Eine Übersicht über die Molekulare Radiologie. Teil 1: Gentherapie*

Zusammenfassung.

Der Begriff Molekulare Radiologie beschreibt die Schnittmenge zwischen der radiologischen Bildgebung und der interventionellen Radiologie auf der einen Seite und der Molekularbiologie auf der anderen Seite. Im Bereich der Bildgebung entwickeln sich derzeit Methoden, mit denen eine Darstellung molekularer Vorgänge, d. h. Genexpression und Proteinfunktionen, in vivo darstellbar sind. Diese Methoden eröffnen neue Möglichkeiten für die Forschung und die klinische Diagnostik und werden im zweiten Teil dieses Review dargestellt. Der hier vorliegende Teil bietet eine Übersicht über die aktuellen Entwicklungen der Gentherapie aus radiologischer Sicht und beleuchtet die Rolle, die unser Fachgebiet in diesem Bereich zu spielen vermag.

A Review of Molecular Radiology. Part I: Gene Therapy.

The term molecular radiology intermediate region between radiological imaging and interventional radiology on the one side and molecular biology on the other. In the field of imaging methods are currently being developed by which molecular processes, i. e., gene expression and protein function, can be visualized in vivo. These techniques open new perspectives for research and clinical diagnosis and will be presented in the second part of this review. The present part provides a survey of current developments in gene therapy from a radiological point of view and highlights the part that our specialty may play in this field.

Interventionen - Gene - Genetik - Gentherapie - Atherosklerose - Restenose

Interventional - Genes and genetics - Gene therapy - Arteriosclerosis

Literatur

• 1 Blau H, Khavari P. Gene therapy: Progress, problems, prospects.  Nat Med. 1997;  3 612-613
• 2 Thomas J W, Kuo M D, Chawla M, Waugh J M, Yuksel E, Wright K C, et al. Vascular Gene Therapy.  RadioGraphics. 1998;  18 1373-1394
• 3 Wagner R W. Gene inhibition using antisense oligodeoxynucleotides.  Nature. 1994;  372 333-335
• 4 Hartmann G, Bidlingmaier M, Tschöp K, Eigler A, Hacker U, Endres S. Antisense-Oligonukleotide. Nukleinsäuren zur gezielten Synthesehemmung krankheitsfördernder Proteine.  Dt Ärztebl. 1998;  95 A1524-1530
• 5 Cech T R, Bass B L. Biological catalysis by RNA.  Annu Rev Biochem. 1986;  55 599-629
• 6 Ross G, Erickson R, Knorr D, et al. Gene therapy in the united states: a five-year status report.  Hum Gene Ther. 1996;  7 1781-1790
• 7 Ferrari F K, Xiao X, McCarthy D, Samulski R J. New developments in the generation of Ad-free, high titer rAAV gene therapy vectors.  Nat Med. 1997;  3 1295-1297
• 8 Clague M J. Molecular aspects of the endocytic pathway.  Biochem J. 1998;  336 271-282
• 9 Feldman L J, Tahlil O, Steg G. Perspectives of arterial gene therapy for the prevention of restenosis.  Cardiovasc Res. 1996;  32 194-207
• 10 van Kalle C, Veelken H, Rosenthal F M. Gentherapie in der Onkologie.  Onkologe. 1999;  5 898-909
• 11 Thompson G B. Apoptosis in the pathogenesis and treatment of disease.  Science. 1995;  267 1456-1462
• 12 Roth J A, Ngyen D, Lawrence D D, Klemp B L, Carrasco C H, Ferson D Z, et al. Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer.  Nat Med. 1996;  2 985-991
• 13 Singhal S, Kaiser L R. Cancer chemotherapy using suicide genes.  Surg Oncol Clin N Am. 1998;  7 505-536
• 14 Gibbons G H, Dzau V J. Molecular therapies for vascular disease.  Science. 1996;  272 689-693
• 15 Dranoff G, Jaffe E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long lasting anti-tumor immunity.  Proc Natl Acad Sci USA. 1993;  90 3539-3543
• 16 Nabel G J, Nabel E G, Yang Z H, et al. Direct gene transfer with DNA-liposome complexesin melanoma: expression; biologic activity, and lack of toxicity in humans.  Proc Natl Acad Sci USA. 1993;  90 11307-11311
• 17 Hwu P, Shafter G E, Treisma J, et al. Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor g chain.  J Exp Med. 1993;  178 361-366
• 18 Stinchcomb D T. Constraining the cell cycle: Regulationg cell division and differentiation by gene therapy.  Nat Med. 1995;  1 1004-1006
• 19 Monia B, Johnston J F, Geiger T, Muller M, Fabro D. Antitumor activity of a phosphorothiate antisense oligonucleotide targeted against c-raf kinase.  Nat Med. 1996;  2 668-675
• 20 Laitinen M, Ylä-Hertuala S. Adventitial gene transfer to arterial wall.  Pharmacological Research. 1998;  37 251-254
• 21 Nabel E G, Pompili V J, Plautz G E, Nabel G J. Gene transfer and vascular disease.  Cardiovasc Res. 1994;  28 445-455
• 22 Carmeliet P, Collen D. Gene manipulation and transfer of the plasminogen and coagulation system in mice.  Semin Thromb Hemost. 1996;  22 525-542
• 23 Chen A FY, O'Brien T, Katusic Z S. Transfer and expression of recombinant nitric oxide synthase genes in the cardiovascular system.  TiPS. 1998;  19 276-286
• 24 von der Leyen H E, Gibbons G H, Morishita R, Lewis N P, Zhang L, Nakajiama M, et al. Gene therapy inhibiting neointimal vascular lesion: In vivo transfer of endothelial cell nitric oxide synthase gene.  Proc Natl Acad Sci USA. 1995;  92 1137-1141
• 25 Waugh J M, Kattash M, Yuksel E, Kuo M D, Lussier M, et al. Gene therapy to promote thromboresistance: Local overexpression of tissue plasminogene activator to prevent arterial thrombosis in an in vivo rabbit model.  Proc Natl Acad Sci. 1999;  96 1065-1070
• 26 Gunn J, Holt C M, Francis S E, Sheperd L, Grohmann M, Newman C MH, et al. The effect of oligonucleotides to c-myb on vascular smooth muscle cell proliferation and neointima formation after porcine coronary angioplasty.  Circ Res. 1997;  80 520-531
• 27 Husain M, Simons M. Vascular antisense therapy directed against c-myc, c-myb and PCNA. In: Rabbani LE (ed) Applications of antisense therapies to restenosis. Boston; Kluwer 1999: 71-98
• 28 Kutryk M, et al. Feasibility of the local delivery of antisense oligonucleotide against c-myc for the prevention of in-stent restenosis.  Europ Heart J. 1997;  18 ( abstract) 507
• 29 Abigail K H, Fox J C, Neschis D G, Saford S D, Swain J L, Golden M A. Antisense basic fibroblast growth factor gene transfer reduces neointimal thickening after arterial injury.  J Vasc Surg. 1997;  25 320-325
• 30 Morishita R, et al. A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle cell proliferation in vivo.  Proc Natl Acad Sci USA. 1995;  92 5855-5859
• 31 Morishita R, et al. In vivo transfection of cis element decoy against NF-kB binding site prevented myocardial infarction as gene therapy.  Nat Med. 1997;  3 894-899
• 32 Smith R C, Wills K N, Antelman D, Perlman H, Truong L N, Krasinski K, et al. Adenoviral constructs encoding phosphorylation-competent full-length and truncated forms of the human retinoblastoma protein inhibit myocyte proliferation and neointima formation.  Circulation. 1997;  96 1899-1905
• 33 Indolfi C, Chiariello M, Avvedimento E V. Selective gene therapy for proliferative disorder: Sense and antisense.  Nat Med. 1996;  2 634-635
• 34 Ohno T, Gordon D, San H, Pompili V J, Imperiale M J, Nabel G J, et al. Gene therapy for vascular smooth muscle cell proliferation after arterial injury.  Science. 1994;  265 781-784
• 35 Isner J M, Pieczek A, Schainfield . et al . Clinical evidence of angiogenesis after arterial gene transfer of pHVEGF165 in patients with ischemic limb.  Lancet. 1996;  348 370-374
• 36 Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia.  Circulation. 1998;  97 1114-1123
• 37 Voss S D, Kruskal J B. Gene therapy: A primer for radiologists.  RadioGraphics. 1998;  18 1343-1372
• 38 Gonschior P, Wilensky R, March K, Hofling B. Lokale Medikamentenapplikationssysteme, präklinische und klinische Anwendung: Perspektiven und Limitationen.  Z Kardiol. 1996;  85 155-165
• 39 Roth J A, Nguyen D, Lawrence D D, et al. Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer.  Nat Med. 1996;  2 985-991
• 40 Hallahan D E, Mauceri H J, Seung L P, Dunphy E J, Wayne J D, Hanna N N, et al. Spatial and temporal control of gene therapy using ionizing radiation.  Nat Med. 1995;  1 786-791