Development of therapeutic radiopharmaceuticals based on 177Lu for radionuclide therapy

Designing of radiotherapeutics using indigenously produced 177Lu as a potential radioisotope is the focus of the Coordinated Research Project. Amongst the various agents that are envisaged, the designing of bone-pain palliatives will be the major objective of the work. The sourcing of 177Luas a radionuclide that could be readily produced with specific activities suitable for non-saturable targets (e.g. bone-pain palliation) and at least also suitable for low-capacity targets such as peptide receptors has been demonstrated. Irradiations were carried out at different available flux positions for different durations (7-21 d) for optimizing the irradiation conditions toward achieving maximum specific gravity using natural as well as enriched targets. While ∼4 TBq.g-1 (108 Ci.g-1) of 177Lu was obtainable using natural Lu target after 7 d irradiation at 3x1013 n/cm2.s thermal neutron flux, it was ∼170 TBq.g-1 (4600 Ci.g-1) of 177Lu when 64.3% enriched 176Lu target was used. In both cases, radionuclidic purity was ∼100%, only insignificant quantity of 177mLu [T1/2 160.5 d, Eβ(max) = 200 keV] could be detected as the radionuclidic impurity. Using the existing irradiation facilities, 177Lu could be produced with a maximum specific activity of ∼23185 Ci.g-1 (850 TBq.g-1) using enriched 176Lu (64.3%) target at a thermal neutron flux of 1x1014 n/cm2.s for 21 d. Ethylenediaminetetramethylene phosphonic acid was synthesised in-house and spectrochemically characterised. The radiolabelling parameters were optimised and an optimum protocol was arrived at. In vivo distribution studies in rats have been carried out to ascertain the skeletal uptake and other pharmacokinetic parameters. Imaging studies in rabbits and dogs bearing natural osteosarcoma have been carried out with the 177Lu-EDTMP complex. (author)