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


CONCLUSIONS
166Ho-DOTMP has physical and pharmacokinetic characteristics compatible with high-dose myeloablative treatment of multiple myeloma.
D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use; D016465:Bone Marrow Purging; D005260:Female; D006695:Holmium / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000532:radiotherapy*; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011868:Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011874:Radiometry; D011879:Radiotherapy Dosage; D014018:Tissue Distribution
D018906:Antineoplastic Agents, Alkylating; D009943:Organophosphorus Compounds; D011868:Radioisotopes; C082084:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonic acid); D008558:Melphalan; D006695:Holmium