration of IFNα reduced liver metastases incidence in treated mice (IFN vs Placebo: 0% vs 60% at 14 and 21 days; p<0,05).

Selective hepatic or systemic deliver of IFNα seems to prevent CRC metastases in a mouse model of disease: incidence and volume reduction at MRI should be considered a reliable and easy detectable marker of biological efficacy as it correlates with survival rates.

MR is a reliable and practical tool for the evaluation of efficacy of new therapies in mouse models of disease: with it, a potential reduction of the time required for the preclinical experimental phase may be achieved.

Marra, P, Esposito, A, Canu, T, Sitia, G, De Cobelli, F, Del Maschio, A, Efficacy of Interferon-α in the Prevention of Colorectal Cancer Metastases: Assessment by 7 Tesla Liver Magnetic Resonance (MR) in a Mouse Model of Disease.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14045776.html