Production Of 177Lu Research Articles

Study of the production of radioisotopes at IFMIF-DONES: 177Lu with deuterons

The production of radioisotopes for nuclear medicine is boosted by different international agencies. The International Fusion Materials Irradiation Facility - Demo Oriented NEutron Source (IFMIF-DONES) will be a infrastructure for testing under high neutron flux the materials to be used in future DEMO fusion reactor. IFMIF-DONES will generate neutrons by means of the impact of a high-power deuteron beam onto a lithium-jet target. There is an important effort to take advantage of the outstanding characteristics of the facility in terms of neutrons and deuterons. Thus, a complementary program is being developed, where the production of radioisotopes for medicine is one of the main applications. Here, we discuss the production of 177Lu with deuterons at IFMIF-DONES.

Characterization and mapping of the neutron fields around Bruce Power’s 177Lu isotope production system

Bruce Power operates a first-of-its-kind isotope production system (IPS) that enables continuous production of 177Lu within Canada Deuterium Uranium (CANDU) commercial power reactors. Located on the reactivity mechanisms deck of Unit 7, just outside of reactor containment but in close proximity to the primary heat transport (PHT) pumps, this facility offers unique advantages for 177Lu production. However, employees working in this area encounter a radiation hazard which consists primarily of photoneutrons. These originate from the base of the PHT pumps and are only present when the reactor is operating. This study evaluates neutron exposure at Bruce Power’s IPS by using a nested neutron spectrometer (NNS) to determine the neutron energy spectra and absolute dosimetric quantities such as the ambient dose equivalent, H*(10). The results from the NNS are then compared to surveys performed by a portable neutron rem meter (Model NP-2 by Nuclear Research Corporation), routinely used by Bruce Power staff for workplace monitoring. While the Model NP-2 generally showed consistent results across locations, a 50% dose correction factor was identified when operators were harvesting 177Lu from the IPS. This finding highlights an opportunity to reduce the neutron dose that is assigned to operators when producing 177Lu.

Shape-persistent COF-derived functional carbon microspheres for No-carrier added 177Lu separation

Porous carbon materials stemming from covalent organic frameworks (COFs) have emerged as pivotal candidates in various fields. However, no COF or relevant derivative has stepped into the recovery of no-carrier added (NCA) 177Lu, one of the most important radionuclides in modern medicine, from irradiated target. In this work, shape-persistent COF-derived carbon microsphere (COF-CMS) was successfully synthesized via self-templated carbonization and subsequently functionalized with active component 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester (P507). The prepared functional COF-CMS@P507 has shown high selectivity and fast adsorption kinetics for Yb3+/Lu3+ in static batch adsorption and great potential in dynamic column separation of Lu3+ from Yb3+. More importantly, based on plenty of tracer experiments and practical investigations, a separation process flow was established to realize the isolation of 177Lu from an irradiated 176Yb target. Consequently, 177Lu product can be effectively obtained in preferable recovery (86%) with high radinuclidic and chemical purity (≥99.99%). The present study provides a new idea for NCA 177Lu production, which is also valuable for the development of lanthanide separation and functional COFs.

Study of the Medical Isotope 177Lu Production in Photonuclear Reactions on 178Hf-Enriched Targets

Study of the Medical Isotope 177Lu Production in Photonuclear Reactions on 178Hf-Enriched Targets

Whole process establishment of carrier-free 177Lu production: from small-scale production to pilot-scale production

Whole process establishment of carrier-free 177Lu production: from small-scale production to pilot-scale production

Optimization of Deuteron Irradiation of 176Yb for Producing 177Lu of High Specific Activity Exceeding 3000 GBq/mg.

The irradiation of 176Yb with deuterons offers a promising pathway for the production of the theranostic radionuclide 177Lu. To optimize this process, calculations integrating deuteron transport, isotope production, and decay have been performed. In pure 176Yb, the undesired production of 174g+mLu occurs at higher deuteron energies, corresponding to a distribution slightly shallower than that of 177Lu. Hence, 174g+mLu can be effectively filtered out by employing either a low-energy deuteron beam or stacked foils. The utilization of stacked foils enables the production of 177Lu using a high-energy linear accelerator. Another unwanted isotope, 176mLu, is produced roughly at the same depth as 177Lu, but its concentration can be significantly reduced by selecting an appropriate post-irradiation processing time, owing to its relatively short half-life. The modeling approach extended to the mapping of yields as a function of irradiation time and post-irradiation processing time. An optimized processing time window was identified. The study demonstrates that a high-energy deuteron beam can be employed to produce 177Lu with high specific activity exceeding 3000 GBq/mg. The effect of different purity levels (ranging from 98% to 100%) was also discussed. The impurity levels have a slight impact. The modeling demonstrates the feasibility of obtaining 177Lu with a specific activity > 3000 GBq/mg and radionuclidic purity > 99.5% when using a commercially available 176Yb target of 99.6% purity.

Thermal-hydraulic safety analysis of radioisotope production in HANARO using MCNP6 and COMSOL multiphysics: A feasibility study

The High-flux Advanced Neutron Application Reactor (HANARO) produces radioisotopes (RIs) (131I, 192Ir, etc.) through neutron irradiation on various RI production targets. Among them, 177Lu and 166Ho are particularly promising owing to their theranostic characteristics that facilitate simultaneous diagnosis and treatment. Prior to neutron irradiation, evaluating the nuclear heating of the RI production target is essential for ensuring the thermal-hydraulic safety of HANARO. In this study, the feasibility of producing 177Lu and 166Ho using irradiation holes of HANARO was investigated in terms of thermal-hydraulic safety. The nuclear heating rates of the RI production target by prompt and delayed radiation were calculated using MCNP6. The calculated nuclear heating rates were used as an input parameter in COMSOL Multiphysics to obtain the temperature distribution in an irradiation hole. The degree of temperature increase of the 177Lu and 166Ho production targets satisfied the safety criteria of HANARO. The nuclear heating rates and temperature distribution obtained through the in silico study are expected to provide valuable insight into the production of 177Lu and 166Ho using HANARO.

Neutronic simulation of medical radioisotope 99Mo and 177Lu production in IPR 14 MeV neutron generator facility

An accelerator based 14 MeV neutron generator is commissioned at Institute for Plasma Research India. The generator is based on the linear accelerator concept where the deuterium ion beam impinged to the tritium target to produce neutrons. The generator is designed to produce 5 × 1012 n/s (max.). The 14 MeV neutron source facilities are an emerging tool for the lab scale experiments and research. In order to utilize the generator for the welfare of humanity, the assessment is made for the production of medical radioisotopes using the neutron facility.The usage of radioisotopes in the treatment and diagnosis of a disease is an important factor in the healthcare sector. A series of calculations are conducted to generate radioisotopes, especially 99Mo and 177Lu those are having huge applications in the medical and pharmaceutical industries. 99Mo can be also generated through neutron reactions 98Mo(n, g)99Mo and 100Mo(n, 2n)99Mo apart from fission reaction. The cross section of 98Mo(n, g)99Mo is high in the thermal energy range whereas 100Mo(n,2n)99Mo occurs at a high energy range. 177Lu can be produced using the reactions 176Lu (n, g)177Lu and 176Yb (n, g)177Yb. The cross section of both 177Lu production routes is higher at thermal energy range. The neutron flux level near the target is around 1010 cm−2s−1. In order to enhance production capabilities, the neutron energy spectrum moderators are used to thermalize the neutrons. The materials used as a moderator are beryllium, HDPE, graphite, etc. Moderators enhance the capabilities of medical isotope production in neutron generators.

Recovery of 177Lu from Irradiated HfO2 Targets for Nuclear Medicine Purposes.

A new method of production of one of the most widely used isotopes in nuclear medicine, 177Lu, with high chemical purity was developed; this method includes irradiation of the HfO2 target with bremsstrahlung photons. The irradiated target was dissolved in HF and then diluted and placed onto a column filled with LN resin. Quantitative sorption of 177Lu could be observed during this process. The column later was rinsed with the mixture of 0.1 M HF and 1 M HNO3 and then 2 M HNO3 to remove impurities. Quantitative desorption of 177Lu was achieved by using 6 M HNO3. The developed method of 177Lu production ensures high purification of this isotope from macroquantities of hafnium and zirconium and radioactive impurities of carrier-free yttrium. The content of 177mLu in 177Lu in photonuclear production was determined. Due to high chemical and radionuclide purity, 177Lu obtained by the developed method can be used in nuclear medicine.

Stability in the production and transport of 177Lu labelled PSMA

The prostate cancer is the second most prevalent disease among men in Brazil, moreover PSMA therapy could change this scenario and its perspectives. IPEN-CNEN is the Brazilian industrial radiopharmacy center that produces radiopharmaceuticals for therapy. The production of 177Lu-PSMA-617 was evaluated in batches until 37 GBq and showed that the combination of ascorbate buffer, adequate radioactive concentration and freezing promoted the stability of the radiopharmaceutical for 48 hours, enabling transport of 177Lu-PSMA-617 to distant regions of the country.

Investigation of Radiolabeling Efficacy by Enhancement of the Chemical form of no Carrier Added 177Lu Isolated by Electro Amalgamation Process.

Due to the suitable nuclear decay characteristics, 177Lu is an attractive radionuclide for various therapeutic applications. The non-carrier added form of177Lu has drawn much attention because of its high specific activity needed in radiolabeling studies. There have been several separation methods for NCA177Lu production. Among the various separation methods, the electro-amalgamation separation method has got a large potential for large scale production. Li presence is a significant problem in this separation method, which seriously affects the radiolabeling efficiency. In this study, Li was separated from the final product of electro-amalgamation separation by adding an ion-exchange chromatography column to the separation process. NCA 177Lu was obtained by 84.09% ELM separation yield, 99.9% radionuclide purity and, 65 Ci/g specific activity. Then, 177Lu (177LuCl3 chemical form) was separated from Li using the ion exchange chromatography method by a separation yield of 94%. The obtained results of the radiolabeling efficacy studies showed that the radiochemical purity and radio-complex stability were significantly increased by separating NCA 177Lu from Li. This new separation setup consisting of two steps allows using 177Lu of such a favorable quality for labeling studies.

Optimization of Reaction Parameters for the Synthesis of 177Lu-DOTAELA

The article provides a comparison of the theoretically calculated and experimentally determined yield of the reaction 176Lu (n, �A)177Lu. Also, it provides the results of the studies on lutetium-177 labeling of a non-peptide antagonist of gonadotropin-releasing hormone (GnRH) elagolix (ELA) associated with a chelating DOTA (DOTAELA). The synthesized DOTAELA complex was labeled with the 177Lu isotope.177Lu was produced by the reaction (n, �A) using the enriched LuCl3 target at the reactor WWR�CK. Production of 177Lu by the (n, �A) reaction from the enriched 176Lu target achieved by irradiation for 17 days. All stages of the complex preparation were evaluated by paper chromatography. The optimal technological parameters for the synthesis of the complex 177Lu-DOTAELA are: pH - 4.5, 90-100 �aC and 40 min. The obtained optimal parameters made it possible to produce a labeled complex of 177Lu�CDOTAELA with a radiochemical yield of �Y 95%.

Modelling of the 177mLu/177Lu radionuclide generator

In order to determine the potential of 177mLu/177Lu radionuclide generator in 177Lu production it is important to establish the technical needs that can lead to a clinically acceptable 177Lu product quality. In this work, a model that includes all the processes and the parameters affecting the performance of the 177mLu/177Lu radionuclide generator has been developed. The model has been based on the use of a ligand to complex 177mLu ions, followed by the separation of the freed 177Lu ions. The dissociation kinetics of the Lu-ligand complex has been found to be the most crucial aspect governing the specific activity and 177mLu content of the produced 177Lu. The dissociation rate constants lower than 1*10-11 s-1 would be required to lead to onsite 177Lu production with specific activity close to theoretical maximum of 4.1 TBq 177Lu/mg Lu and with 177mLu content of less than 0.01%. Lastly, the calculations suggest that more than one patient dose per week can be supplied for a period of up to 7 months on starting with the 177mLu produced using 3 g Lu2O3 target with 60% 176Lu enrichment. The requirements of the starting 177mLu activity production needs to be adapted depending on the required patient doses, and the technical specifications of the involved 177mLu-177Lu separation process.

Estimation of 47Sc and 177Lu production rates from their natural targets in Kyoto University Research Reactor

Estimation of 47Sc and 177Lu production rates from their natural targets in Kyoto University Research Reactor

Radionuclide generator-based production of therapeutic\xa0177Lu from its long-lived isomer 177mLu

BackgroundIn this work, a lutetium-177 (177Lu) production method based on the separation of nuclear isomers, 177mLu & 177Lu, is reported. The 177mLu-177Lu separation is performed by combining the use of DOTA & DOTA-labelled peptide (DOTATATE) and liquid-liquid extraction.MethodsThe 177mLu cations were complexed with DOTA & DOTATATE and kept at 77 K for periods of time to allow 177Lu production. The freed 177Lu ions produced via internal conversion of 177mLu were then extracted in dihexyl ether using 0.01 M di-(2-ethylhexyl) phosphoric acid (DEHPA) at room temperature. The liquid-liquid extractions were performed periodically for a period up to 35 days.ResultsA maximum 177Lu/177mLu activity ratio of 3500 ± 500 was achieved with [177mLu]Lu-DOTA complex, in comparison to 177Lu/177mLu activity ratios of 1086 ± 40 realized using [177mLu]Lu-DOTATATE complex. The 177Lu-177mLu separation was found to be affected by the molar ratio of lutetium and DOTA. A 177Lu/177mLu activity ratio up to 3500 ± 500 was achieved with excess DOTA in comparison to 177Lu/177mLu activity ratio 1500 ± 600 obtained when lutetium and DOTA were present in molar ratio of 1:1. Further, the 177Lu ion extraction efficiency, decreases from 95 ± 4% to 58 ± 2% in the presence of excess DOTA.ConclusionThe reported method resulted in a 177Lu/ 177mLu activity ratio up to 3500 after the separation. This ratio is close to the lower end of 177Lu/177mLu activity ratios, attained currently during the direct route 177Lu production for clinical applications (i.e. 4000–10,000). This study forms the basis for further extending the liquid-liquid extraction based 177mLu-177Lu separation in order to lead to a commercial 177mLu/177Lu radionuclide generator.

Production of Lutetium-177: Process Aspects

Papers dealing with the 177Lu production technology are analyzed with the aim of evaluating the readiness of the existing processes to setting up regular large-scale production, which is the necessary condition for the progress of the market of 177Lu-based radiopharmaceuticals. This is now on the initial step of its development. The 177Lu production processes are based on irradiation of isotopically enriched 176Lu or 176Yb with reactor neutrons, followed by radiochemical processing of the irradiated targets. Specific production features are analyzed with emphasis on process aspects of the reactor and radiochemical stages. The evaluation shows that the presently reached level of the 177Lu production technology allows only the current demand of nuclear medicine for this radionuclide, corresponding to the initial step of its clinical use, to be met. Further growth of the market of 177Lu radiopharmaceuticals requires the upgrading of existing or construction of new facilities, which is possible only with significant improvement of both reactor and radiochemical processes.

177Lu Accumulation Parameters in Different Nuclear Reactors

A computational study of 177Lu production in the neutron spectra of 26 nuclear research reactors was performed by two methods: from 176Lu and 176Yb. It is shown that the production of 177Lu from 176Lu with satisfactory specific activity ~7.4·105 GBq/g and higher can be accomplished only in reactors with thermal neutron flux density not less than 1014 sec–1·cm–2. Under long-duration irradiation, not only is the specific activity of the desired isotope reduced but the contribution of 177mLu in the activity increases, as a result of which the quality of the final product is lowered. The accumulation of 177Lu from 176Yb makes it possible to obtain high specific activity in all research reactors and requires using targets with high enrichment with 176Yb and minimum content of 174Yb. In addition, most importantly, the specific activity decreases under irradiation in reactors with high thermal neutron flux density, first and foremost, in SM and HFIR research reactors.

Production of Lu-177 Radionuclide using Deuteron Beams: Comparison between (d,n) and (d,p) Nuclear Reactions

Lutetium-177 (177Lu) radioisotope has been suggested for radioimmunotherapy application in nuclear medicine. Presently 177Lu has been mostly produced using neutron activation in nuclear reactors, whereas cyclotron-based production has not been well explored. In this paper, we theoretically propose cyclotron-based deuteron beams for 177Lu production. By Employing the TALYS 2017 codes, we calculated nuclear cross-sections and the End-of-Bombardment (EOB) yields of 176Yb(d,n) 177Lu reaction for direct production of 177Lu as well as 176Yb(d,p)177Yb→177Lu reaction for indirect production of 177Lu. The TALYS calculated cross-sections indicated that the threshold energy of both investigated nuclear reactions is 0 MeV; thus 177Lu could be produced at low deuteron energy bombardment, though significant amount of 177Lu radioactivity could only be generated for deuteron beams with energy greater than 6 MeV. The calculated EOB yields for 176Yb(d,n)177Lu reaction and 176Yb(d,p)177Yb reaction were 0.519 and 181.1 MBq/μAh respectively, which well agreed with previous experimental results published elsewhere. In conclusion, both nuclear reactions are possible for 177Lu production though the indirect method via 176Yb(d,p)177Yb→177Lu reaction would give much better EOB yield than that of direct method.

Production of 177Lu by hafnium irradiation using 55-MeV bremsstrahlung photons

The possibility of production a medical radionuclide 177Lu by irradiating natHfO2 by bremsstrahlung photons up to 55 MeV was investigated. The yields of the main nuclear reactions were measured. A procedure for one-step separation of carrier free 177Lu via extraction chromatography on the LN resin sorbent (Triskem) was developed. The radiochemical yield was 98%, separation factor was higher than 105. Isomeric ratio 177mLu/177Lu was estimated. Simulation of 177Lu production in photonuclear reactions on 178Hf, 179Hf and natHf nuclei was performed. The possibility of production of medical quantities was discussed.

Feasibility study for production and quality control of Yb-175 as a byproduct of no carrier added Lu-177 preparation for radiolabeling of DOTMP.

Skeletal uptake of β- emitters of DOTMP complexes is used for the bone pain palliation. In this study, two moderate energy β- emitters, 177Lu (T1/2 = 6.7days, Eβmax = 497keV) and 175Yb (T1/2 = 4.2days, Eβmax = 480keV), 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 177Lu. 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 177Lu by EXC procedure is using pure 175Yb that was usually considered as a waste material in this method but because of high radionuclidic purity of 175Yb produced by this method we used it for radiolabeling as well as NCA 177Lu. To obtain optimum conditions, some effective factors on separation of Lu/Yb by EXC were investigated. The NCA 177Lu and pure 175Yb were produced with radionuclidic purity of 99.99 and 99.97% respectively by irradiation of enriched 176Yb target in thermal neutron flux of 5 × 1013n/cm2 s for 14days. 177Lu-DOTMP and 175Yb-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.