Radiolabeled phosphonates for bone metastases therapy

This study is focused on the chelating process of two phosphonates with biological activity and therapeutic potential, HEDP (1-hydroxy-ethylidene-diphosphonic acid) and TTHMP (triethylene-tetramine-hexamethylene-phosphonic acid) with therapeutic radiometals 188Re (T1/2 = 17 hrs, Eβmax = 2.12 MeV, Eγ= 155 keV) and 177Lu (T1/2 = 6.7 days, Eβmax = 490 keV, Eγ = 208 keV). The ligand structure effect on the in vitro stability and on the biological affinity of the therapeutic agents was investigated. The radiochemical purity of the labeled compounds was higher than 95%, showing a good in vitro stability, up to 48 hours. The in vivo biodistribution studies, performed in rats, show a rapid and quantitative accumulation of both labeled compounds in bones and rapid elimination via the urinary tract. The maximum values of the bone uptake were ranged from 75.14% (injected dose/g organ) for 188Re-TTHMP to 94.10% for 177Lu-TTHMP. The structure of the chelates determines the kinetic of bone accumulation processes of labeled phosphonates. Its influence on the biodistribution of the radiolabeled phosphonates reveals that luthetium forms more stable chelate with polyphosphonate in respect to diphosphonate. On the other hand, the less reactive rhenium coupled with HEDP shows a better in vivo behavior than Re-TTHMP.