Medical Imaging (Track)




Medical Imaging Research Leads to Discovery of a New Anticancer Strategy

Yicheng Ni
Department of Radiology, University Hospitals, K.U. Leuven, Herestraat 49, B-3000, Leuven, Belgium

Abstract:

Background: Our research on experimental radiology over the last 2 decades has led to the discovery of small molecular necrosis-avid compounds (NACs) for imaging diagnosis of myocardial infarction and therapeutic assessment of RF tumor ablation with MRI, nuclear scintigraphy and optical imaging. This stroma targetability has now been extended from diagnostic to therapeutic utilities by combination with the use of vascular disrupting agents (VDAs) to formulate a novel anticancer approach namely small-molecular sequential dual targeting theragnostic strategy (SMSDTTS), in which instead of directly attacking multimutant cancer cells (seeds), we sought to treat or cure solid malignant tumors by selectively destroying their microenvironment (soil).

Materials and Methods: Combretastatin A4 phosphate (CA4P) and Hypericin, representative of VDAs and NACs respectively, are both small molecular, naturally and synthetically derivable, intravenously injectable, and of unique targetabilities. We first injected CA4P at 10 mg/kg to cause tumor necrosis and to create the next target. We radiolabeled Hypericin with iodine-131 to formulate mono-[¹³¹I]iodohypericin or [¹³¹I]MIH, which was then injected at 300 MBq/kg 24h post CA4P. [¹³¹I]MIH accumulated in necrotic tumor, killing residual cancer cells by cross-fire irradiation and preventing tumor re-growth. We studied SMSDTTS with 24 rats of 48 implanted intrahepatic liver rhabdomyosarcomas (R1) in vehicle-control, single-targeting (CA4P or [¹³¹I]MIH) and dual-targeting (CA4P plus [131I]MIH) groups using in vivo MRI and scintiscans, and ex vivo gamma-counting, autoradiography and histology. Further validations are ongoing using other tumor models of different animal species.

Results: R1 tumor size in vehicle-controls doubled that in single-targeting groups (p < 0.01), and was 5-times that in dual-targeting group (p < 0.001). Necrotic tumors appeared as hot-spots on scintiscans, corresponding to 3.34 % ID/g of [¹³¹I]MIH and a target-to-liver ratio 20. We obtained similar results in other allograft models in rats, mice and rabbits (n=74) with complete tumor remission in 41% W256 tumors and significantly reduced lung metastasis in VX2 carcinoma after one SMSDTTS episode.

Conclusion: Our multicenter animal experiments with proof-of-principle evidence suggest that the new combined drug therapy SMSDTTS may present a more simple, workable and affordable solution for diverse cancers, and deserve further exploitation.  

Keywords: medical imaging, cancer, necrosis, targeting therapy, diagnosis.