(170)Tm-EDTMP: a potential cost-effective alternative to (89)SrCl(2) for bone pain palliation.
BACKGROUND
Metastron ((89)SrCl(2)) is a radiopharmaceutical currently used for bone pain palliation in several countries since the long half-life of (89)Sr (50.5 days) favors wider distribution than other radioisotopes approved for this application, which have shorter half-lives. Strontium-89 is not ideal for bone pain palliation due to its high energy beta(-) particle emission [E(beta(max))=1.49 MeV] and is also difficult to produce in large quantities. A (170)Tm [T(1/2)=128.4 days, E(beta(max))=968 keV, E(gamma)=84 keV (3.26%)]-based radiopharmaceutical for bone pain palliation could offer significant advantages over that of (89)Sr. The present study constitutes the first report of the preparation of a (170)Tm-based agent, (170)Tm-ethylenediaminetetramethylene phosphonic acid (EDTMP), and its preliminary biological evaluation in animal models.


METHODS
(170)Tm was produced by thermal neutron bombardment on natural Tm(2)O(3) target for a period of 60 days at a flux of 6x10(13) neutrons/cm(2).s. (170)Tm-EDTMP complex was prepared at room temperature. Biodistribution and scintigraphic imaging studies with (170)Tm-EDTMP complex were performed in normal Wistar rats. Preliminary dosimetric estimation was made using the data to adjudge the suitability of (170)Tm-EDTMP for bone pain palliation.


RESULTS
(170)Tm was produced with a specific activity of 6.36 GBq/mg and radionuclidic purity of 100%. The (170)Tm-EDTMP was prepared with high radiochemical purity (>99%) and the complex exhibited satisfactory in vitro stability. Biodistribution and imaging studies showed good skeletal accumulation (50-55% of the injected activity) with insignificant uptake in any other vital organ/tissue. Activity was observed to be retained in skeleton until 60 days post-injection demonstrating that (170)Tm-EDTMP exhibits good bone-seeking properties with long retention. It is predicted that a dose of approximately 0.5 microGy/MBq is accrued to red bone marrow and 4.3 Gy/MBq is delivered to the skeleton.


CONCLUSIONS
(170)Tm-EDTMP shows promising biodistribution features, encouraging dosimetric values and warrants further investigation in order to develop it as a bone pain palliative radiopharmaceutical. Despite the relatively long half-life (128.4 days) of (170)Tm, (170)Tm-EDTMP could be explored as a cost-effective alternative to (89)SrCl(2).
Das
Tapas
T
Bhabha Atomic Research Centre, Mumbai, India.
Chakraborty
Sudipta
S
Sarma
Haladhar D
HD
Tandon
Pankaj
P
Banerjee
Sharmila
S
Venkatesh
Meera
M
Pillai
Maroor R A
MR
D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology* / Q000528:radiation effects; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D063065:Organophosphonates / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010146:Pain / Q000532:radiotherapy*; D010166:Palliative Care / Q000191:economics* / Q000379:methods*; D011868:Radioisotopes; D011874:Radiometry; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013324:Strontium / Q000627:therapeutic use*; D013932:Thulium / Q000737:chemistry*; D014018:Tissue Distribution
C543419:170Tm-ethylenediamine-tetramethylenephosphonic acid; D009942:Organometallic Compounds; D063065:Organophosphonates; D011868:Radioisotopes; D013932:Thulium; C025700:strontium chloride; D013324:Strontium