Abstract
153Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153Sm-EDTMP in 15 of 19 patients (79%) who could be evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow ≥270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 1.0% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153Sm-EDTMP-induced myclotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients.
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Blake GM, Gray JM, Zivanovic MA, McEwan AJ, Fleming JA, Ackery DM (1987a) Strontium-89 radionuclide therapy: a dosimetric study using impulse response function analysis. Br J Radiol 60:685–692
Blake GM, Zivanovic MA, McEwan AJ, Batty VB, Ackery DM (1987b) 89 Sr radionuclide therapy: Dosimetry and haematological toxicity in two patients with metastasising prostatic carcinoma. Eur J Nucl Med 13:41–46
Buchali K, Correns H-J, Schuerer M, Schnorr D, Lips H, Sydow K (1988) Results of a double blind study of 89-Strontium therapy of skeletal metastases of prostatic carcinoma. Eur J Nucl Med 14:349–351
Correns H-J, Mebel M, Buchali K, Schnor D, Seidel C, Mitterlechner E (1979) 89-Strontium therapy of bone metastases of carcinoma of the prostatic gland. Eur J Nucl Med 4:33–35
Corwin LA, Lattimer JC, Goeckeler WF, Stapleton J, Edwards BE, Stringham L, Simon J, Ketring AR, Volkert WA, Holmes RA (1986) Sm-153 EDTMP treatment for spontaneous canine bone tumours. J Nucl Med 27:986 (abstr)
Coursey BM, Hoppes DD, Schima FJ, Unterweger MP (1987) The standardization of Samarium-153. App Radiat Isot 38:31–34
Eisenhut M (1984) Iodine-131 labelled diphosphonates for the palliative treatment of bone metastases: 1. organ distribution and kinetics of I-131 BDP3 in rats. J Nucl Med 25:1356–1361
Eisenhut M, Berberich R, Kimmig B, Oberhausen E (1986) Iodine-131-labelled diphosphonates for palliative treatment of bone metastases: II. Preliminary clinical results with iodine-131 BDP3. J Nucl Med 27:1255–1261
Firusian N, Mellin P, Schmidt CG (1976) Results of 89 Strontium therapy in patients with carcinoma of the prostate and incurable pain from bone metastases: A preliminary report. J Urology 116:764–768
Ford HT, Yarnold JR (1983) Radiation therapy — pain relief and recalcification. Bone metastasis: monitoring and treatment. Raven Press, New York
Friedell HL, Storaasli JP (1950) The use of radioactive phosphorous in the treatment of carcinoma of the breast with widespread metastasis to bone. Am J Roentgenol 64:559–575
Garrow JS (1981) Treat obesity seriously. Churchill Livingstone Edinburgh
Goeckeler WF, Edwards B, Volkert WA, Holmes RA, Simon J, Wilson D (1987) Skeletal localization of Samarium-153 chelates: Potential therapeutic bone agents. J Nucl Med 28:495–504
Harbert JC (1987) Radionuclide therapy of bone pain. In: Harbert JC (ed) Nuclear medicine therapy. Thieme Medical, New York pp 207–219
Hendrikson FR, Sheinkop MB (1975) Management of osseous metastases. Semin Oncol 2:399–404
Holmes RA, Farhangi M (1988) Dose tolerance of Sm-153 EDTMP in metastatic bone cancer. J Nucl Med 29:775 (abstr)
ICRP Publication 26 (1977) Recommendations of the ICRP. Pergamon Press, Oxford
ICRP Publication 30 (1979) Limits for intakes of radionuclides by workers. Pergamon Press, Oxford
ICRP Publication 53 (1988) Radiation dose to patients from radiopharmaceuticals. Annals of ICRP Pergamon Press, Oxford
Kaplan E, (1978) Historical development of 32P in bone therapy. In: Spencer RP (ed) Therapy in Nuclear Medicine. Grune and Stratton, New York pp. 237–249
Kutzer J, Dahnert W, Schreyer T (1981) Yttrium-90 zur Schmerztherapie von Knochenmetastasen. Nucl Med 20:229–235
Logan KW, Volkert WA, Holmes RA (1987) Radiation dose calculations in persons receiving injection of Samarium-153 EDTMP. J Nucl Med 28:505–509
McEwan AJB, Porter AT, Venner PM, Amyotte GA (1988) Strontrium-89 to palliate patients with metastatic prostate cancer following wide field radiotherapy. J Nucl Med 29:775 (abstr)
Matthieu L, Chevalier P, Galy G, Berger M (1979) Preparation of 186-Rhenium labelled HEDP and its possible use in the treatment of osseous neoplasms. Int J Appl Radiat Isot 30:725–727
Maxon HR, Deutsch EA, Thomas SR, Libson K, Lukes SJ, Williams CC, Alo S (1988a) Re-186 (Sn) HEDP for treatment of multiple metastatic foci in bone: Human biodistribution and dosimetric studies. Radiol 166:501–507
Maxon HR, Deutsch EA, Thomas SR, Moulton JS, Schroder IE, Libson KF, Soldano M, Williams CC, Cummings DD (1988b) Initial experience with 186-Re (Sn)-HEDP in the treatment of painful skeletal metastases. J Nucl Med 29:776 (abstr)
Moedritzer K, Irani RR (1966) The direct synthesis of α-aminomethyl phosphonic acids. Mannich-type reactions with orthophosphorous acid. J Organic Chem 31:1603–1607
Pecher C (1942) Biological investigations with radioactive calcium and strontium: Preliminary report on the use of radioactive strontium in treatment of metastatic bone cancer. Univ Calf Publ Pharmacol 11:117–139
Rappeport JM, Bunn FH (1987) Bone marrow failure. In: Harrison's Principles of Internal Medicine, 11th Ed. McGraw-Hill, New York, pp 1536
Robinson RG (1986) Radionuclides for the alleviation of bone pain in advanced malignancy. Clin Oncol 5:39–49
Robinson RG, Spicer JA, Preston DF, Wegst AV, Martin NL (1987) Treatment of metastatic bone pain with Strontium-89. J Nucl Med 28:553
Rossleigh MA, Lovegrove FTA, Reynolds PM, Byrne MJ (1982) Serial bone scans in the assessment of response to therapy in advanced breast carcinoma. Clin Nucl Med 7:397–402
Silberstein EB, Williams C (1985): Strontium-89 therapy for the pain of osseous metastases. J Nucl Med 26:345–348
Silberstein EB, Williams CC (1988) Marrow toxicity of Strontium-89 in the therapy of osseous metastases. J Nucl Med 29:776 (abstr)
Snyder WS, Ford MR, Warner GG, Watson SB (1975) “S”, absorbed dose per unit cumulated activity for selected radionuclides and organs. MIRD pamphlet No. 11. Society of Nuclear Medicine New York
Spencer RP (1987) Short lived radionuclides in therapy. Nucl Med Biol 14:537–538
Turner JH, Hoffman RF, Martindale AA, Hetherington EL, Sorby P, Claringbold PG (1988) Samarium-153 EDTMP therapy dosimetry and SPECT in cancer patients with disseminated skeletal metastasis. J Nucl Med 29:762–763 (abstr)
Turner JH, Martindale AA, de Witt CG, Webb J, Sorby P, Boyd RE (1987) Samarium-153 chelate localization in malignant melanoma. Eur J Nucl Med 13:432–438
Van Nostrand D, Silberstein EB (1985) Therapeutic uses of 32P. Nucl Med Annual 285–342. Raven Press, New York
Wallenstein SL (1984) Measurement of pain and analgesia in cancer patients. Cancer 53:2260–2266
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Turner, J.H., Martindale, A.A., Sorby, P. et al. Samarium — 153 EDTMP therapy of disseminated skeletal metastasis. Eur J Nucl Med 15, 784–795 (1989). https://doi.org/10.1007/BF00255498
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DOI: https://doi.org/10.1007/BF00255498