title: On the preparation of a therapeutic dose of 177Lu-labeled DOTA-TATE using indigenously produced 177Lu in medium flux reactor.
abstract: 177Lu could be produced with a specific activity of approximately 23,000 mCi/mg (850GBq/mg) by neutron activation using enriched 176Lu (64.3%) target when irradiation was carried out at a thermal neutron flux of 1 x 10(14) n/cm(2)/s for 21 d. 177Lu-DOTA-TATE could be prepared in high radiochemical yield (approximately 99%) and adequate stability using the 177Lu produced indigenously. The average level of radionuclidic impurity burden in 177Lu due to 177mLu was found to be 250 nCi of 177mLu/1 mCi of 177Lu (9.25 kBq/37 MBq) at the end of bombardment, which corresponds to 0.025% of the total activity produced. The maximum specific activity achievable via careful optimization of the irradiation parameters was found to be adequate for the preparation of a therapeutic dose of the radiopharmaceutical. The in-house preparation of this agent using 25 microg (17.41 nmole) of DOTA-TATE and indigenously produced 177Lu (0.8 microg, 4.52 nmole), corresponding to peptide/Lu ratio of 3.85 yielded 98.7% complexation. Allowing possibility of decay due to transportation to users, it has been possible to demonstrate that at our end, a single patient dose of 150-200 mCi (5.55-7.40 GBq) can be prepared by using 250-333 microg of DOTA-TATE conjugate. This amount compares well with 177Lu-DOTA-TATE prepared for a typical peptide receptor radionuclide therapy (PRRT) procedure which makes use of 100 microg of the DOTA-TATE conjugate, which incorporates 50 mCi (1.85 GBq) of 177Lu activity, thereby implying that in order to achieve a single patient dose of 150-200 mCi (5.55-7.40 GBq), 300-400 microg of the conjugate needs to be used.
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai-400085, India.
authors.forename: Tapas
authors.initials: T
authors.lastname: Das
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesh
mesh_terms: D004355:Drug Stability; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000627:therapeutic use; D007553:Isotope Labeling / Q000379:methods*; D008187:Lutetium; D015282:Octreotide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000138:chemical synthesis
chemical_list: C476041:DOTA-Tyr(1)-octreotate; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; D015282:Octreotide