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High-dose 166Ho-DOTMP in myeloablative treatment of multiple myeloma: pharmacokinetics, biodistribution, and absorbed dose estimation.

AbstractUNLABELLED:
Thirty-two patients with multiple myeloma were treated with high doses of 166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid (DOTMP) and were a subset of patients enrolled in a multicenter phase I/II dose escalation myeloablative trial. 166Ho with beta-emission (half-life, 26.8 h; beta-particle energies, 1.85 MeV [51%] and 1.77 MeV [48%]; gamma-photons, 80.6 keV [6.6%] and 1.38 MeV [0.9%]) was complexed to DOTMP, a macrocyclic tetraphosphonate. Pharmacokinetics, dosimetry, and biodistribution were studied.
METHODS:
Patients were treated at escalating dose levels of 20, 30, and 40 Gy to the bone marrow in combination with high-dose melphalan, with or without total-body irradiation, to evaluate toxicity and efficacy. After infusion with 1,110 MBq (30 mCi) of 166Ho-DOTMP for evaluation of biodistribution and dosimetry calculation, patients received the calculated amount of radioactivity for therapy in a single administration based on estimated dose calculations.
RESULTS:
Thirty-two patients participated in the study and were then treated. The average amount of administered radioactivity was 74.3 GBq (2,007 mCi) (range, 21.5-147.5 GBq [581-3,987 mCi]) of 166Ho-DOTMP.
CONCLUSION:
166Ho-DOTMP has physical and pharmacokinetic characteristics compatible with high-dose myeloablative treatment of multiple myeloma.
AuthorsJoseph G Rajendran, Janet F Eary, William Bensinger, Larry D Durack, Cheryl Vernon, Alan Fritzberg
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 43 Issue 10 Pg. 1383-90 (Oct 2002) ISSN: 0161-5505 [Print] United States
PMID12368378 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
Chemical References
  • Antineoplastic Agents, Alkylating
  • Organophosphorus Compounds
  • Radioisotopes
  • 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonic acid)
  • Melphalan
  • Holmium
Topics
  • Antineoplastic Agents, Alkylating (administration & dosage, therapeutic use)
  • Bone Marrow Purging
  • Female
  • Holmium (administration & dosage, therapeutic use)
  • Humans
  • Male
  • Melphalan (administration & dosage, therapeutic use)
  • Middle Aged
  • Multiple Myeloma (radiotherapy)
  • Organophosphorus Compounds (administration & dosage, pharmacokinetics, therapeutic use)
  • Radioisotopes (administration & dosage, pharmacokinetics, therapeutic use)
  • Radiometry
  • Radiotherapy Dosage
  • Tissue Distribution

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