J Cancer 2013; 4(2):133-145. doi:10.7150/jca.5635


Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications

Junjie Li1,2, Raymond Oyen1, Alfons Verbruggen3, Yicheng Ni1,2,✉

1. Department of Imaging and Pathology, Biomedical Sciences Group; KU Leuven, Belgium.
2. Molecular Small Animal Imaging Center, Faculty of Medicine; KU Leuven, Belgium.
3. Laboratory of Radiopharmacy, Faculty of Pharmaceutical Sciences, KU Leuven, Belgium.


Hitting the evasive tumor cells proves challenging in targeted cancer therapies. A general and unconventional anticancer approach namely small molecule sequential dual-targeting theragnostic strategy (SMSDTTS) has recently been introduced with the aims to target and debulk the tumor mass, wipe out the residual tumor cells, and meanwhile enable cancer detectability. This dual targeting approach works in two steps for systemic delivery of two naturally derived drugs. First, an anti-tubulin vascular disrupting agent, e.g., combretastatin A4 phosphate (CA4P), is injected to selectively cut off tumor blood supply and to cause massive necrosis, which nevertheless always leaves peripheral tumor residues. Secondly, a necrosis-avid radiopharmaceutical, namely 131I-hypericin (131I-Hyp), is administered the next day, which accumulates in intratumoral necrosis and irradiates the residual cancer cells with beta particles. Theoretically, this complementary targeted approach may biologically and radioactively ablate solid tumors and reduce the risk of local recurrence, remote metastases, and thus cancer mortality. Meanwhile, the emitted gamma rays facilitate radio-scintigraphy to detect tumors and follow up the therapy, hence a simultaneous theragnostic approach. SMSDTTS has now shown promise from multicenter animal experiments and may demonstrate unique anticancer efficacy in upcoming preliminary clinical trials. In this short review article, information about the two involved agents, the rationale of SMSDTTS, its preclinical antitumor efficacy, multifocal targetability, simultaneous theragnostic property, and toxicities of the dose regimens are summarized. Meanwhile, possible drawbacks, practical challenges and future improvement with SMSDTTS are discussed, which hopefully may help to push forward this strategy from preclinical experiments towards possible clinical applications.

Keywords: small molecule sequential dual-targeting theragnostic strategy, SMSDTTS, vascular disrupting agent, combretastatin A4 phosphate, necrosis avid contrast agent, hypericin.

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How to cite this article:
Li J, Oyen R, Verbruggen A, Ni Y. Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications. J Cancer 2013; 4(2):133-145. doi:10.7150/jca.5635. Available from http://www.jcancer.org/v04p0133.htm