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The development of new radiopharmaceuticals

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Abstract

The development of new radiopharmaceuticals is the basis of the continuing growth of nuclear medicine. Chemical interactions of electron clouds in their three dimensional conformations bring together, in the process of molecular recognition, the reaction of antibody and antigen, receptor and ligand, enzyme and substrate, hormone and response site. This convergence enables the computer design of molecules such as ligands to fit computer-displayed conformational models showing active centres, positive and negative charges and other interactions. Indeed, given a particular molecule, a complementary binding structure can be devised. The hybridoma approach to monoclonal antibody production is being superceded by the bacterial bioengineer. The gene for the hypervariable region from the spleen cells of immunized mouse can be coupled with the myeloma gene. The polymerase chain reaction can duplicate the DNA a million times over in 20 min and the result transfected into a bacterial plasmid to produce the antibody. These scientific problems are soluble in principle and are being solved. However, so much damage to this developing biological field is being done by regulatory authorities that one must ask who should or can regulate the regulators. These problems have to be overcome in order to provide the new radiopharmaceuticals that are the food and wine of nuclear medicine.

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References

  • Al Nahhas A, Jafri RA, Britton KE, Solanki K, Bomanji J, Mather S, Carroll MJ, Al-Janabi M, Frusciante V, Ajdinowic B, Fiore F, Demena S, Nimmon CC (1988) Clinical experience with Te99m MAG3, mercaptoacetyl triglycine and a comparison with Tc-99m DTPA. Eur J Nucl Med 14:453–462

    Google Scholar 

  • Baillet GY, Mena IG, Kuperus JH, Robertson JM, French WJ (1989) Simultaneous technetium-99m MIBI angiography and myocardial perfusion imaging. J Nucl Med 30:38–44

    Google Scholar 

  • Baum RP, Hertel A, Lorenz M, Hottenrott C, Schwartz A, Maul FD, Hör G (1988) Tc-99m labelled intact monoclonal anti-CEA antibody for successful localisation of tumour recurrences. Proceedings of the 1st EANM Congress, Milan. Nuklearmedizin 515–518

  • Baum RP, Hertel A, Lorenz M, Schwartz A, Encke A, Hör G (1989) Tc-99m labelled anti-CEA monoclonal antibody for tumour immunoscintigraphy: first clinical results. Nucl Med Commun 10:345–352

    Google Scholar 

  • Blake GM, Grey JM, Zivanovic MA, McEwan AJ, Fleming JS, Aekery DM (1987) Strontium-89 radionuclide therapy: a dosimetric study using impulse response function analysis. Br J Radiol 60:685–692

    Google Scholar 

  • Blundell TL (1984) The design of molecules starting from protein structures. Proceeding European Seminar in Computer Aided Molecular Design. Oyez Scientific and Technical Services, London, pp 169–184

    Google Scholar 

  • Bonifce GR, Izard ME, Walker KZ, Mckay DR, Sorby PJ, Turner JH, Morris JG (1989) Labelling of monoclonal antibodies with samarium-153 for combined radioimmunoscitigraphy and radioimmunotherapy. J Nucl Med 30:683–691

    Google Scholar 

  • Boye E, Lindegaard MW, Pans E, Skretting A, Davy M, Jakobsen E (1984) Whole body distribution of radioactivity after intraperitoneal administration of P-32 colloids. Br J Radiol 57:395–402

    Google Scholar 

  • Bradley-Moore PR, Lebowitz E, Greene MW, Atkins HL, Ansari N (1975) Thallium 201 for medical use. J Nucl Med 16:156–160

    Google Scholar 

  • Britton KE (1990) Potential clinical applications of monoclonal antibodies. In: Bringing biotechnology to the market. British Institute of Regulatory Affairs, London (in press)

    Google Scholar 

  • Britton KE, Granowska M (1987) Radioimmunoscintigraphy in tumour identification. Cancer Surv 6:247–267

    Google Scholar 

  • Britton KE, Granowska M, Mather S (1985) Experience with 123-I labelled monoclonal antibodies. In: Donato L, Britton KE (eds) Monographs in nuclear medicine, vol 1. Immunoscintigraphy. Gordon & Breach, London, pp 55–66

    Google Scholar 

  • Buraggi GL, Turrin A, Cascinelli N, Ferrone S, Callegaro L, Attili A, Bombardieri E, Gasparini M, Seregni E, Belli F (1985) Proceedings of the 23rd SNME/ENMS Congress, London. Nuklearmedizin 421–423

  • Burch WM, Fawdry RG, Tetley IJ, Sullivan PJ, Lomas FE (1985) Technegas - the ideal lung ventilation agent? Procedings of the 23rd SNME/ENMS Congress, London. Nuklearmedizin 642

  • Burchell J, Gendler S, Taylor-Papadimitriou J, Girling A, Lewis A, Millis R, Lampert D (1987) Development and characterisation of breast cancer reactive monoclonal antibodies directed to the Core protein of human mucin. Cancer Res 47:5476–5482

    Google Scholar 

  • Clarke SEM, Lazarus CR, Edwards S, Roden T, Maisey MN (1986) A comparison of I-131 MIBG and Tc-99m pentavalent DMSA for imaging patients with medullary carcinoma of the thyroid. Proceedings of the 23rd SNME/ENMS Congress, Goslar. Nuklear Medizin 475–476

  • Coakley AJ, Kettle AG, Wells CP, O'Doherty MJ, Collins REC (1989) Tc-99m sestambibi - a new agent for parathyroid imaging. Nucl Med Commun 10:791–794

    Google Scholar 

  • Costa DC, Lui D, Sinha AK, Jarritt PH, Ell PJ (1989) Intracellular utilisation of Tc-99m d.1. HMPAO and TI-201 DDC in rat brain. Nucl Med Commun 10:459–466

    Google Scholar 

  • Danpure HJ. Osman S, Hogg N, Cliff E, Epenetos AA, Lavender JP (1986) The clinical use of an I-123 labelled leucocyte specific monoclonal antibody to detect inflammatory lesions. Proceedings of the 23rd SNME/ENMS Congress, Goslar. Nuklearmedizin 492–494

  • Deutsch E, Glavan KA, Sodd VJ, Nishiyama H, Ferguson DL, Lukes SJ (1981) Cationic Tc-99m complexes as potential myocardial imaging agents. J Nucl Med 22:897–907

    Google Scholar 

  • Dilworth JA, Archer CM, Latham IA, Bishop PT, Kelly JD, Higley B (1989) The synthesis of Technetium-nitride cations as potential myocardial imaging agents. J Nucl Med 30:773

    Google Scholar 

  • EEC Directive (1987) The rules governing medicaments for human use in the European Community. Council Directive of 22nd December 1986, no. L 15/38. Official Journal of the European Communities. III/182/87/87-EN 1987, p 47

  • El-Shirbiny AM, Sadek S, Owunwanne A, Yacoub T, Suresh L, Abdel-Dayem HM (1989) Is Tc-99m hexamethyl-propylene amine oxime uptake in the tissue related to glutathione cellular content. Nucl Med Commun 10:905–911

    Google Scholar 

  • Ell PJ, Hocknell L, Costa DC, Jarritt PH, Cullum I, Lui D, Nowotnik DP, Pickett RD, Neirinckx RD, Jewkes RF, Steiner TJ, Jones B (1985a). 99m-Tc-Hexamethyl propyleneamine oxime (HMPAO) - a breakthrough in radionuclide CBF tomography. Proceedings of the 23rd SNME/ENMS Congress London. Nuklearmedizin 179–181

  • Ell PJ, Hocknell JML, Jarritt PH, Cullum I, Lin D, Campo Costa D, Nowotnik DP, Pickett RD, Canning LR, Neirinckx RD (1985b) A Tc-99m labelled radiotracer for the investigation of cerebral vascular disease. Nucl Med Commun 6:437–441

    Google Scholar 

  • Epps LA, Sun L, Arevalo M, Ghrayeb J, Nedelman M, Fogler WE, Lister-James J, Dean RT (1989) Technetium (Tc-99m) labelled genetically engineered chimeric 17-1A G4K/Metallothionein antibody. J Nucl Med 30:794

    Google Scholar 

  • Evans G, Hilson AJW, Hobbs KEF (1985) Tc-99m bromotrimethyl HIDA: a clinical assessment. Proceedings of the 23rd SNME/ENMS Congress, London. Nuklearmedizin 310–312

  • Foxwell BMJ, Band HA, Long J, Jeffrey WA, Snook D, Thorpe PE, Watson G, Parker PJ, Epenetos AA, Creighton AM (1988) Conjugation of monoclonal antibodies to a synthetic peptide substitute for protein kinase: a method of labelling antibodies with P-32. Br J Cancer 57:489–493

    Google Scholar 

  • Gerundini P, Maffloli L (1989) Cationic complexes of technetium for myocardial imaging. J Nucl Med 30:1415–1419

    Google Scholar 

  • Glen RC (1984) Computer aided molecular modelling at the Wellcome Foundation. In: Computer aided molecular design. Oyez Scientific and Technical Services, London, pp 23–48

    Google Scholar 

  • Granowska M, Shepherd J, Mather S, Carroll MJ, Flatman WD, Nimmon CC, Taylor-Papadimitriou J, Ward B, Horne T, Britton KE (1984a) A prospective study of radioimmunoscintigraphy with I-123 monoclonal antibody in 26 patients with suspected ovarian cancer. Proceedings of the 22nd SNME/ENMS Congress, Helsinki. Nuklearmedizin 633–636

  • Granowska M, Shepherd J, Britton KE, Ward B, Mather S, Taylor-Papadimitriou J, Epenetos AA, Carroll MJ, Nimmon CC, Hawkins LA, Slevin M, Flatman W, Horne T, Burchell J, Durbin N, Bodmer W (1984b) Ovarian cancer diagnosis using 123-I monoclonal antibody in comparison with surgical findings. Nucl Med Commun 5:485–499

    Google Scholar 

  • Granowska M, Britton KE, Jass JR, Northover JMA, Bomanji J, Bingham L, Todd IP (1987) A prospective study of In-111 anticarcinoembryonic antigen, CEA, in colorectal cancer. Proceedings of the 24th SNME/ENMS Congress, Budapest. Nuklearmedizin 594–596

  • Granowska M, Jass JR, Britton KE, Northover JMA (1989a) A prospective study of the use of 111-In labelled monoclonal antibody against carcinoembryonic antigen in colorectal cancer and of some biological factors affecting its uptake. Int J Colorect Dis: 97–108

  • Granowska M, Mather SJ, Britton KE, Bentley SJ, Richman P, Szilvasi I, Sobnack R, Phillips RKS, Northover JMA (1989b) A Tc-99m labelled monoclonal antibody, PR1A3, for radioimmunoscintigraphy, RIS of colorectal cancer. J Nucl Med 30:748

    Google Scholar 

  • Granowska M, Mather SJ, Britton KE, Bentley S, Richman P, Phillips RKS, Northover JMA (1990a) Tc-99m radioimmunoscintigraphy of colorectal cancer. Br J Cancer (in press)

  • Granowska M, Jobling T, Britton KE, Mather SJ, Naeem M, Shepherd JH (1990b) Technetium-99m labelled monoclonal antibodies for radioimmunoscintigraphy of ovarian cancer. 19th International Symposium on Radioactive Isotopes in Clinical Medicine and Research, Bad Gastein (in press)

  • Guidelines on the Production and Quality Control of Monoclonal Antibodies of Murine Origin Intended for Use in Man (1988) Commission of the European Communities. Notes to applicants for marketing authorizations. Tibtech 6:G5-G8

    Google Scholar 

  • Hamlyn P, Sikora K (1983) Oncogenes. Lancet II: 326–329

    Google Scholar 

  • Hanelin L, Fritzberg A, Schroff R, Fer M, Weiden P, Breitz H, Fisher D, Axworthy D, Ratliff B, Vanderheyden J-L, Appelbaum J, Morgan C, Abrams P (1989) Preliminary clinical evaluation of Re-186 labelled NR-CO-02 anti-CEA F(ab')2 antibody fragment as a potential radioimmunotherapeutic agent. J Nucl Med 30:779

    Google Scholar 

  • Hawkins PN, Myers MJ, Lavender JP, Pepys MB (1988) Diagnostic radionuclide imaging of amyloid biological targetting by circulating human serum amyloid P component. Lancet I:1413–1418

    Google Scholar 

  • Hnatowich DJ, Virzi F, Doherty PW (1985) DPTA-coupled antibodies labelled with Yttrium-90. J Nucl Med 25:503–509

    Google Scholar 

  • Hnatowich DJ, Chinol M, Gionet M, Siebecker DA, Rusckowski M, Hunter R, Griffin T (1988) Yttrium-90 labelled antibodies for radioimmunotherapy: pilot studies in patients. Proceedings of the 1st EANM Congress, Milan. Nuklearmedizin 655–658

  • Horne T, Hawkins LA, Carroll ML Granowska M, Bomanji J, Britton KE (1984) 123-1 meta-iodobenzyl guanidine: synthesis and imaging the adrenal medulla and phaeochromocytoma. Proceedings of the 22nd SNME/ENMS Congress, Helsinki. Nuklearmedizin 671–674

  • Horne T, Granowska M, Dicks-Mireaux C, Hawkins LA, Britton KE, Mather SJ, Bomanji J, Kemshead JT, Kingston J, Malpas JS (1985) Neuroblastoma imaged with I-123 metaiodobenzylquanidine and with I-123 labelled monoclonal antibody UJ13A against neural tissue. Br J Radiol 58:476–480

    Google Scholar 

  • Jafri RA, Nimmon CC, Britton KE, Al-Nahhas A, Bomanji J, Solanki K, Fettich J, Hawkins LA (1987) Tc-99m MAG3, a clinical trial in nephrological disorders. Proceedings of the SNME/ENMS congress, Budapest. Nuklearmedizin 459–462

  • Jafri RA, Britton KE, Nimmon CC, Solanki K, Al Nahhas A, Bomanji J, Fettich J, Hawkins LA (1988) Tc-99m MAG3, a comparison with I-123 and I-131 orthoiodohippurate in patients with renal disorder. J Nucl Med 29:147–158

    Google Scholar 

  • Kelly JD, Higley B, Archer CM, Latham IA, Webber P, Edwards PG, Griffiths DV, Lahiri A, Chiu KW, Edwards B (1989) New functionalised diphosphine complexes for Tc-99m for myocardial perfusion imaging. J Nucl Med 30:773

    Google Scholar 

  • Kemp BE, Graves DJ, Benjamini E (1976) Synthetic peptide substitutes of the C-AMP dependent protein kinase. Fed Proc 35:1384

    Google Scholar 

  • Khalil M, Patel K, Early M, Hartley G, Thornback J, Berry J, Hubner P (1985) The use of Tc-99m tertiary butyl isonitrile BIN as a myocardial imaging agent in man. Proceedings of the 23rd SNME/ENMS Congress, London. Nuklearmedizin 73–76

  • Khaw BA, Strauss HLS, Moore R (1987) Myocardial damage delineated by In-111 antimyosin Fab and technetium 99m pyrophosphate. J Nucl Med 28:76–82

    Google Scholar 

  • Krenning EP, Bakker WH, Breeman WAP, Koper JW, Kooij PPM, Ansema L, Lameris JS, Reubi JC, Lamberts SWJ (1989) Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet I:242–244

    Google Scholar 

  • Kung HF, Pan S, Kung M-P, Billings J, Kasliwal R, Reilly J, Alavi A (1989) In vitro and in vivo evaluation of I-123 IBZM, a potential CNS DL dopamine receptor imaging agent. J Nucl Med 30:88–92

    Google Scholar 

  • Lahiri A, Highley B, Crawley JCW, Chiu KW, Edwards B, Smith T, Griffiths DV, Archer CM, Latham IA, Kelly JD (1989) Novel functionalised diphosphine complexes of Tc-99m for myocardial imaging in man. J Nucl Med 30:818

    Google Scholar 

  • Lavender JP, Roddie ME, Peters AM, Danpure HJ, Osman S, Carroll MJ, Neirinckx RD (1987) Preliminary clinical experience with Tc-99m HMPAO for labelling leucocytes and imaging inflammation. Proceedings of the 25th SNME/ENMS Congress, Budapest. Nuklearmedizin 481–482

  • Lerner RA, Tramontano A (1988) Catalytic anitbodies. Sci Am 3:52–50

    Google Scholar 

  • Marshall GR (1984) Computer aided drug design. Proceedings of the European Seminar in Computer Aided Molecular Design. Oyez Scientific and Technical Services, London, pp 3–21

    Google Scholar 

  • Mather SJ, Ellison D (1990) Reduction mediated technetium 99m labelling of monoclonal antibodies. J Nucl Med (in press)

  • Maxon HR, Thomas SR, Hertzberg VS, Schroder LE, Deutsch EA, Libson KF, Samaratunga RC, Williams CC, Moulton JS (1989) 186-Re (Sn)-HEDP palliation of painful skeletal metastases from hormonally resistant prostatic cancer. J Nucl Med 30:837

    Google Scholar 

  • Minor P (1990) Virological contamination of biotechnology products. In: Bringing biotechnology to the market. Proceedings of the Symposium on British Institute of Regulatory Affairs, 1989, London (in press)

  • Mousa SA, Maina M, Brown BA (1987) RP30 in the heart may be due to binding to a cytosolic protein. J Nucl Med 28:619

    Google Scholar 

  • Neirinckx RD, Harrison RC, Foster JF (1987) A model for the i vivo behaviour of Tc-99m d.1. HMPAO in man. J Nucl Med 28:559

    Google Scholar 

  • Ng Tang Fui S, Morrish NJ, Mashiter G, Keen H, Sodoyez JC, Sodoyez-Goffaux F, Maisey MN (1985) Proceedings of the 23rd SNME/ENMS Congress, London. Nuklearmedizin 517–519

  • Nosco D, Dunn J, Rogit M, Coveney J, Pilcher G, Helling D, Woulfe S, Neumann W, Strubel T, Marmion M (1989) Preparation and biodistribution of Te-99m complexes with hexadentate Schiff base ligands. J Nucl Med 30:733

    Google Scholar 

  • Notohamiprodjo G, Schmid A, Spohr G, Herzog H, Fienendegen LE (1984) Comparison of myocardial metabolism of 11-C-palmitic and 123-I-heptadecanoic acid in man. Proceedings of the 22nd SNME/ENMS Congress, Helsinki. Nuklearmedizin 233–236

  • Peters AM, Osman S, Henderson BC, Kelly JD, Danpure HD, Hawker RJ, Hodgson HL, Neirinckx RD, Lavender JP (1987) Clinical experience with Tc-99m hexamethylpropylene amine oxine for labelling leukocytes and imaging inflammation: preliminary communication. Lancet II:946–949

    Google Scholar 

  • Powell NP, McCready VR, Cronin B, Pepper J, Higley B, Burke JF, Tyrell DA (1989) Tc-99m labelled meso-HMPAO and glutathione content of human lung tumours. Nucl Med Commun 10:503–508

    Google Scholar 

  • Richards GR (1989) Computer aided molecular design. IBC Technical Services, London

    Google Scholar 

  • Richards WG (1984) Quantum mechanics in molecular design. Proceedings of the European Seminar in Computer Aided Molecular Design. Oyez Scientific and Technical Serives, London, pp 91–98

    Google Scholar 

  • Riechmann L, Clark M, Waldmann H, Winter G (1988) Reshaping human antibodies for therapy. Nature 332:323–327

    Google Scholar 

  • Rigo P, Meyers A, Lilet H, Larock MP, Cantineau R (1986) Myocardial imaging with Tc-99m MIBI : a potential thallium substitute. Proceedings of the 24th SNME/ENMS Congress, Goslar. Nuklearmedizin 483–485

  • Rodwell JD (1989) Engineering monoclonal antibodies. Nature 342:99–100

    Google Scholar 

  • Saiki RK, Gelfand DH, Stoffel S (1988) Primer directed enzymatic amplification of DNA with thermostable DNA polymerase. Science 239:487–491

    Google Scholar 

  • Schwarz A, Steinstraesser A (1987) A novel approach to Tc-99m labelled monoclonal antibodies. J Nucl Med 28:721

    Google Scholar 

  • Seybold K (1988) In vivo labelling of granulocytes using 123-I tagged antigranulocyte antibodies. Nucl Med Commun 9:745–752

    Google Scholar 

  • Siccardi AG, Buraggi GL, Callegaro L, Mariani G, Natali PG, Abbati A, Bastagno M, Caputo V, Mansi L, Masi R, Paganelli G, Riva P, Salvatore M, Sanguinetti M, Troncone L, Turco GL, Scassellati GA, Ferrone S (1986) Multicentre study of immunoscintigraphy with radiolabelled monoclonal antibodies in patients with melanoma. Cancer Res 46:4817–4822

    Google Scholar 

  • Sinzinger H, Kaliman J, Angelberger P, Fitsche P, Bergmann H, Hofer R (1986) Radiolabelled human LDL for the diagnosis of in vivo kinetics and the increased entry into the arterial wall in humans. Proceedings of the 24th SNME/ENMS Congress, Goslar. Nuklearmedizin 385–387

  • Sochor M, Ogris E, Hubert K, Pachinger O, Glogar D, Weber H, Kaindl F (1986) Infarct imaging with monoclonal antimyosin and Tc-99m pyrophosphate. Proceedings of the 23rd SNME/ENMS Congress, Goslar, Nuklearmedizin 95–97

  • Solanki KK, Mather SJ, Al Janabi M, Britton KE (1988) A rapid method for the preparation of Tc-99m hexametazine-labelled leucocytes. Nucl Med Commun 9:753–761

    Google Scholar 

  • Tubiana M (1989) Thyroid cancer and nuclear medicine, a long standing love affair. The von Hevesy Lecture to the European Association of Nuclear Medicine, Strasbourg

  • Wellman H, Zipes D, Tuli M, Minardo J, Weiland D, Liang Y (1986) I-123 MIBG demonstrating the feasibility of imaging myocardial sympathetic conduction pathway interruption in a dog model. Proceedings of the 23rd SNME/ENMS Congress, Goslar. Nuklearmedizin 34–36

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  1. Physician in Charge, Department of Nuclear Medicine, St. Bartholomew's Hospital, EC1A 7BE, West Smithfield, London, UK

    Keith E. Britton

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Invited lecture: To the European Association of Nuclear Medicine Congress, 1989, Strasbourg, France

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Britton, K.E. The development of new radiopharmaceuticals. Eur J Nucl Med 16, 373–385 (1990). https://doi.org/10.1007/BF00842796

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