Lu-177 DOTATATE Research Articles

Results of Individual Patient Dosimetry in Peptide Receptor Radionuclide Therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC

One of the few treatment options for inoperable neuroendocrine tumors (NET) is peptide receptor radiotherapy with somatostatin analogs. In this study, we compared the dosimetric parameter uptake, half-life (kinetics), and mean absorbed organ and tumor doses of (177)Lu DOTA-NOC and (177)Lu DOTA-TATE. Ninety-five (95) post-therapeutic dosimetric assessments using (177)Lu DOTA-TATE and 8 using (177)Lu DOTA-NOC in 69 patients with neuroendocrine tumors with high somatostatin receptor expression (verified by Ga-68 DOTA-NOC positron emission tomography/computed tomography) were analyzed. Dosimetric calculations were performed according to the Medical Internal Radiation Dose scheme. (177)Lu DOTA-NOC showed a significantly (p < or = 0.05; sign test) higher uptake for whole-body and normal tissue, as compared to (177)Lu DOTA-TATE, leading to a significant higher whole-body dose of 0.07 mGy/ MBq for DOTA-NOC, as compared to 0.05 mGy/MBq for DOTA-TATE. Renal and spleen uptake and radiation doses were not significantly higher for DOTA-NOC. The uptake in tumor lesions and the mean absorbed tumor dose were higher for DOTA-TATE. The red marrow dose was approximately 0.2 Gy. Our first results demonstrated that the higher in vitro affinity of DOTA-NOC leads to a higher uptake in normal tissues and, therefore, to an increase in the whole-body dose. The high interpatient variability of these results makes an individual patient dosimetry obligatory.

On the preparation of a therapeutic dose of 177Lu-labeled DOTA–TATE using indigenously produced 177Lu in medium flux reactor

177Lu could be produced with a specific activity of ∼23,000 mCi/mg (850 GBq/mg) by neutron activation using enriched 176Lu (64.3%) target when irradiation was carried out at a thermal neutron flux of 1×10 14 n/cm 2/s for 21 d. 177Lu–DOTA–TATE could be prepared in high radiochemical yield (∼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 μg (17.41 nmole) of DOTA–TATE and indigenously produced 177Lu (0.8 μg, 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 μg 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 μg 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 μg of the conjugate needs to be used.