Skip to main content

Advertisement

SpringerLink
Log in

Influence of the vascular damaging agents DMXAA and ZD6126 on hypericin distribution and accumulation in RIF-1 tumors

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

We investigated the influence of two types of vascular damaging agents (VDAs) (DMXAA vs. ZD6126) and sequence of administration (VDA 24 h before HYP vs. HYP 1 h before VDA) to evaluate the effect on hypericin (HYP) accumulation and distribution in necrotic tumors.

Methods

Frozen sections of dorsally inoculated RIF-1 tumors were analyzed by fluorescence microscopy and H&E stained for histological evaluation. The localization of HYP was assessed both qualitatively and semi-quantitatively in necrotic tumor, viable tumor, or nontarget host tissue.

Results

Whereas the type of VDA did not influence HYP accumulation and distribution, a clear advantage could be seen when administering VDA 24 h before HYP compared to HYP 1 h before VDA, pointing toward the absence of a “trapping” mechanism. In DMXAA-treated and not in ZD6126-treated tumors, spotty fluorescence was observed which is likely to be a consequence of neutrophil phagocytosis. Dexamethasone treatment neither did influence this phenomenon nor did change HYP uptake in necrotic tumor.

Conclusions

We conclude that HYP accumulation is optimal when it is administered after VDA injection. We also found that HYP accumulation in necrosis is not changed when using VDAs with different working mechanisms. This insight provides a rationale for tumor necrosis therapy (TNT) using iodine-131-labeled hypericin ([131I]-HYP) in combination with VDAs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Chen FM, Taylor CR, Epstein AL (1989) Tumor necrosis treatment of ME-180 human cervical carcinoma model with 131I-labeled TNT-1 monoclonal antibody. Cancer Res 49(16):4578–4585

    PubMed  CAS  Google Scholar 

  • Chen B, Xu Y, Roskams T, Delaey E, Agostinis P, Vandenheede JR, de Witte P (2001) Efficacy of antitumoral photodynamic therapy with hypericin: relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model. Int J Cancer 93(2):275–282. doi:10.1002/ijc.1324

    Article  PubMed  CAS  Google Scholar 

  • Ching LM, Zwain S, Baguley BC (2004) Relationship between tumour endothelial cell apoptosis and tumour blood flow shutdown following treatment with the antivascular agent DMXAA in mice. Br J Cancer 90(4):906–910. doi:10.1038/sj.bjc.6601606

    Article  PubMed  CAS  Google Scholar 

  • Cooper EH, Bedford AJ, Kenny TE (1975) Cell death in normal and malignant tissues. Adv Cancer Res 21:59–120

    Article  PubMed  CAS  Google Scholar 

  • Epstein AL, Chen FM, Taylor CR (1988) A novel method for the detection of necrotic lesions in human cancers. Cancer Res 48(20):5842–5848

    PubMed  CAS  Google Scholar 

  • Falk H, Meyer J, Oberreiter M (1993) A convenient semisynthetic route to hypericin. Monatshefte Fur Chemie 124(3):339–341

    Article  CAS  Google Scholar 

  • Finotto S, Mekori YA, Metcalfe DD (1997) Glucocorticoids decrease tissue mast cell number by reducing the production of the c-kit ligand, stem cell factor, by resident cells: in vitro and in vivo evidence in murine systems. J Clin Invest 99(7):1721–1728. doi:10.1172/JCI119336

    Article  PubMed  CAS  Google Scholar 

  • Fonge H, Vunckx K, Wang H, Feng Y, Mortelmans L, Nuyts J, Bormans G, Verbruggen A, Ni Y (2008) Non-invasive detection and quantification of acute myocardial infarction in rabbits using mono-[123I] iodohypericin microSPECT. Eur Heart J 29(2):260–269. doi:10.1093/eurheartj/ehm588

    Article  PubMed  CAS  Google Scholar 

  • Hdeib A, Sloan AE (2011) Convection-enhanced delivery of [131I]-chTNT-1/B mAB for treatment of high-grade adult gliomas. Expert Opin Biol Ther 11(6):799–806. doi:10.1517/14712598.2011.579097

    Article  PubMed  CAS  Google Scholar 

  • Horsman MR, Murata R (2003) Vascular targeting effects of ZD6126 in a C3H mouse mammary carcinoma and the enhancement of radiation response. Int J Radiat Oncol Biol Phys 57(4):1047–1055. doi:10.1016/S0360-3016(03)00769-7

    Article  PubMed  CAS  Google Scholar 

  • Horsman MR, Siemann DW (2006) Pathophysiologic effects of vascular-targeting agents and the implications for combination with conventional therapies. Cancer Res 66(24):11520–11539. doi:10.1158/0008-5472.CAN-06-2848

    Article  PubMed  CAS  Google Scholar 

  • Jain M, Venkatraman G, Batra SK (2007) Optimization of radio immunotherapy of solid tumors: biological impediments and their modulation. Clin Cancer Res 13(5):1374–1382. doi:1078-0432.CCR-06-2436

    Article  PubMed  CAS  Google Scholar 

  • Kanthou C, Tozer GM (2009) Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies. Int J Exp Pathol 90(3):284–294. doi:10.1111/j.1365-2613.2009.00651.x

    Article  PubMed  CAS  Google Scholar 

  • Koljenovic S, Choo-Smith LP, Bakker Schut TC, Kros JM, van den Berge HJ, Puppels GJ (2002) Discriminating vital tumor from necrotic tissue in human glioblastoma tissue samples by Raman spectroscopy. Lab Invest 82(10):1265–1277

    PubMed  CAS  Google Scholar 

  • Li J, Sun Z, Zhang J, Shao H, Miranda Cona M, Wang H, Marysael T, Chen F, Prinsen K, Zhou L, Huang D, Nuyts J, Yu J, Meng B, Bormans G, Fang Z, de Witte P, Li Y, Verbruggen A, Wang X, Mortelmans L, Xu K, Marchal G, Ni Y (2011) A dual-targeting anticancer approach: soil and seed principle. Radiology 260:799–807. doi:radiol.11102120

    Article  PubMed  Google Scholar 

  • McKeage MJ, Baguley BC (2010) Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer. Cancer 116(8):1859–1871. doi:10.1002/cncr.24975

    Article  PubMed  CAS  Google Scholar 

  • Miller TA, Schaefer FW III (2007) Changes in mouse circulating leukocyte numbers in C57BL/6 mice immunosuppressed with dexamethasone for Cryptosporidium parvum oocyst production. Vet Parasitol 149(3–4):147–157. doi:10.1016/j.vetpar.2007.08.017

    Article  PubMed  CAS  Google Scholar 

  • Miyachi Y (2000) Pharmacologic modulation of neutrophil functions. Clin Dermatol 18(3):369–373

    Article  PubMed  CAS  Google Scholar 

  • Ni Y, Bormans G, Chen F, Verbruggen A, Marchal G (2005) Necrosis avid contrast agents: functional similarity versus structural diversity. Invest Radiol 40(8):526–535

    Article  PubMed  CAS  Google Scholar 

  • Ni Y, Huyghe D, Verbeke K, de Witte PA, Nuyts J, Mortelmans L, Chen F, Marchal G, Verbruggen AM, Bormans GM (2006) First preclinical evaluation of mono-[123I] iodohypericin as a necrosis-avid tracer agent. Eur J Nucl Med Mol Imaging 33(5):595–601. doi:10.1007/s00259-005-0013-2

    Article  PubMed  CAS  Google Scholar 

  • Song S, Xiong C, Zhou M, Lu W, Huang Q, Ku G, Zhao J, Flores LG Jr, Ni Y, Li C (2011) Small-animal PET of tumor damage induced by photothermal ablation with 64Cu-bis-DOTA-hypericin. J Nucl Med 52(5):792–799. doi:jnumed.110.086116

    Article  PubMed  CAS  Google Scholar 

  • Tozer GM, Kanthou C, Baguley BC (2005) Disrupting tumour blood vessels. Nat Rev Cancer 5(6):423–435. doi:10.1038/nrc1628

    Article  PubMed  CAS  Google Scholar 

  • Van de Putte M, Roskams T, Vandenheede JR, Agostinis P, de Witte PA (2005) Elucidation of the tumoritropic principle of hypericin. Br J Cancer 92(8):1406–1413. doi:10.1038/sj.bjc.6602512

    Article  PubMed  Google Scholar 

  • Van de Putte M, Ni Y, De Witte PA (2008a) Exploration of the mechanism underlying the tumor necrosis avidity of hypericin. Oncol Rep 19(4):921–926

    PubMed  Google Scholar 

  • Van de Putte M, Wang H, Chen F, de Witte PA, Ni Y (2008b) Hypericin as a marker for determination of tissue viability after intratumoral ethanol injection in a murine liver tumor model. Acad Radiol 15(1):107–113. doi:10.1016/j.acra.2007.08.008

    Article  PubMed  Google Scholar 

  • Van de Putte M, Wang H, Chen F, De Witte PA, Ni Y (2008c) Hypericin as a marker for determination of tissue viability after radiofrequency ablation in a murine liver tumor model. Oncol Rep 19(4):927–932

    PubMed  Google Scholar 

  • Wang H, Cao C, Li B, Chen S, Yin J, Shi J, Ye D, Tao Q, Hu P, Epstein A, Ju D (2008) Immunogenicity of iodine 131 chimeric tumor necrosis therapy monoclonal antibody in advanced lung cancer patients. Cancer Immunol Immunother 57(5):677–684. doi:10.1007/s00262-007-0406-0

    Article  PubMed  CAS  Google Scholar 

  • Wang LC, Thomsen L, Sutherland R, Reddy CB, Tijono SM, Chen CJ, Angel CE, Dunbar PR, Ching LM (2009) Neutrophil influx and chemokine production during the early phases of the antitumor response to the vascular disrupting agent DMXAA (ASA404). Neoplasia 11(8):793–803

    PubMed  CAS  Google Scholar 

  • Wang H, Li J, Chen F, De Keyzer F, Yu J, Feng Y, Nuyts J, Marchal G, Ni Y (2010) Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours. Eur Radiol 20(8):2013–2026. doi:10.1007/s00330-010-1743-5

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This research was funded by a PhD grant from the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen).

Conflict of interest

The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

Author information

Authors and Affiliations

  1. Laboratorium voor Farmaceutische Biologie, Faculteit Farmaceutische Wetenschappen, K. U. Leuven, Herestraat 49-Bus 824, 3000, Leuven, Belgium

    Thierry Marysael & Peter de Witte

  2. Departement Radiology, Faculteit Geneeskunde, K. U. Leuven, Leuven, Belgium

    Yicheng Ni

  3. Departement Medisch Diagnostische Wetenschappen, Faculteit Geneeskunde, K. U. Leuven, Leuven, Belgium

    Evelyne Lerut

Authors
  1. Thierry Marysael
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yicheng Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evelyne Lerut
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter de Witte
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter de Witte.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marysael, T., Ni, Y., Lerut, E. et al. Influence of the vascular damaging agents DMXAA and ZD6126 on hypericin distribution and accumulation in RIF-1 tumors. J Cancer Res Clin Oncol 137, 1619–1627 (2011). https://doi.org/10.1007/s00432-011-1032-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-011-1032-y

Keywords

Search

Navigation