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

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• 作者：Ricarda Locher (1)
  Paola A. Erba (2)
  Burkhard Hirsch (3)
  Emilio Bombardieri (4)
  Leonardo Giovannoni (5)
  Dario Neri (6)
  Horst Dürkop (7)
  Hans D. Menssen (5)
  
• 关键词：Prostate cancer ; Prostatic hyperplasia ; ED ; B fibronectin ; Vascular targeting ; Pharmacodelivery ; 131I ; L19SIP dosimetry
• 刊名：Journal of Cancer Research and Clinical Oncology
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：140
• 期：1
• 页码：35-43
• 全文大小：702 KB
• 作者单位：Ricarda Locher (1)
  Paola A. Erba (2)
  Burkhard Hirsch (3)
  Emilio Bombardieri (4)
  Leonardo Giovannoni (5)
  Dario Neri (6)
  Horst Dürkop (7)
  Hans D. Menssen (5)
  
  1. Charité-Universit?tsmedizin Berlin, Berlin, Germany
  2. Regional Center of Nuclear Medicine, University of Pisa Medical School, Pisa, Italy
  3. Institute of Pathology, Charité-University Medicine Berlin, Berlin, Germany
  4. Montabone Unit for New Drug Development and Nuclear Medicine Division, National Institute of Cancer, Milan, Italy
  5. Philogen SpA, Siena, Italy
  6. Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
  7. Pathodiagnostik Berlin, Berlin, Germany
  
• ISSN：1432-1335

文摘

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.