Pharmacokinetics, dosimetry and toxicity of holmium-166-DOTMP for bone marrow ablation in multiple myeloma.
In this Phase I clinical trial, six multiple myeloma patients who had not responded to conventional therapy and were scheduled for bone marrow transplantation received a bone-seeking radiopharmaceutical for bone marrow ablation. The pharmacokinetics, dosimetry, and toxicity of this radiopharmaceutical were studied.


METHODS
Patients received from 519 mCi to 2.1 Ci (19.2 GBq to 77.7 GBq) of holmium-166 (166Ho) complexed with a bone-seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid). The reproducibility of pharmacokinetics from multiple injections of 166Ho-DOTMP administered to these myeloma patients was demonstrated from blood (r2 = 0.926) and whole-body retention (r2 = 0.983), which allowed therapeutic parameters to be determined from a diagnostic study.


RESULTS
Over 50% of the 166Ho-DOTMP injected dose was excreted within 2-3 hr postinjection, increasing to 75%-85% over a 24-hr period. Rapid blood clearance minimized radiation dose to nontarget tissue: less than 10% of the injected activity was retained in the blood pool at 1 hr postinjection, and less than 2% remained after 5 hr. The total radiation absorbed dose delivered to the bone marrow for the six patients ranged from 7.9 Gy to 41.4 Gy.


CONCLUSIONS
All patients demonstrated severe bone marrow toxicity with a white blood cell (WBC) count < 1,000 cells/microliters, two patients exhibited marrow ablation (WBC count < 100 cells/microliters), and no other toxicity > or = grade 2 was observed in any of the patients.
Bayouth
J E
JE
Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston, USA.
Macey
D J
DJ
Kasi
L P
LP
Garlich
J R
JR
McMillan
K
K
Dimopoulos
M A
MA
Champlin
R E
RE
D001853:Bone Marrow / Q000473:pathology / Q000528:radiation effects; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D006801:Humans; D007958:Leukocyte Count; D009101:Multiple Myeloma / Q000097:blood / Q000628:therapy*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011829:Radiation Dosage
D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C093387:holmium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetrakis(methylenephosphonic acid)