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Abundant in vitro expression of the oncofetal ED-B-containing fibronectin translates into selective pharmacodelivery of 131I-L19SIP in a prostate cancer patient

Abstract

Purpose

The extradomain B of fibronectin (ED-B) is a promising vascular target for selective pharmacodelivery in cancer patients. We analyzed a large series of prostatectomies from patients with prostate cancer, hyperplastic prostate disease, and normal prostates to study extent and tumor-selectivity of ED-B expression.

Methods

Using immunohistology, 68 adenocarcinomas of the prostate or prostate cancer-inflicted lymph nodes, 4 samples of benign prostatic hyperplasia, and 6 normal prostate glands were studied for ED-B expressing newly formed blood vessels. Further, we treated an advanced prostate cancer patient with the anti-ED-B antibody 131I-L19SIP to study in vivo target accessibility.

Results

ED-B-positive blood vessels were found significantly more frequent in prostate cancers as compared with peritumoral prostate tissues or normal prostate glands, independent of tumor differentiation. The ED-B-positive blood vessels’ density was 97 (±23), 65 (±9), and 59 (±9)/mm2 in G3, G2, and G1 prostate cancers, respectively, and 7 (±5)/mm2 in normal prostate glands. In high-grade (G3) prostate cancers, also the peritumoral tissue showed a higher density of ED-B vessels than normal prostate glands. Similar results were obtained when ED-B-positive vessel density was expressed as a fraction of CD34-positive vessel density. Finally, selective uptake of ED-B-binding 131I-L19SIP to tumor lesions was found in an advanced prostate cancer patient by whole-body planar scintigraphy.

Conclusions

ED-B-positive blood vessels were found to a large extent in prostate cancer tissues, but only rarely in normal prostates or benign prostatic hyperplasia. Whole-body planar scintigraphy in a prostate cancer patient confirmed selective uptake of 131I-L19SIP in the prostate cancer tissues, qualifying ED-B as a promising target for selective pharmacodelivery of anticancer agents in prostate cancer.

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Acknowledgments

The authors thank Conny Cieluch and Sandra Maier for their excellent technical assistance in processing the tissue samples and sections.

Conflict of interest

R.L., P.A.E., B.H., E.B., and H.D. declare no conflicting financial interests. L.G. and H.D.M. are employees of Philogen, SpA, Siena, Italy, sponsor of the clinical trials with radretumab (131I-L19SIP). D.N. is a co-founder and owns stocks of Philogen.

Author information

Correspondence to Hans D. Menssen.

Additional information

Hans D. Menssen and Horst Dürkop have contributed equally to this work.

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Locher, R., Erba, P.A., Hirsch, B. et al. Abundant in vitro expression of the oncofetal ED-B-containing fibronectin translates into selective pharmacodelivery of 131I-L19SIP in a prostate cancer patient. J Cancer Res Clin Oncol 140, 35–43 (2014). https://doi.org/10.1007/s00432-013-1538-6

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Keywords

  • Prostate cancer
  • Prostatic hyperplasia
  • ED-B fibronectin
  • Vascular targeting
  • Pharmacodelivery
  • 131I-L19SIP dosimetry