Einfluss molekularbiologischer Verfahren auf nuklearmedizinische Methoden

Zusammenfassung

Die Ergebnisse der Grundlagenforschung liefern Informationen über viele neue molekulare Strukturen, die als potenzielle neue diagnostische oder therapeutische Zielstrukturen dienen können. Die Selektion und Evaluation dieser Zielstrukturen wird Informationen über Physiologie, Biochemie und Pharmakologie benötigen. Diese Informationen können zum Teil durch nuklearmedizinische Methoden erhalten werden. So können nuklearmedizinische Verfahren zur Bestimmung der Funktion und Regulation von Genen eingesetzt werden. Die Pharmakogenomik wird neue Surrogatmarker für die Verlaufsbeobachtung von Therapien identifizieren, die mögliche neue Radiotracer darstellen. Neue Therapieansätze benötigen Bioverteilungsstudien in präklinischen Stadien und Verfahren zur Beurteilung ihrer Effizienz. Schließlich können biotechnologische Verfahren wie Phagen-Display zur Entwicklung neuer Biomoleküle für die isotopenbasierte Diagnostik und Therapie eingesetzt werden [127].

Abstract

Basic research delivers information concerning new molecular structures with potential use as target structures for diagnosis and therapy with further need for selection and evaluation by the methods of physiology, biochemistry and pharmacology using in part nuclear medical techniques for estimation of gene function and regulation. Pharmacogenomic will identify new surrogate markers as potential new radiotracers for follow-up of therapies. New therapeutical approaches will need biodistribution studies in the preclinical stage and techniques for evaluation of efficiency. At least, biotechnological techniques such as phage display may be suitable to develop new biomolecules for isotope related diagnostics and therapy.

Schlüsselwörter

Molekularbiologie - Antisense-Moleküle - Suizid-Gene - Iodidspeicherung - MIBG-Speicherung - Gentherapie

Key words

Molecular imaging - gene therapy - gene expression - peptides

Literatur

• 1 Zamecnik P C, Stephenson M L. Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide.  Proc Natl Acad Sci USA. 1978;  75 280-285
• 2 Mukhopadhyay T, Tainsky M, Cavender A C, Roth J A. Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA.  Cancer Res. 1991;  51 1744-1748
• 3 Hannon G J. RNA interference.  Nature. 2002;  418 244-251
• 4 Zeng Y. et al . Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells.  Mol Cell. 2002;  9 1327-1333
• 5 Sui G. et al . A DNA vector-based RNAi technology to suppress gene expression in mammalian cells.  Proc Natl Acad Sci USA. 2002;  99 5515-5520
• 6 Moss E G. Silencing unhealthy alleles naturally.  Trends Biotechnol. 2003;  21 185-187
• 7 Claverie J M. What if there are only 30 000 human genes?.  Science. 2001;  291 1255-1257
• 8 Woolf T M, Melton D A, Jennings C GB. Specificity of antisense oligonucleotides in vivo.  Proc Natl Acad Sci USA. 1992;  89 7305-7309
• 9 Iversen P L, Zhu S, Meyer A, Zon G. Cellular uptake and subcellular distribution of phosphorothioate oligonucleotides into cultured cells.  Antisense Res Dev. 1992;  2 211-222
• 10 Loke S L, Stein C A, Zhang X H, Mori K, Nakanishi M, Subasinghe C, Cohen J S, Neckers L M. Characterization of oligonucleotide transport into living cells.  Proc Natl Acad Sci USA. 1989;  86 3474-3478
• 11 Dewanjee M K, Ghafouripour A K, Kapadvanjwala M, Dewanjee S, Serafini A N, Lopez D M, Sfakianakis G N. Noninvasive imaging of c-myc oncogene messenger RNA with indium-111-antisense probes in a mammary tumor-bearing mouse model.  J Nucl Med. 1994;  35 1054-1063
• 12 Cammilleri S, Sangrajrang S, Perdereau B, Brixy F, Calvo F, Bazin H, Magdelenat H. Biodistribution of iodine-125 tyramine transforming growth factor? Antisense oligonucleotide in athymic mice with a human mammary tumor xenograft following intratumoral injection.  Eur J Nucl Med. 1996;  23 448-452
• 13 Kobori N, Imahori Y, Mineura K, Ueda S, Fujii R. Visualization of mRNA expression in CNS using ¹¹C-labeled phosphorothioate oligodeoxynucleotide.  Neuroreport. 1999;  10 2971-2974
• 14 Shi N, Boado R J, Pardridge W M. Antisense imaging of gene expression in the brain in vivo.  Proc Natl Acad Sci USA. 2000;  97 14709-14714
• 15 Urbain J L, Shore S K, Vekemans M C, Cosenza S C, DeRiel K, Patel G V, Charkes N D, Malmud L S, Reddy E P. Scintigraphic imaging of oncogenes with antisense probes: does it make sense?.  Eur J Nucl Med. 1995;  22 499-504
• 16 Tavitian B, Terrazzino S, Kühnast B, Marzabal S, Stettler O, Dolle F, Deverre J R, Jobert A, Hinnen F, Bendriem B, Crouzel C, Di Giamberardino L. In vivo imaging of oligonucleotides with positron emission tomography.  Nature Med. 1998;  4 467-471
• 17 Watanabe N, Sawai H, Endo K, Shinozuka K, Ozaki H, Tanada S, Murata H, Sasaki Y. Labeling of phosphorothioate antisense oligonucleotides with yttrium-90.  Nucl Med Biol. 1999;  26 239-243
• 18 Anderson L, Seilhamer J. A comparison of selected mRNA and protein abundances in human liver.  Electrophoresis. 1977;  18 533-537
• 19 Futcher B, Latter G I, Monardo P, McLaughlin C S, Garrels J I. A sampling of the yeast proteome.  Mol Cell Biol. 1999;  19 7357-7368
• 20 Gygi S P, Rist B, Gerber S A, Turecek F, Gelb M H, Aebersold R. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags.  Nat Biotechnol. 1999;  17 994-999
• 21 Schellingerhout D, Bogdanov A, Marecos E, Spear M, Breakefield X, Weissleder R. Mapping the in vivo distribution of herpes simplex virions.  Hum Gene Ther. 1998;  9 1543-1549
• 22 Zinn K R, Douglas J T, Smyth C A, Liu H G, Wu Q, Krasnykh V N, Mountz J D, Curiel D T, Mountz J M. Imaging and tissue biodistribution of ^99mTc-labeled adenovirus knob (serotype 5).  Gene Ther. 1998;  5 798-808
• 23 Caruso M, Panis Y, Gagandeep S, Houssin D, Salzmann J L, Klatzman D. Regression of established macroscopic liver metastases after in situ transduction of a suicide gene.  Proc Natl Acad Sci USA. 1993;  90 7024-7028
• 24 Chen S H, Shine H D, Goodman J C, Grossman R G, Woo S LC. Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo.  Proc Natl Acad Sci USA. 1994;  91 3054-3057
• 25 Culver K W, Ram Z, Walbridge S. et al . In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors.  Science. 1992;  256 1550-1552
• 26 Oldfield E H, Ram Z, Culver K W, Blaese R M, DeVroom H L, Anderson W F. Gene therapy for the treatment of brain tumors using intra-tumoral transduction with the thymidine kinase gene and intravenous ganciclovir.  Hum Gene Ther. 1993;  1 39-69
• 27 Keller P M, Fyfe J A, Beauchamp L. et al . Enzymatic phosphorylation of acyclic nucleoside analogs and correlations with antiherpetic activities.  Biochem Pharmacol. 1981;  30 3071-3077
• 28 Haberkorn U, Oberdorfer F, Gebert J. et al . Monitoring of gene therapy with cytosine deaminase: in vitro studies using ³H-5-fluorocytosine.  J Nucl Med. 1996;  37 87-94
• 29 Huber B E, Austin E A, Good S S, Knick V C, Tibbels S, Richards C A. In vivo antitumor activity of 5-fluorocytosine on human colorectal carcinoma cells genetically modified to express cytosine deaminase.  Cancer Res. 1993;  53 4619-4626
• 30 Mullen C A, Coale M M, Lowe R, Blaese R M. Tumors expressing the cytosine deaminase suicide gene can be eliminated in vivo with 5-fluorocytosine and induce protective immunity to wild type tumor.  Cancer Res. 1994;  54 1503-1506
• 31 Monclus M, Luxen A, Van Naemen J. et al . Development of PET radiopharmaceuticals for gene therapy: synthesis of 9-((1-(¹⁸F)fluoro-3-hydroxy-2-propoxy)methyl)guanine.  J Label Comp Radiopharm. 1995;  37 193-195
• 32 Visser G WM, Boele S, Knops G HJN, Herscheid J DM, Hoekstra A. Synthesis and biodistribution of (¹⁸F)-5-fluorocytosine.  Nucl Med Comm. 1985;  6 455-459
• 33 Bouali-Benazzouz R, Laine M, Vicat J M. et al . Therapeutic efficacy of the thymidine kinase/ganciclovir system on large experimental gliomas: a nuclear magnetic resonance imaging study.  Gene Ther. 1999;  6 1030-1037
• 34 Izquierdo M. et al . Long-term rat survival after malignant brain tumour regression by retroviral gene therapy.  Gene Ther. 1995;  2 66-69
• 35 Maron A. et al . Gene therapy of rat C6 glioma using adenovirus-mediated transfer of the Herpes Simplex Virus thymidine kinase gene: long-term follow-up by magnetic resonance imaging.  Gene Ther. 1996;  3 315-322
• 36 Ross B D, Kim B, Davidson B L. Assessment of ganciclovir toxicity to experimental intracranial gliomas following recombinant adenoviral-mediated transfer of the herpes simplex virus thymidine kinase gene by magnetic resonance imaging and proton magnetic resonance spectroscopy.  Clin Cancer Res. 1995;  1 651-657
• 37 Sobol R E. et al . Interleukin-2 gene therapy in a patient with glioblastoma.  Gene Ther. 1995;  2 164-167
• 38 Shand N, Weber F, Mariani L. et al . A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. GLI328 European-Canadian Study Group.  Hum Gene Ther. 1999;  10 2325-2335
• 39 Ram Z, Walbridge S, Shawker T, Culver K W, Blaese R M, Oldfield E H. The effect of thymidine kinase transduction and ganciclovir therapy on tumor vasculature and growth of 9L-gliomas in rats.  J Neurosurg. 1994;  81 256-260
• 40 Ram Z, Culver K, Oshiro E M. et al . Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells.  Nature Med. 1997;  3 1354-1361
• 41 Morin K W, Knaus E E, Wiebe L I, Xia H, McEwan A J. Reporter gene imaging: effects of ganciclovir treatment on nucleoside uptake, hypoxia and perfusion in a murine gene therapy tumour model that expresses herpes simplex type-1 thymidine kinase.  Nucl Med Commun. 2000;  21 129-137
• 42 Haberkorn U, Morr I, Oberdorfer F. et al . Fluorodeoxyglucose uptake in vitro: aspects of method and effects of treatment with gemcitabine.  J Nucl Med. 1994;  35 1842-1850
• 43 Haberkorn U, Bellemann M E, Altmann A, Gerlach L, Morr I, Oberdorfer F, Brix G, Doll J, Blatter J, van Kaick G. F-18-fluoro-2-deoxyglucose uptake in rat prostate adenocarcinoma during chemotherapy with 2′,2′-difluoro-2′-deoxycytidine.  J Nucl Med. 1997;  38 1215-1221
• 44 Rozenthal J M, Levine R L, Nickles R J, Dobkin J A. Glucose uptake by gliomas after treatment.  Arch Neurol. 1989;  46 1302-1307
• 45 Haberkorn U, Altmann A, Morr I. et al . Multi tracer studies during gene therapy of hepatoma cells with HSV thymidine kinase and ganciclovir.  J Nucl Med. 1997;  38 1048-1054
• 46 Haberkorn U, Bellemann M E, Gerlach L, Morr I, Trojan H, Brix G, Altmann A, Doll J, van Kaick G. Uncoupling of 2-fluoro-2-deoxyglucose transport and phosphorylation in rat hepatoma during gene therapy with HSV thymidine kinase.  Gene Ther. 1998;  5 880-887
• 47 Clancy B M, Czech M P. Hexose transport stimulation and membrane redistribution of glucose transporter isoforms in response to cholera toxin, dibutyryl cyclic AMP, and insulin in 3T3 adipocytes.  J Biol Chem. 1990;  265 12434-12443
• 48 Wertheimer E, Sasson S, Cerasi E, Ben-Neriah Y. The ubiquitous glucose transporter GLUT-1 belongs to the glucose-regulated protein family of stress-inducible proteins.  Proc Natl Acad Sci USA. 1991;  88 2525-2529
• 49 Widnell C C, Baldwin S A, Davies A, Martin S, Pasternak C A. Cellular stress induces a redistribution of the glucose transporter.  FASEB J. 1990;  4 1634-1637
• 50 Haberkorn U, Altmann A, Morr I. et al . Gene therapy with Herpes Simplex Virus thymidine kinase in hepatoma cells: uptake of specific substrates.  J Nucl Med. 1997;  38 287-294
• 51 Saito Y, Price R, Rottenberg D A, Fox J J, Su T L, Watanabe K A, Philipps F A. Quantitative autoradiographic mapping of herpes simplex virus encephalitis with radiolabeled antiviral drug.  Science. 1982;  217 1151-1153
• 52 Germann C, Shields A F, Grierson J R, Morr I, Haberkorn U. 5-Fluoro-1-(2′-deoxy-2′-fluoro-β-D-ribofuranosyl)uracil trapping in Morris hepatoma cells expressing the Herpes Simplex Virus thymidine kinase gene.  J Nucl Med. 1998;  39 1418-1423
• 53 Haberkorn U, Khazaie K, Morr I, Altmann A, Müller M, van Kaick G. Ganciclovir uptake in human mammary carcinoma cells expressing Herpes Simplex Virus thymidine kinase.  Nucl Med Biol. 1998;  25 367-373
• 54 Bi W L, Parysk L M, Warnick R, Stambrook P J. In vitro evidence that metabolic cooperation is responsible for the bystander effect observed with HSV-tk retroviral gene therapy.  Hum Gene Ther. 1993;  4 725-731
• 55 Freeman S M, Abbond C N, Whartenby K A. et al . The “bystander effect”: tumor regression when a fraction of tumor mass is genetically modified.  Cancer Res. 1993;  53 5274-5283
• 56 Chen C Y, Chang Y N, Ryan P, Linscott M, McGarrity G J, Chiang Y L. Effect of Herpes Simplex Virus thymidine kinase expression levels on ganciclovir-mediated cytotoxicity and the “bystander effect”.  Hum Gene Ther. 1995;  6 1467-1476
• 57 Haberkorn U. Monitoring of gene transfer for cancer therapy with radioactive isotopes.  Ann Nucl Med. 1999;  13 369-377
• 58 Alauddin M M, Shahinian A, Kundu R K, Gordon E M, Conti P S. Evaluation of 9-[(3-¹⁸F-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([¹⁸F]-FHPG) in vitro and in vivo as a probe for PET imaging of gene incorporation and expression in tumors.  Nucl Med Biol. 1999;  26 371-376
• 59 Alauddin M M, Conti P S. Synthesis and preliminary evaluation of 9-(4-[¹⁸F]-fluoro-3-hydroxymethylbutyl)guanine ([¹⁸F]FHBG): a new potential imaging agent for viral infection and gene therapy using PET.  Nucl Med Biol. 1998;  25 175-180
• 60 de Vries E F, van Waarde A, Harmsen M C, Mulder N H, Vaalburg W, Hospers G A. [¹¹C]FMAU and [¹⁸F]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections.  Nucl Med Biol. 2000;  27 113-119
• 61 Gambhir S S, Barrio J R, Phelps M E, Iyer M, Namavari M, Satyamurthy N, Wu L, Green L A, Bauer E, MacLaren D C, Nguyen K, Berk A J, Cherry S R, Herschman H R. Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography.  Proc Natl Acad Sci USA. 1999;  96 2333-2338
• 62 Gambhir S S, Bauer E, Black M E. et al . A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography.  Proc Natl Acad Sci USA. 2000;  97 2785-2790
• 63 Haubner R, Avril N, Hantzopoulos P A, Gansbacher B, Schwaiger M. In vivo imaging of herpes simplex virus type 1 thymidine kinase gene expression: early kinetics of radiolabelled FIAU.  Eur J Nucl Med. 2000;  27 283-291
• 64 Hustinx R, Shiue C Y, Alavi A, McDonald D, Shiue G G, Zhuang H, Lanuti M, Lambright E, Karp J S, Eck S. Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and (¹⁸F)FHPG.  Eur J Nucl Med. 2001;  28 5-12
• 65 Iwashina T, Tovell D R, Xu L, Tyrrell D L, Knaus E E, Wiebe L I. Synthesis and antiviral activity of IVFRU, a potential probe for the non-invasive diagnosis of Herpes Simplex encephalitis.  Drug Design and Delivery. 1988;  3 309-321
• 66 Morin K W, Knaus E E, Wiebe L I. Non-invasive scintigraphic monitoring of gene expression in a HSV-1 thymidine kinase gene therapy model.  Nucl Med Commun. 1997;  18 599-605
• 67 Tjuvajev J G, Stockhammer G, Desai R, Uehara H, Watanabe K, Gansbacher B, Blasberg R G. Imaging the expression of transfected genes in vivo.  Cancer Res. 1995;  55 6126-6132
• 68 Tjuvajev J G. et al . Noninvasive imaging of Herpes Simplex Virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy.  Cancer Res. 1996;  56 4087-4095
• 69 Wiebe L I, Morin K W, Knaus E E. Radiopharmaceuticals to monitor gene transfer.  Q J Nucl Med. 1997;  41 79-89
• 70 Wiebe L I, Knaus E E, Morin K W. Radiolabelled pyrimidine nucleosides to monitor the expression of HSV-1 thymidine kinase in gene therapy.  Nucleosides Nucleotides. 1999;  18 1065-1066
• 71 Yu Y, Annala A J, Barrio J R. et al . Quantification of target gene expression by imaging reporter gene expression in living animals.  Nature Med. 2000;  6 933-937
• 72 Arturi F, Russo D, Schlumberger M. et al . Iodide symporter gene expression in human thyroid tumors.  J Clin Endocrinol Metab. 1998;  83 2493-2496
• 73 Caillou B, Troalen F, Baudin E, Talbot M, Filetti S, Schlumberger M, Bidart J M. Na⁺/I-symporter distribution in human thyroid tissues: an immunohistochemical study.  J Clin Endocrinol Metab. 1998;  83 4102-4106
• 74 Cho J Y, Sagartz J E, Capen C C, Mazzaferri E L, Jhiang S M. Early cellular abnormalities induced by RET/PTC1 oncogene in thyroid-targeted transgenic mice.  Oncogene. 1999;  18 3659-3665
• 75 Lazar V, Bidart J M, Caillou B, Mahe C, Lacroix L, Filetti S, Schlumberger M. Expression of the Na+/I-symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes.  J Clin Endocrinol Metab. 1999;  84 3228-3234
• 76 Ryu K Y, Senokozlieff M E, Smanik P A. et al . Development of reverse transcription-competitive polymerase chain reaction method to quantitate the expression levels of human sodium iodide symporter.  Thyroid. 1999;  9 405-409
• 77 Haberkorn U, Henze M, Altmann A, Jiang S, Morr I, Mahmut M, Peschke P, Debus J, Kübler W, Eisenhut M. Transfer of the human sodium iodide symporter gene enhances iodide uptake in hepatoma cells.  J Nucl Med. 2001;  42 317-325
• 78 Shimura H, Haraguchi K, Miyazaki A, Endo T, Onaya T. Iodide uptake and experimental ¹³¹J therapy in transplanted undifferentiated thyroid cancer cells expressing the Na⁺/I-symporter gene.  Endocrinology. 1997;  138 4493-4496
• 79 Smanik P A, Liu Q, Furminger T L, Ryu K, Xing S, Mazzaferri E L, Jhiang S M. Cloning of the human sodium iodide symporter.  Biochem Biophys Res Commun. 1996;  226 339-345
• 80 Boland A, Ricard M, Opolon P, Bidart J M, Yeh P, Filetti S, Schlumberger M, Perricaudet M. Adenovirus-mediated transfer of the thyroid sodium/Iodide symporter gene into tumors for a targeted radiotherapy.  Cancer Res. 2000;  60 3484-3492
• 81 Cho J Y, Xing S, Liu X, Buckwalter T LF, Hwa L, Sferra T J, Chiu I M, Jhiang S M. Expression and activity of human Na⁺/I-symporter in human glioma cells by adenovirus-mediated gene delivery.  Gene Ther. 2000;  7 740-749
• 82 Mandell R B, Mandell L Z, Link C J. Radioisotope concentrator gene therapy using the sodium/iodide symporter gene.  Cancer Res. 1999;  59 661-668
• 83 Spitzweg C, Zhang S, Bergert E R. et al . Prostate-specific antigen (PSA) promoter-driven androgen-inducible expression of sodium iodide symporter in prostate cancer cell lines.  Cancer Res. 1999;  59 2136-2141
• 84 Haberkorn U, Kinscherf R, Kissel M. et al . Enhanced iodide transport after transfer of the human sodium iodide symporter gene is associated with lack of retention and low absorbed dose.  Gene Ther. 2003;  10 774-780
• 85 Haberkorn U, Beuter P, Kübler W, Eskerski H, Eisenhut M, Kinscherf R, Zitzmann S, Strauss L G, Dimitrakopoulou-Strauss A, Altmann A. Iodide kinetics and dosimetry in vivo after transfer of the human sodium iodide symporter gene in rat thyroid carcinoma cells.  J Nucl Med. 2004;  45 827-833
• 86 Haberkorn U, Altmann A, Jiang S. et al . Iodide uptake in human anaplastic thyroid carcinoma cells after transfer of the human thyroid peroxidase gene.  Eur J Nucl Med. 2001;  28 633-638
• 87 Guo J, McLachlan S M, Hutchinson S, Rapoport B. The greater glycan content of recombinant human thyroid peroxidase of mammalian than of insect cell origin facilitates purification to homogeneity of enzymatically protein remaining soluble at high concentration.  Endocrinology. 1998;  139 999-1005
• 88 Hidaka Y, Hayashi Y, Fisfalen M E, Suzuki S, Takeda T, Refetoff S, DeGroot L J. Expression of thyroid peroxidase in EBV-transformed B cell lines using adenovirus.  Thyroid. 1996;  6 23-28
• 89 Kaufman K D, Filetti S, Seto P, Rapoport B. Recombinant human thyroid peroxidase generated in eukaryotic cells: a source of specific antigen for the immunological assay of antimicrosomal antibodies in the sera of patients with autoimmune thyroid disease.  J Clin Endocrinol Metab. 1990;  70 724-728
• 90 Kimura S, Kotani T, Ohtaki S, Aoyama T. cDNA-directed expression of human thyroid peroxidase.  FEBS letters. 1989;  250 377-380
• 91 Giraud A, Franc J L, Long Y, Ruf J. Effects of deglycosylation of human thyroperoxidase on its enzymatic activity and immunoreactivity.  J Endocrinol. 1992;  132 317-323
• 92 Giraud A, Siffroi S, Lanet J, Franc J L. Binding and internalization of thyroglobulin: selectivity, pH dependence, and lack of tissue specificity.  Endocrinology. 1997;  138 2325-2332
• 93 Ohtaki S, Nakagawa H, Nakamura M, Kotani T. Thyroid peroxidase: experimental and clinical integration.  Endocrine J. 1996;  43 1-14
• 94 Ohtaki S, Kotani T, Nakamura Y. Characterization of human thyroid peroxidase purified by monoclonal antibody-assisted chromatography.  J Clin Endocrinol Metab. 1986;  63 570-576
• 95 Taurog A, Dorris M L, Yokoyama N, Slaughter C. Purification and characterization of a large, tryptic fragment of human thyroid peroxidase with high catalytic activity.  Arch Biochem Biophys. 1990;  278 333-341
• 96 Smets L A, Loesberg C, Janssen M, Metwally E A, Huiscamp R. Active uptake and extravesicular storage of m-iodobenzyl guanidine in human neuroblastoma.  Cancer Res. 1989;  49 2941-2944
• 97 Wafelman A R, Hoefnagel C A, Maes R AA, Beijnen J H. Radioiodinated metaiodo-benzylguanidine: a review of its distribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry.  Eur J Nucl Med. 1994;  21 545-559
• 98 Mairs R J, Livingstone A, Gaze M N, Wheldon T E, Barrett A. A Prediction of accumulation of ¹³¹I-labelled meta-iodobenzylguanidine in neuroblastoma cell lines by means of reverse transcription and polymerase chain reaction.  Br J Cancer. 1994;  70 97-101
• 99 Glowniak J V, Kilty J E, Amara S G, Hoffman B J, Turner F E. Evaluation of metaiodobenzylguanidine uptake by the norepinephrine, dopamine and serotonin transporters.  J Nucl Med. 1993;  34 1140-1146
• 100 Lode H N, Bruchelt G, Seitz G. et al . Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of monoamine transporters in neuroblastoma cell lines: correlations to meta-iodobenzylguanidine (MIBG) uptake and tyrosine hydroxylase gene expression.  Eur J Cancer. 1995;  31 586-590
• 101 Pacholczyk T, Blakely R D, Amara S G. Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter.  Nature. 1991;  350 350-354
• 102 Boyd M, Cunningham S H, Brown M M, Mairs R J, Wheldon T E. Noradrenaline transporter gene transfer for radiation cell kill by ¹³¹I meta-iodobenzylguanidine.  Gene Ther. 1999;  6 1147-1152
• 103 Altmann A, Kissel M, Zitzmann S. et al . Increased MIBG uptake after transfer of the human norepinephrine transporter gene in rat hepatoma.  J Nucl Med. 2003;  44 973-980
• 104 Bomanji J, Levison D A, Flatman W D. et al . Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison.  J Nucl Med. 1987;  28 973-978
• 105 Petrich T. et al . Establishment of radioactive astatine and iodine uptake in cancer cell lines expressing the human sodium iodide symporter.  Eur J Nucl Med. 2002;  29 842-854
• 106 Reubi J C, Schaer J C, Waser B, Menod G. Expression and localization of somatostatin receptor SSTR1, SSTR2 and SSTR3 messenger RNAs in primary human tumors using in situ hybridization.  Cancer Res. 1994;  54 3455-3459
• 107 Pless J, Bauer W, Briner U. et al . Chemistry and pharmacology of SMS 201-005, a long-acting analog of somatostatin.  Scand J Gastroenterol. 1986;  2 54-64
• 108 Kvols L K, Moertel C G, O'Connel M J. et al . Treatment of malignant carcinoid syndrome: evaluation of a long-acting somatostatin analog.  N Engl J Med. 1986;  315 663-666
• 109 Bakker W H, Albert R, Bruns C. et al . [¹¹¹In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation.  Life Sci. 1991;  49 1583-1591
• 110 Krenning E P, Kwekkeboom D J, Reubi J C. et al . ¹¹¹In-octreotide scintigraphy in oncology.  Metabolism. 1992;  41 83-86
• 111 Lamberts S WJ, Krenning E P, Reubi J C. The role of somatostatin and its analogs in the diagnosis and treatment of tumors.  Endocrine Rev. 1991;  19 450-482
• 112 Pallela V R, Thakur M L, Chakder S, Rattan S. ^99mTc-labeled vasoactive intestinal peptide receptor agonist: functional studies.  J Nucl Med. 1999;  40 352-360
• 113 Raderer M, Kurtaran A, Yang Q. et al . Iodine-123-vasoactive intestinal peptide receptor scanning in patients with pancreatic cancer.  J Nucl Med. 1998;  39 1570-1575
• 114 Virgolini I, Raderer M, Kurtaran A. et al . Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors.  N Engl J Med. 1994;  331 1116-1121
• 115 Behr T M, Jenner N, Radetzky S, Behe M, Gratz S, Yucekent S, Raue F, Becker W. Targeting of cholecystokinin-B/gastrin receptors in vivo: preclinical and initial clinical evaluation of the diagnostic and therapeutic potential of radiolabelled gastrin.  Eur J Nucl Med. 1998;  25 424-430
• 116 Breeman W A, Hofland L J, de Jong M. et al . Evaluation of radiolabelled bombesin analogues for receptor-targeted scintigraphy and radiotherapy.  Int J Cancer. 1999;  81 658-665
• 117 Rogers B E, Rosenfeld M E, Khazaeli M B. et al . Localization of iodine-125-mIP-Des-Met14-bombesin (7-13)NH2 in ovarian carcinoma induced to express the gastrin releasing peptide receptor by adenoviral vector-mediated gene transfer.  J Nucl Med. 1997;  38 1221-1229
• 118 Yamada K M. Adhesive recognition sequences.  J Biol Chem. 1991;  266 12809-12812
• 119 Humphries M J, Yamada K M, Olden K. Investigation of the biological effects of anti-cell adhesive synthetic peptides that inhibit experimental metastasis of B16-F10 murine melanoma cells.  J Clin Invest. 1988;  81 782-790
• 120 Nowlin D M, Gorcsan F, Moscinski M. et al . A novel cyclic pentapeptide inhibits alpha 4 beta 1 and alpha 5 beta 1 integrin-mediated cell adhesion.  J Biol Chem. 1993;  268 20352-20359
• 121 Haubner R, Wester H J, Reuning U. et al . Radiolabeled alpha(v)beta3 integrin antagonists: a new class of tracers for tumor targeting.  J Nucl Med. 1999;  40 1061-1071
• 122 Haubner R, Wester H J, Burkhart F, Senekowitsch-Schmidtke R, Weber W, Goodman S L, Kessler H, Schwaiger M. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics.  J Nucl Med. 2001;  42 326-336
• 123 Haubner R, Wester H J, Weber W A. et al . Noninvasive imaging of alpha(v)beta3 integrin expression using ¹⁸F-labeled RGD-containing glycopeptide and positron emission tomography.  Cancer Res. 2001;  61 1781-1785
• 124 Pasqualini R, Koivunen E, Ruoslahti E. Alpha v integrins as receptors for tumor targeting by circulating ligands.  Nat Biotechnol. 1997;  15 542-546
• 125 Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model.  Science. 1998;  279 377-380
• 126 Zitzmann S, Mier W, Schad A, Kinscherf R, Askoxylakis V, Krämer S, Altmann A, Eisenhut M, Haberkorn U. A new prostate carcinoma binding peptide (DUP-1) for tumor imaging and therapy.  Clin Cancer Research. im Druck; 
• 127 Zitzmann S, Krämer S, Mier W, Mahmut M, Fleig J, Altmann A, Eisenhut M, Haberkorn U. Identification of a new prostate specific cyclic peptide with the bacterial FLITRX system.  J Nucl Med. im Druck; 
• 128 Haberkorn U, Altmann A, Eisenhut M. Functional genomics and proteomics - the role of nuclear medicine.  Eur J Nuc Med. 2002;  29 115-132