Nuclear Medicine and Biology
Volume 35, Issue 8 , Pages 817-824 , November 2008

What to consider in the development of new bone seekers: mechanistic and tracer-related aspects

  • Markus Mitterhauser

      Affiliations

    • Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
    • Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna, Austria
    • Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna, Austria
    • Corresponding Author InformationCorresponding author. Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria. Tel.: +43 1 40400 1557; fax: +43 1 40400 1559.
  • ,
  • Stefan Toegel

      Affiliations

    • Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria
    • Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna, Austria

Received 12 June 2008 ,Revised 4 September 2008 ,Accepted 5 September 2008.

References 

  1. Subramanian G, McAfee JG, Rosenstreich M, Coco M. Indium-113 m-labeled polyfunctional phosphonates as bone-imaging agents. J Nucl Med. 1975;16:1080–1084
  2. Billinghurst MW. Radio ion exchange in bone. In:  Billinghurst MW,  Colombetti LG editor. Studies of cellular function using radiotracers. Florida: CRC Press Inc; 1982;p. 93–114
  3. Jones AG, Davis MA, Dewarjee MK. 113mIn-labeled bone scanning agents. Radiology. 1975;117:727–730
  4. Francis MD, Fogelman I. [99mTc] Diphosphonate uptake mechanisms on bone. In:  Fogelman I editors. Bone scanning in Clinical Practice. London: Springer; 1987;p. 7–18
  5. Francis MD, Ferguson DL, Tofe AJ, Bevan JA, Michaels SE. Comparative evaluation of three diphosphonates: in vitro adsorption (C-14 labeled) and in vivo osteogenic uptake (Tc-99m complexed). J Nucl Med. 1980;21:1185–1189
  6. Chilton HM, Francis MD, Thrall JH. Radiopharmaceuticals for bone and bone marrow imaging. In:  Swanson DP,  Chilton HM,  Thrall JH editor. Pharmaceuticals in Medical Imaging. New York: Macmillan Publishing; 1990;p. 537–563
  7. Kanishi D. 99mTc-MDP accumulation mechanisms in bone. Oral Surg Oral Med O. 1993;75:239–246
  8. Nicolay OF, Heeley JD, Jeffcoat MK, Jones AG. Autoradiographic localization of technetium-99m methylene diphosphonate in growth sites of young mice. Int J Rad Appl Instrum B. 1988;15:157–163
  9. Beyer GJ, Offord R, Künzi G, Aleksandrova Y, Ravn U, Jahn S, et al. The influence of EDTMP-concentration on the biodistribution of radio-lanthanides and 225Ac in tumor-bearing mice. Nucl Med Biol. 1997;24:367–372
  10. Okamoto Y. Accumulation of technetium-99m methylene diphosphonate. Conditions affecting adsorption to hydroxyapatite. Oral Surg Oral Med O. 1995;80:115–119
  11. Elder RC, Yuan J, Helmer B, Pipes D, Deutsch K, Deutsch E. Studies of the structure and composition of rhenium-1,1-hydroxyethylidenediphosphonate (HEDP) analogues of the radiotherapeutic agent 186ReHEDP. Inorg Chem. 1997;36:3055–3063
  12. Blau M, Nagler W, Bender MA. Fluorine-18: a new isotope for bone scanning. J Nucl Med. 1962;3:332–334
  13. French RJ, McCready VR. The use of 18F for bone scanning. Br J Radiol. 1967;40:655–661
  14. Mitterhauser M, Toegel S. An in-vitro model for the comparative evaluation of bone seeking pharmaceuticals. Altex. 2008;25:51–55
  15. European Pharmacopoeia. 5th edition. Strasbourg: published by Council of Europe; 2005;
  16. Mitterhauser M, Wadsak W, Eidherr H, Krcal A, Kletter K, Dudczak R, et al. Labelling of EDTMP (Multibone®) with [111In], [99mTc] and [188Re] using different carriers for “cross complexation”. Appl Radiat Isot. 2004;60:653–658
  17. Füger B, Mitterhauser M, Wadsak W, Ofluoglu S, Traub T, Karanikas G, et al. Bone lesion detection with carrier added Tc-99m EDTMP in comparison to Tc-99m DPD. Nucl Med Com. 2004;25:361–365
  18. Mitterhauser M, Tögel S, Wadsak W, Mien LK, Eidherr H, Wiesner K, et al. Binding studies of [18F]-fluoride and polyphosphonates radiolabelled with [111In], [99mTc], [153Sm] and [188Re] on bone compartments: a new model for the pre vivo-evaluation of bone seekers?. Bone. 2004;34:835–844
  19. Mitterhauser M, Toegel S, Wadsak W, Mien LK, Eidherr H, Kletter K, et al. Binding studies of [18F]-fluoride and polyphosphonates radiolabelled with [90Y], [99mTc], [111In], [153Sm] and [188Re] on bone compartments: verification of the pre-vivo model?. Bone. 2005;37:404–412
  20. Toegel S, Mien LK, Wadsak W, Eidherr H, Viernstein H, Kluger R, et al. In-vitro evaluation of nca., ca. and cross-complexed [90Y]-EDTMP provides evidence for a novel “foreign carrier theory”. Nucl Med Biol. 2006;33:95–99
  21. Toegel S, Hoffmann O, Wadsak W, Ettlinger D, Mien LK, Wiesner K, et al. Uptake of boneseekers is solely associated with mineralisation! A study with [99mTc]-MDP, [153Sm]-EDTMP and [18F]-fluoride on osteoblasts. Eur J Nucl Med Mol Imaging. 2006;33:491–494
  22. Mitterhauser M, Toegel S, Wadsak W, Lanzenberger RR, Mien LK, Kuntner C, et al. Pre-, ex- and in-vivo evaluation of [68Ga]-EDTMP. Nucl Med Biol. 2007;34:391–397
  23. Toegel S, Wadsak W, Mien LK, Viernstein H, Kluger R, Eidherr H, et al. Preparation and pre-vivo evaluation of no-carrier-added, carrier-added and cross-complexed [68Ga]-EDTMP formulations. Eur J Pharm Biopharm. 2008;68:406–412
  24. Betts F, Blumenthal NC, Posner AS. Bone mineralization. J Crystal Growth. 1981;53:63–73
  25. Cuisinier FJG. Bone mineralization. Curr Opin Solid State Mater Sci. 1996;1:436–439
  26. Eanes ED. Crystal growth of mineral phases in skeletal tissues. Prog Cryst Growth Charact. 1980;3:3–15
  27. Robertson WG, Morgan DB, Fleisch H, Francis MD. The effects of diphosphonates on the exchangeable and non-exchangeable calcium and phosphate of hydroxyapatite. Biochim Biophys Acta. 1972;261:517–525
  28. Huigen YM, Krips HJ, Hulleman S, Gelsema WJ, De Ligny CL. The adsorption of 99mTc(Sn)-diphosphonate complexes on tri-calciumphosphate: the influence of preparation conditions, ligand-type incubation media and adsorption conditions. The reversibility of the adsorption. Int J Rad Appl Inst Part A. 1990;41:189–194
  29. Toegel S. Preclinical evaluation of bone seeking radiotracer formulations. PhD-Thesis 2007;p46.
  30. Schwartz Z, Shani J, Soskolne WA, Touma H, Amir D, Sela J. Uptake and biodistribution of technetium-99m-MD32P during rat tibial bone repair. J Nucl Med. 1993;34:104–108
  31. Sela J, Shani J, Kohavi D, Soskolne WA, Itzhak K, Boyan BD, et al. Uptake and biodistribution of 99mtechnetium methylene-[32P]diphosphonate during endosteal healing around titanium, stainless steel and hydroxyapatite implants in rat tibial bone. Biomaterials. 1995;16:1373–1380
  32. Horiuchi-Suzuki K, Konno A, Ueda M, Fukuda Y, Nishio S, Hashimoto K, et al. Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent. Eur J Nucl Med Mol Imaging. 2004;31:388–398
  33. Wang H, Gerbaudo VH, Hobbs LW, Spector M. Quantitation of osteoblasts-like cell mineralisation on tissue culture polystyrene and Ti-6Al-4V alloy disks by Tc-99m-MDP labelling and imaging in vitro. Bone. 2005;36:84–92
  34. Goeckeler WF, Edwards B, Volkert WA, Holmes RA, Simon J, Wilson D. Skeletal localization of samarium-153 chelates: potential therapeutic bone agents. J Nucl Med. 1987;28:495–504
  35. Banerjee S, Samuel G, Kothari K, Unni PR, Sarma HD, Pillai MRA. Tc-99m and Re-186 complexes of tetraphosphonate ligands and their biodistribution pattern in animal models. Nucl Med Biol. 2001;28:205–213
  36. Ando A, Ando I, Tonami N, Kinuya S, Kazuma K, Kataiwa A, et al. 177Lu-EDTMP: a potential therapeutic bone agent. Nucl Med Commun. 1998;19:587–591
  37. Ando A, Ando I, Tonami N, Kinuya S, Okamoto N, Sugimoto M, et al. Production of 105Rh-EDTMP and its bone accumulation. Appl Radiat Isot. 2000;52:211–215
  38. Hassfjell SP, Hoff P, Bruland ØS, Alstad J. 212Pb/212Bi-EDTMP synthesis and biodistribution of a novel bone seeking alpha-emitting radiopharmaceutical. J Label Compd Radiopharm. 1994;34:717–734
  39. Washiyama K, Amano R, Sasaki J, Kinuya S, Tonami N, Shiokawa Y, et al. 227Th-EDTMP: a potential therapeutic agent for bone metastasis. Nucl Med Biol. 2004;31:901–908
  40. Láznícek M, Láznícková A, Budský F, Prokop J, Kopicka K. Comparison of biological characteristics of EDTMP complexes with 99mTc, 111In and 153Sm in rats. Appl Rad Isot. 1994;45:949–953
  41. Pedraza-López M, Ferro-Flores G, Arteaga de Murphy C, Morales-Ramírez P, Piedras-Ross J, Murphy-Stack E, et al. Cytotoxic and genotoxic effect of the [166Dy]Dy/166Ho-EDTMP in vivo generator system in mice. Nucl Med Biol. 2004;31:1079–1085
  42. Srivastava SC, Meinken GE, Richards P, Som P, Oster ZH, Atkins HL, et al. The development and in-vivo behavior of tin containing radiopharmaceuticals—I. Chemistry, preparation, and biodistribution in small animals. Int J Nucl Med Biol. 1985;12:167–174
  43. Lin WY, Hsieh JF, Lin CP, Hsieh BT, Ting G, Wang SJ, et al. Effect of reaction conditions on preparations of rhenium-188 hydroxyethylidene diphosphonate complexes. Nucl Med Biol. 1999;26:455–459
  44. Palmedo H, Guhlke S, Bender H, Sartor J, Schoeneich G, Risse J, et al. Dose escalation study with rhenium-188 hydroxyethylidene biphosphonate in prostate cancer patients with osseous metastases. Eur J Nucl Med. 2000;27:123–130
  45. Hsieh BT, Hsieh JF, Tsai SC, Lin WY, Wang SJ, Ting G. Comparison of various rhenium-188-labeled diphosphonates for the treatment of bone metastases. Nucl Med Biol. 1999;26:973–976
  46. Hashimoto K, Matsuoka H, Izumo M. Adsorption of 188Re complexes with aminomethylenephosphonate on hydroxyapatite. J Nucl Radiochem Sci. 2001;2:5–9
  47. Oh SJ, Won KS, Moon DH, Cheon JH, Ha HJ, Jeong JM, et al. Preparation and biological evaluation of 188Re-ethylenediamine-N,N,N′,N′-tetrakis(methylene phosphonic acid) as a potential agent for bone pain palliation. Nucl Med Comm. 2002;23:75–81
  48. Hosain P. Technetium-99m labelled pyrophosphate: a simple and reproducible bone scanning agent. Br J Radiol. 1973;46:724–728
  49. Fletcher JW, Solaric-George E, Henry RE, Donati RM. Evaluation of 99mTc-pyrophosphate as a bone imaging agent. Radiology. 1973;109:467–468
  50. Silberstein EB, Saenger EL, Tofe AJ, Alexander GW, Park HM. Imaging of bone metastases with 99mTc-Sn-EHDP (diphosphonate), 18F, and skeletal radiography. A comparison of sensitivity. Radiology. 1973;107:551–555
  51. Citrin DL, Bessent RG, McGinley E, Gordon D. Dynamic studies with 99mTc-HEDP in normal subjects and in patients with bone tumors. J Nucl Med. 1975;16:886–890
  52. Dewanjee MK, Hnatowich DJ, Beh R. New 68Ga-labeled skeletal-imaging agents for positron scintigraphy. J Nucl Med. 1976;17:1003–1007
  53. Dormehl IC, Louw WK, Schneeweiss FH, Milner R, Schmitt G, Carl U, et al. Uptake of ethylenediamine tetramethylene phosphonic acid in normal bone after multiple applications. A non-human primate study. Arzneimittelforschung. 1998;48:408–414
  54. Claessens RA, Kolar ZI. Affinity of Tin(II) and Tin(II) diphosphonates for hydroxyapatite: an experimental and model study. Langmuir. 2000;16:1360–1367
  55. Hashimoto K. Synthesis of a 188Re-HEDP complex using carrier-free 188Re, and a study of its stability. Appl Radiat Isot. 1998;49:351–356
  56. de Groot GJ, Das HA, de Ligny CL. The effect of the reduction method on the composition of 99mTc-EHDP complexes. Int J Rad Appl Instrum [A]. 1987;38:611–614
  57. Ghanem N, Kelly T, Altehoefer C, Winterer J, Schafer O, Bley TA, et al. Whole-body MRI in comparison to skeletal scintigraphy for detection of skeletal metastases in patients with solid tumors. Radiologe. 2004;44:864–873
  58. Mentzel HJ, Kentouche K, Sauner D, Fleischmann C, Vogt S, Gottschild D, et al. Comparison of whole-body STIR-MRI and 99mTc-methylene-diphosphonate scintigraphy in children with suspected multifocal bone lesions. Eur Radiol. 2004;14:2297–2302
  59. Lauenstein TC, Goehde SC, Herborn CU, Goyen M, Oberhoff C, Debatin JF, et al. Whole-body MR imaging: evaluation of patients for metastases. Radiology. 2004;233:139–148
  60. Eustace S, Tello R, DeCarvalho V, Carey J, Wroblicka JT, Melhem ER, et al. A comparison of whole-body turboSTIR MR imaging and planar 99mTc-methylene diphosphonate scintigraphy in the examination of patients with suspected skeletal metastases. AJR Am J Roentgenol. 1997;169:1655–1661
  61. Daldrup-Link HE, Franzius C, Link TM, Laukamp D, Sciuk J, Jurgens H, et al. Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET. AJR Am J Roentgenol. 2001;177:229–236
  62. Gaa J, Rummeny EJ, Seemann MD. Whole-body imaging with PET/MRI. Eur J Med Res. 2004;30:309–312
  63. Engelhard K, Hollenbach HP, Wohlfart K, von Imhoff E, Fellner FA. Comparison of whole-body MRI with automatic moving table technique and bone scintigraphy for screening for bone metastases in patients with breast cancer. Eur Radiol. 2004;14:99–105
  64. Lauenstein TC, Freudenberg LS, Goehde SC, Ruehm SG, Goyen M, Bosk S, et al. Whole-body MRI using a rolling table platform for the detection of bone metastases. Eur Radiol. 2002;12:2091–2099
  65. Plato. Apology of Socrates. estimated 399-395 B.C.;1:21d.

PII: S0969-8051(08)00182-0

doi: 10.1016/j.nucmedbio.2008.09.003

Nuclear Medicine and Biology
Volume 35, Issue 8 , Pages 817-824 , November 2008