Semiautomated labelling and fractionation of yttrium-90 and lutetium-177 somatostatin analogues using disposable syringes and vials (original) (raw)
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Journal of labelled compounds & radiopharmaceuticals, 2015
The clinical applications of radiolabeled somatostatin analogue (177) Lu-DOTA-Tyr(3) -Thr(8) -Octreotide ((177) Lu-DOTATATE) constitute a promising treatment option for patients with disseminated and inoperable neuroendocrine (NET) tumors. Formulation of (177) Lu-DOTATATE in hospital radiopharmacy under aseptic conditions in a safe and reliable manner is a major constraint for its extensive use. The present work was intended to develop a kit for the safe preparation of the therapeutic radiopharmaceutical, viz. (177) Lu-DOTATATE of high quality that can be easily adapted at conventional hospital radiopharmacies. Single vial kits of DOTATATE were formulated and evaluated for suitability for radiolabeling as well as stability on its storage. Patient dose of (177) Lu-DOTATATE (7.4 GBq) could be successfully prepared using semi-automated in-house setup that assures safe handling and high yields of product of pharmaceutical purity suitable for clinical use. Fast clearance of activity via ...
Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System
Asia Oceania Journal of Nuclear Medicine and Biology, 2015
Objective(s): Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 (90Y) and lutetium-177 (177Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system. Methods: All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany). Sterile, GMP-certified, no-carrier added (NCA) 177Lu was used with GMP-certified peptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLC-SG and HPLC methods. R...
Australasian Physical & Engineering Sciences in Medicine, 2017
Skeletal uptake of β − emitters of DOTMP complexes is used for the bone pain palliation. In this study, two moderate energy β − emitters, 177 Lu (T 1/2 = 6.7 days, E βmax = 497 keV) and 175 Yb (T 1/2 = 4.2 days, E βmax = 480 keV), are considered as potential agents for the development of the bone-seeking radiopharmaceuticals. Since the specific activity of the radiolabelled carrier molecules should be high, the non-carrier-added (NCA) radionuclides have an effective role in nuclear medicine. Many researchers have presented the synthesis of NCA 177 Lu. Among these separation techniques, extraction chromatography has been considered more capable than other methods. In this study, a new approach, in addition to production of NCA 177 Lu by EXC procedure is using pure 175 Yb that was usually considered as a waste material in this method but because of high radionuclidic purity of 175 Yb produced by this method we used it for radiolabeling as well as NCA 177 Lu. To obtain optimum conditions, some effective factors on separation of Lu/Yb by EXC were investigated. The NCA 177 Lu and pure 175 Yb were produced with radionuclidic purity of 99.99 and 99.97% respectively by irradiation of enriched 176 Yb target in thermal neutron flux of 5 × 10 13 n/cm 2 s for 14 days. 177 Lu-DOTMP and 175 Yb-DOTMP were obtained with high radiochemical purities (> 95%) under optimized reaction conditions. Two radiolabeled complexes exhibited excellent stability at room temperature. Biodistribution studies in rats showed favorable selective skeletal uptake with rapid clearance from blood along with insignificant accumulation of activity in other non-target organs for two radiolabelled complexes.
Purpose [ 177 Lu]Lu-DOTATATE and [ 177 Lu]Lu-PSMA-617 used for targeted radionuclide therapy are very often prepared in the hospital radiopharmacy. The preparation parameters vary depending upon the specific activity of the 177 Lu used. The aim of this study was to develop optimized protocols to be used in the nuclear medicine department for the preparation of patient doses of the above radiopharmaceuticals. Method 177 Lu (CA and NCA) were used for radiolabeling DOTATATE and PSMA-617. Parameters studied are 177 Lu of different specific activity and different peptide concentrations and two different buffer systems. Paper and thin layer chromatography systems were used for estimating the radiochemical yield as well as radiochemical purity. Solid-phase extraction was used for the purification of the labeled tracers. Results [ 177 Lu]Lu-DOTATATE was prepared with CA 177 Lu (n = 13) and NCA 177 Lu (n = 6). Four batches each of [ 177 Lu] Lu-PSMA-617 were prepared using CA and NCA 177 Lu. Radiochemical yields > 80% and final product with less than < 1% radiochemical impurity could be obtained in all batches which were used for therapy. Conclusion Robust protocols for the preparation of clinical doses of [ 177 Lu]Lu-DOTATATE and [ 177 Lu]Lu-PSMA-617 were developed and used for the preparation of clinical doses. The quality of the SPECT images of both the tracers are consistent with the expected uptake in respective diseases.
Current Radiopharmaceuticals, 2014
Objective: Patient dose of 177 Lu-DOTA-TATE, used for providing radiotherapeutic treatment to the patients suffering from cancers of neuroendocrine origin, could be prepared at the hospital radiopharmacy either 'in-situ' or by using freezedried kits. The objective of the present work is to formulate and evaluate a single vial freeze-dried DOTA-TATE kit, which is capable of producing up to 7.4 GBq (200 mCi) dose of 177 Lu-DOTA-TATE and to compare the two methodologies presently used for the preparation of the agent. Experimental: Freeze-dried DOTA-TATE kits, comprising a lyophilized mixture of DOTA-TATE, gentisic acid and ammonium acetate, were prepared and used for the formulation of patient doses of 177 Lu-DOTA-TATE. The kits were subjected to detailed radiochemical evaluation and the shelf-life of the kits was determined. The pharmacokinetic behavior of the agent was studied in normal Wistar rats. These kits were utilized for treating the patients suffering from various types of neuroendocrine cancers. Results: The freeze-dried kits were used for the preparation of up to 7.4 GBq (200 mCi) therapeutic doses of 177 Lu-DOTA-TATE with a radiochemical purity of >99% and were found to have sufficiently long shelf-life. Biological studies carried out in normal Wistar rats exhibited no significant accumulation of activity in any of the vital organs/tissue except in kidneys and non-accumulated activity showed major renal clearance. Clinical studies carried out in cancer patients exhibited accumulation of activity in the cancerous lesions and metastatic sites. Conclusion: The kit was useful for the convenient preparation of therapeutic dose of 177 Lu-DOTA-TATE, suitable for human administration. The use of kit is expected to reduce the batch failure and radiation exposure to the working personnel.
American journal of nuclear medicine and molecular imaging, 2020
The present treatise chronicles one decade of experience pertaining to clinical PRRT services in a large-volume tertiary cancer care centre in India delivering over 4,000 therapies, an exemplar of successful PRRT programme employing indigenous 177Lutetium production and resources. For the purpose of systematic discussion, we have sub-divided the communication into 3 specific parts: (a) Radiopharmaceutical aspects that describes 177Lutetium production through 'Direct' Neutron Activation Route and the subsequent radiolabeling procedures, (b) The specific clinical nuances and finer learning points (apart from the routine standard procedure) based upon clinical experience and how it has undergone practice evolution in our setting and (c) Dosimetry results with this indigenous product and radiation safety/health physics aspects involved in PRRT services. Initiated in 2010 at our centre, the PRRT programme is a perfect example of affordable quality health care delivery, with indig...
Applied Radiation and Isotopes, 2007
177 Lu could be produced with a specific activity of 23,000mCi/mg(850GBq/mg)byneutronactivationusingenriched176Lu(64.323,000 mCi/mg (850 GBq/mg) by neutron activation using enriched 176 Lu (64.3%) target when irradiation was carried out at a thermal neutron flux of 1 Â 10 14 n/cm 2 /s for 21 d. 177 Lu-DOTA-TATE could be prepared in high radiochemical yield (23,000mCi/mg(850GBq/mg)byneutronactivationusingenriched176Lu(64.399%) and adequate stability using the 177 Lu produced indigenously. The average level of radionuclidic impurity burden in 177 Lu due to 177m Lu was found to be 250 nCi of 177m Lu/1 mCi of 177 Lu (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 mg (17.41 nmole) of DOTA-TATE and indigenously produced 177 Lu (0.8 mg, 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 mg of DOTA-TATE conjugate. This amount compares well with 177 Lu-DOTA-TATE prepared for a typical peptide receptor radionuclide therapy (PRRT) procedure which makes use of 100 mg of the DOTA-TATE conjugate, which incorporates 50 mCi (1.85 GBq) of 177 Lu activity, thereby implying that in order to achieve a single patient dose of 150-200 mCi (5.55-7.40 GBq), 300-400 mg of the conjugate needs to be used.
EJNMMI Research
Background: This study's aim was to develop our dosimetric methodology using a commercial workstation for the routine evaluation of the organs at risk during peptide receptor radionuclide therapy (PRRT) with 177 Lu. Methods: First, planar and SPECT sensitivity factors were determined on phantoms. The reconstruction parameters were optimized by SPECT/CT image acquisition using a NEMA IEC phantom containing a 500 ml bottle of 177 Lu, to simulate a kidney. The recovery coefficients were determined on various phantoms. For the red marrow, this was calculated using a NEMA IEC phantom that contained a centrally placed bottle of 80 ml of 177 Lu (to model the L2-L4 red marrow) flanked by two 200 ml bottles with 177 Lu to simulate the kidneys. Then, SPECT/CT images were acquired at 4, 24, 72, and 192 h after injection in 12 patients with neuroendocrine tumors who underwent PRRT with 177 Lu-DOTATATE. SPECT data were reconstructed using the iterative ordered subset expectation maximization (OSEM) method, with six iterations and ten subsets, attenuation, scatter, recovery resolution corrections, and a Gaussian post-filter of 0.11 cm. The liver, spleen, kidneys, and red marrow dose per administered activity (AD/A admin) values were calculated with the Medical Internal Radiation Dose (MIRD) formalism and the residence times (Dosimetry toolkit® application) using standard and CT imaging-based organ masses (OLINDA/EXM® V1.0 software). Results: Sensitivity factors of 6.11 ± 0.01 and 5.67 ± 0.08 counts/s/MBq were obtained with planar and SPECT/CT acquisitions, respectively. A recovery coefficient of 0.78 was obtained for the modeled L2-L4 red marrow. The mean AD/A admin values were 0.43 ± 0.13 mGy/MBq [0.27-0.91] for kidneys, 0.54 ± 0.58 mGy/MBq [0.12-2.26] for liver, 0. 61 ± 0.13 mGy/MBq [0.42-0.89] for spleen, and 0.04 ± 0.02 mGy/MBq [0.01-0.09] for red marrow. The AD/A admin values varied when calculated using the personalized and standard organ mass, particularly for kidneys (p = 1 × 10 −7), spleen (p = 0.0069), and red marrow (p = 0.0027). Intra-patient differences were observed especially in organs close to or including tumor cells or metastases. Conclusions: The obtained AD/A admin values were in agreement with the literature data. This study shows the technical feasibility of patient dosimetry in clinical practice and the need to obtain patient-specific information.