Nuclear Medicine and Biology
Volume 36, Issue 1 , Pages 39-45 , January 2009

Synthesis and biodistribution of lipophilic and monocationic gallium radiopharmaceuticals derived from N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine: potential agents for PET myocardial imaging with 68Ga

  • Yui-May Hsiao

      Affiliations

    • Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
  • ,
  • Carla J. Mathias

      Affiliations

    • Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
  • ,
  • Shiaw-Pyng Wey

      Affiliations

    • Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
  • ,
  • Phillip E. Fanwick

      Affiliations

    • Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA
  • ,
  • Mark A. Green

      Affiliations

    • Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 765 494 1445; fax: +1 765 496 3367.

Received 9 May 2008 ,Revised 18 September 2008 ,Accepted 21 October 2008.

References 

  1. Green MA, Welch MJ. Gallium radiopharmaceutical chemistry. Nucl Med Biol. 1989;16:435–448
  2. Green MA. The potential for generator-based PET perfusion tracers. J Nucl Med. 1990;31:1641–1645
  3. Green MA. Gallium and copper radiopharmaceutical chemistry. In:  Emram AM editors. New trends in radiopharmaceutical synthesis, quality assurance and regulatory control. New York: Plenum; 1991;p. 119–127
  4. Weiner RE, Thakur ML. Chemistry of gallium and indium radiopharmaceuticals. In:  Welch MJ,  Redvanly C editor. Handbook of radiopharmaceuticals. New York: Wiley; 2003;p. 363–399
  5. Al-Nahhas A, Win Z, Szyszko T, Singh A, Khan S, Rubello D. What can gallium-68 PET add to receptor and molecular imaging?. Eur J Nucl Med Mol Imag. 2007;34:1897–1901
  6. Breeman WAP, Verbruggen AM. The 68Ge/68Ga generator has high potential, but when can we use68Ga-labelled tracers in clinical routine?. Eur J Nucl Med Mol Imag. 2007;34:978–981
  7. In:  Lederer CM,  Shirley VS editor. Table of isotopes. 7th ed.. New York: Wiley; 1978;
  8. Green MA, Welch MJ, Mathias CJ, Fox KAA, Knabb RM, Huffman JC. Gallium-68 1,1,1-tris(5-methoxysalicylaldiminomethyl)ethane: a potential tracer for evaluation of regional myocardial blood flow. J Nucl Med. 1985;26:170–180
  9. Green MA. Synthesis and biodistribution of a series of lipophilic gallium-67 tris(salicylaldimine) complexes. J Labelled Compds Radiopharm. 1986;23:1227–1229
  10. Green MA, Mathias CJ, Neumann WL, Fanwick PE, Janik M, Deutsch EA. Potential gallium-68 tracers for imaging the heart with PET: evaluation of four gallium complexes with functionalized tripodal tris(salicylaldimine) ligands. J Nucl Med. 1993;34:228–233
  11. Tsang BW, Mathias CJ, Green MA. A gallium-68 radiopharmaceutical that is retained in myocardium: 68Ga[(4,6-(MeO)2sal)2BAPEN]+. J Nucl Med. 1993;34:1127–1131
  12. Tsang BW, Mathias CJ, Fanwick PE, Green MA. Structure–distribution relationships for metal-labeled myocardial imaging agents: comparison of a series of cationic gallium(III) complexes with hexadentate bis(salicylaldimine) ligands. J Med Chem. 1994;37:4400–4406
  13. Tsang BW, Mathias CJ, Green MA. Structure–activity relationships for cationic Ga(III) bis(salicylaldimine) radiopharmaceuticals that are retained in myocardium. J Nucl Med. 1993;34:79P
  14. Kung HF, Liu BL, Mankoff D, Kung MP, Billings JJ, Francesconi L, et al. A new myocardial imaging agent: synthesis, characterization, and biodistribution of gallium-68-BAT-TECH. J Nucl Med. 1990;31:1635–1640
  15. Plössl K, Chandra R, Qu W, Lieberman BP, Kung MP, Zhou R, et al. A novel gallium bisaminothiolate complex as a myocardial perfusion imaging agent. Nucl Med Biol. 2008;35:83–90
  16. Moerlein SM, Daugherty A, Sobel BE, Welch MJ. Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein. J Nucl Med. 1991;32:300–307
  17. Klivényi G, Schuhmacher J, Patzelt E, Hauser H, Matys R, Moock M, et al. Gallium-68 chelate imaging of human colon carcinoma xenografts pretargeted with bispecific anti-CD44V6/anti-gallium chelate antibodies. J Nucl Med. 1998;39:1769–1776
  18. Hoffend J, Mier W, Schuhmacher J, Schmidt K, Dimitrakopoulou-Strauss A, Strauss L, et al. Gallium-68-DOTA-albumin as a PET blood-pool marker: experimental evaluation in vivo. Nucl Med Biol. 2005;32:287–292
  19. Smith-Jones PM, Stolz B, Bruns C, Albert R, Reist HW, Fridrich R, et al. Gallium-67/Gallium-68-[DFO]-octreotide — a potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors: synthesis and radiolabeling in vitro and preliminary in vivo studies. J Nucl Med. 1994;35:317–325
  20. Griffiths GL, Chang CH, McBride WJ, Rossi EA, Sheerin A, Tejada GR, et al. Reagents and methods for PET using bispecific antibody pretargeting and 68Ga-radiolabeled bivalent hapten-peptide-chelate conjugates. J Nucl Med. 2004;45:30–39
  21. Jeong JM, Hong MK, Chang YS, Lee YS, Kim YJ, Cheon GJ, et al. Preparation of a promising angiogenesis PET imaging agent: 68Ga-labeled c(RGDyK)-isothiocyanatobenzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid and feasibility studies in mice. J Nucl Med. 2008;49:830–836
  22. Hawkins RA, Phelps ME, Huang SC, Wapenski SA, Grimm PD, Parker RG, et al. A kinetic evaluation of blood–brain barrier permeability in human brain tumors with 68Ga-EDTA and PET. J Cereb Blood Flow Metab. 1984;4:507–515
  23. Calandrino FS, Anderson DJ, Mintun MA, Schuster DP. Pulmonary vascular permeability during the adult respiratory distress syndrome: a positron emission tomography study. Am Rev Respir Dis. 1988;138:421–428
  24. Mintun MA, Dennis DR, Welch MJ, Mathias CJ, Schuster DP. Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin. J Nucl Med. 1987;28:1704–1716
  25. Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J, et al. PET imaging of somatostatin receptors using [68GA]DOTA-d-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med. 2001;42:1053–1056
  26. Henze M, Schuhmacher J, Dimitrakopoulou-Strauss A, Strauss LG, Mäcke HR, Eisenhut M, et al. Exceptional increase in somatostatin receptor expression in pancreatic neuroendocrine tumour, visualised with (68)Ga-DOTATOC PET. Eur J Nucl Med Mol Imag. 2004;31:466
  27. Dimitrakopoulou-Strauss A, Hohenberger P, Haberkorn U, Mäcke HR, Eisenhut M, Strauss LG. 68Ga-labeled bombesin studies in patients with gastrointestinal stromal tumors: comparison with 18F-FDG. J Nucl Med. 2007;48:1245–1250
  28. Sharma VJ, Beatty A, Wey SP, Dahlheimer J, Pica CM, Crankshaw CL, et al. Novel gallium(III) complexes transported by MDR1 P-glycoprotein: potential PET imaging agents for probing P-glycoprotein-mediated transport activity in vivo. Chem Biol. 2000;7:335–343
  29. Sharma V, Crankshaw CL, Piwnica-Worms D. Effects of multidrug resistance (MDR1) P-glycoprotein expression levels and coordination metal on the cytotoxic potency of multidentate (N4O2) (ethylenediamine)bis[propyl(R-benzylimino)]metal(III) cations. J Med Chem. 1996;39:3483–3490
  30. Sharma V, Prior JL, Belinsky MG, Kruh GD, Piwnica-Worms D. Characterization of a 67Ga/68Ga radiopharmaceutical for SPECT and PET of MDR1 P-glycoprotein transport activity in vivo: validation in multidrug-resistant tumors and at the blood–brain barrier. J Nucl Med. 2005;46:354–364
  31. Donaldson HH. In: The rat. Philadelphia: Wistar Institute; 1915;p. 75
  32. Iwasa J, Fujita T, Hansch C. Substituent constants for aliphatic functions obtained from partition coefficients. J Med Chem. 1965;8:150–153
  33. Leo A, Hansch C, Elkins D. Partition coefficients and their uses. Chem Rev. 1971;71:525–616
  34. Schwaiger M. Myocardial perfusion imaging with PET. J Nucl Med. 1994;35:693–698
  35. Merhige ME, Breen WJ, Shelton V, Houston T, D'Arcy BJ, Perna AF. Impact of myocardial perfusion imaging with PET and 82Rb on downstream invasive procedure utilization, costs, and outcomes in coronary disease management. J Nucl Med. 2007;48:1069–1076
  36. Deutsch E, Ketring AR, Libson K, Vanderheyden J, Hirth WW. The Noah's ark experiment: species dependent biodistributions of cationic 99mTc complexes. Nucl Med Biol. 1989;16:191–232

PII: S0969-8051(08)00232-1

doi: 10.1016/j.nucmedbio.2008.10.010

Nuclear Medicine and Biology
Volume 36, Issue 1 , Pages 39-45 , January 2009