title: Abundant in vitro expression of the oncofetal ED-B-containing fibronectin translates into selective pharmacodelivery of (131)I-L19SIP in a prostate cancer patient.
abstract: OBJECTIVE
  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 (131)I-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)/mm(2) in G3, G2, and G1 prostate cancers, respectively, and 7 (±5)/mm(2) 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 (131)I-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 (131)I-L19SIP in the prostate cancer tissues, qualifying ED-B as a promising target for selective pharmacodelivery of anticancer agents in prostate cancer.
authors.affiliation: Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Locher
authors.forename: Paola A
authors.initials: PA
authors.lastname: Erba
authors.forename: Burkhard
authors.initials: B
authors.lastname: Hirsch
authors.forename: Emilio
authors.initials: E
authors.lastname: Bombardieri
authors.forename: Leonardo
authors.initials: L
authors.lastname: Giovannoni
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.forename: Horst
authors.initials: H
authors.lastname: Dürkop
authors.forename: Hans D
authors.initials: HD
authors.lastname: Menssen
mesh_terms: D000906:Antibodies / Q000276:immunology; D001808:Blood Vessels / Q000378:metabolism; D000939:Epitopes / Q000032:analysis; D005353:Fibronectins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000378:metabolism; D016612:Paraffin Embedding; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D016719:Radioimmunodetection; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000493:pharmacokinetics*
chemical_list: D000906:Antibodies; D000939:Epitopes; C067625:FN1 protein, human; D005353:Fibronectins; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; C513931:SIP(L19) fusion protein