Abstract 1767: Oncocidia: a small molecule dual targeting pan-anticancer theragnostic strategy
2014; American Association for Cancer Research; Volume: 74; Issue: 19_Supplement Linguagem: Inglês
10.1158/1538-7445.am2014-1767
ISSN1538-7445
Autores Tópico(s)Photodynamic Therapy Research Studies
ResumoAbstract Research on imaging contrast media over the last decades has led to the discovery of small molecular necrosis-avid compounds (NACs) for potential applications in diagnosis of myocardial infarction and therapeutic assessment of tumor ablation using MRI, nuclear scintigraphy and optical imaging [1,2]. The in vivo affinity of NACs to necrosis appears to be orders of magnitude higher than in vivo antigen-antibody, ligand-receptor and biotin-avidin interactions, implying their possible superb applications. Based on a soil-to-seeds hypothesis [3], this stroma targetability has now been extended from diagnostic to theragnostic utilities by combined use of vascular disrupting agents (VDAs) to formulate a novel anticancer approach, namely a small molecule sequential dual targeting pan-anticancer theragnostic strategy or briefly OncoCiDia. The dual targeting property and conjugated iodine-131 that emits both beta and gamma radiations render solid cancers (Onco) with both tumoricidal (Ci) and diagnostic (Dia) effects, thus the acronym of OncoCiDia. Instead of directly attacking multimutant and refractory cancer cells (seeds) as elaborated in most other cancer therapies, OncoCiDia treats solid malignancies overnight by selectively destroying and radioactively sterilizing their microenvironment (soil) in two steps [3]. On day one, a VDA such as Combretastatin A4 phosphate (CA4P) is intravenously (iv) injected to specifically shut down tumoral blood vessels by disrupting the immature endothelium and to cause ischemic tumor necrosis. However, peripheral residual cancer cells always survive as the seeds for tumor re-growth, leading to cancer relapse. Thus, on day two, a NAC such as hypericin (Hyp) carrying the beta emitter iodine-131 is iv infused, which selectively accumulates at the newly generated intratumoral necrosis to create a harsh environment with crossfire radiation and lethally irradiates the adjacent viable tumor cells to prevent their repopulation. One episode of OncoCiDia exerts persistent theragnostic effects over weeks to months due to the long decay half-life of 8 days with iodine-131 and prolonged necrosis target residence of 131I-Hyp. Multicenter proof-of-principle studies and extensive preclinical investigations on the efficacy, safety, formulations and dosimetry have been conducted and the results will be demonstrated in details. Our studies suggest that OncoCiDia appears to be a novel unconventional anticancer strategy that may offer a simple, workable, affordable and generic solution for diverse cancers, and deserve further exploitation [3]. References: 1. Ni Y, et al. Necrosis avid contrast agents: functional similarity versus structural diversity. Invest Radiol 2005; 40: 526-35. 2. Ni Y. Metalloporphyrins and functional analogues as MRI contrast agents. Current Medical Imaging Reviews 2008; 4: 96-112. 3. Li J, et al. A dual targeting anticancer approach: soil and seed principle. Radiology 2011; 260:799-807. Citation Format: Yicheng Ni. Oncocidia: a small molecule dual targeting pan-anticancer theragnostic strategy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1767. doi:10.1158/1538-7445.AM2014-1767
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