Target Irradiation Research Articles

Sustainable production of radionuclidically pure antimony-119

BackgroundRadiopharmaceutical therapy (RPT) uses radionuclides that decay via one of three therapeutically relevant decay modes (alpha, beta, and internal conversion (IC) / Auger electron (AE) emission) to deliver short range, highly damaging radiation inside of diseased cells, maintaining localized dose distribution and sparing healthy cells. Antimony-119 (119Sb, t1/2 = 38.19 h, EC = 100%) is one such IC/AE emitting radionuclide, previously limited to in silico computational investigation due to barriers in production, chemical separation, and chelation. A theranostic (therapeutic/diagnostic) pair can be formed with 119Sb’s radioisotopic imaging analogue 117Sb (t1/2 = 2.80 h, Eγ = 158.6 keV, Iγ = 85.9%, β+ = 262.4 keV, Iβ+ = 1.81%).ResultsWithin, we report techniques for sustainable and cost-effective production of pre-clinical quality and quantity, radionuclidically pure 119Sb and 117Sb, novel low energy photon measurement techniques for 119Sb activity determination, and physical yields for various tin target isotopic enrichments and thicknesses using (p, n) and (d, n) nuclear reactions. Additionally, we present a two-column separation providing a radioantimony yield of 73.1% ± 6.9% (N = 3) and tin separation factor of (6.8 ± 5.5) x 105 (N = 3). Apparent molar activity measurements for deuteron produced 117Sb using the chelator TREN-CAM were measured at 42.4 ± 25 MBq 117Sb/µmol (1.14 ± 0.68 mCi/µmol), and we recovered enriched 119Sn target material at a recycling efficiency of 80.2% ± 5.5% (N = 6) with losses of 11.6 mg ± 0.8 mg (N = 6) per production.ConclusionWe report significant steps in overcoming barriers in 119Sb production, chemical isolation and purification, enriched target material recycling, and chelation, helping promote accessibility and application of this promising therapeutic radionuclide. We describe a method for 119Sb activity measurement using its low energy gamma (23.87 keV), negating the need for attenuation correction. Finally, we report the largest yet-measured 119Sb production yields using proton and deuteron irradiation of natural and enriched targets and radioisotopic purity > 99.8% at end of purification.

Spatial-temporal modulation method of nanosecond laser for the double-cone ignition scheme

In order to improve the stability of the pulse, realize the high requirements of the direct drive ignition design for the uniformity of the target irradiation, reduce the interference of laser plasma instability, and improve the laser-target coupling efficiency, a nanosecond laser spatial-temporal modulation of high-power laser driver for double-cone ignition (DCI) research was proposed. Under the premise of satisfying the near-isentropic compression waveform of driving implosion, the time-power curves of all sub-beams in the facility are redistributed to reduce the waveform contrast ratio of each sub-beam. A fewer number of sub-beams are utilized to generate low-power foot pulses, which are focused on the target surface of the initial radius. And the remaining sub-beams are utilized to generate high-power driving main pulses, which are focused on a relatively small target surface. It is shown that the stability of the time-power curve of each sub-beam and the power balance control ability can be effectively improved by redistributing. At the same time, the variable focal spot control can be realized to reduce the influence of cross-beam energy transfer (CBET).

Measurement of electromagnetic pulse in laser acceleration enhanced by near-critical density targets

High-power laser interactions with solid targets create an abundance of high-energy charged particles, resulting in the generation of intense electromagnetic pulses (EMPs), which are strongly pertinent to the target parameters. In this study, the characteristics of EMPs generated by relativistic femtosecond laser irradiation of double-layer targets composed of near-critical density carbon nanotube foams (CNFs) and an aluminum (Al) foil are investigated. The results demonstrate that the CNF double-layer targets accelerate proton energy by over 1.6 times compared to a single-layer Al plane target, thereby indirectly amplifying the EMP amplitude by over 3.6 times. The findings are beneficial to gaining insight into EMPs induced by femtosecond laser coupling with near-critical density targets and open a new avenue to achieve tunable EMPs by managing the material and structure of the target to optimize the coupling efficiency between the laser and solid targets.

Simultaneous Production of 111In and 109Cd by Alpha Particle Irradiation of natAg Target and Synergistic Aqueous Biphasic Separation using Green Tea Polyphenols

Abstract111In and 109Cd radionuclides were produced by 31 MeV ‐particle irradiation of natAg target. To separate no‐carrier added (NCA) 111In and 109Cd from bulk Ag, Aqueous Biphasic System (ABS) was constructed using twelve salts and two polyethylene glycol (PEG) combinations. Out of all these combinations, only three salts e. g., Na2SO3, Na‐ malonate and Na‐Tartrate and PEG combinations showed significant separation between bulk Ag and NCA radioisotopes. Addition of catechins extracted from green tea to the above ABS systems increased the separation factors many folds. Highest separation factor (SIn/Ag=5.6×104) for 111In was obtained in Na2SO3‐PEG 4000 and 50 mg catechins system. 109Cd retained in NCA state in the Na‐malonate phase after the extraction of 111In and bulk Ag in the catechin‐PEG phase.

The spatio-temporal evolution of shock wave pressure induced by laser: Effects of laser parameters and confinement layer

The spatio-temporal distribution of the shock wave pressure on the surface of the target is the key to the performance of laser shock processing (LSP), which is mainly determined by the laser parameters and the confinement layer. The two-dimensional kinetic simulations of the expansion process of the shock wave induced by irradiation of an aluminum target with nanosecond laser pulses are performed. It is found that by controlling the gap between the rigid confinement layer and the aluminum target, and the interval time between the double pulse laser pulses, multiple peaks appear on the shock wave pressure-time curve of the aluminum target surface, and the value and interval time of each peak will change.

Iron-based magnetic nanocomplexes for combined chemodynamic and photothermal cancer therapy through enhanced ferroptosis

Chemodynamic therapy (CDT) guided by Fenton chemistry and iron-containing materials can induce ferroptosis as a prospective cancer treatment method, but the inefficient Fe3+/Fe2+ conversion restricts the monotherapeutic performances. Here, an iron-based nanoplatform (Fe3O4-SRF@FeTA) including a magnetic core and a reductive film is developed for combined CDT and photothermal therapy (PTT) through ferroptosis augmentation. The inner iron oxide core serves as a photothermal transducer, a magnet-responsive module, and an iron reservoir for CDT. The coated Fe3+-tannic acid film (FeTA) provides extra iron and reductants for Fe3+/Fe2+ conversion acceleration, and functions as a door keeper for the pH- and light-responsive release of the embedded ferroptosis inducer sorafenib (SRF). The in vitro results demonstrate that the iron-based nanocomplexes promote the production of lipid peroxide through the amplified Fenton activity, and downregulate glutathione involved in lipid peroxide repair system through the responsively released SRF. Upon accumulation in tumor by magnetic targeting and sequential laser irradiation locoregionally, Fe3O4-SRF@FeTA nanocomplexes present prominent in vivo anticancer efficacy by leveraging PTT and CDT-enhanced ferroptosis.

Development of Target Holder for the First Experiment on an Alternative Route for 64Cu Radioisotope Production by Secondary Neutron Irradiation of a 64ZnO Target

The target holder, as part of the target system for cyclotron-based radioisotope production, plays a crucial role in successful radioisotope production. The target holder has to be designed and developed so that it will not deform or melt should a beam of energetic particles irradiate the target. In this work, we develop and test a target holder for 64Cu radioisotope production. The thermal distribution and structural analysis are simulated using ANSYS software. Based on the ANSYS simulation results, a maximum temperature of 84°C occurred on the titanium foil, while the maximum temperature in the target holder body was 35.6°C when an 11-MeV proton beam with a beam current of 25 μA was bombarded on the target holder. We successfully test the target holder, and for the first time, we experimentally produce a 64Cu radioisotope by secondary neutron irradiation of the 64ZnO target. Using 11-MeV protons with a proton beam current of 25 μA incident on a 1-mm Ti foil for 5 min, we were able to generate secondary neutrons, and then the secondary neutrons irradiated 1 g of the enriched 64ZnO target. Copper-64 produced from the 64Zn(n,p)64Cu nuclear reaction was eventually detected using a portable gamma spectrometer, and its radioactivity was measured using a dose calibrator. For the first time, this experimental study confirmed that as much as 48.8 ± 6.2 MBq/μAh radioactivity of 64Cu was produced with no observed radioactive impurities.

Evaluation of Inverse Planned and Forward Planned Intensity Modulated Radiotherapy Techniques in Breast Cancer

Introduction: The objective of this study is to compare the dosimetric parameters of radiation to the whole breast between the two intensity-modulated radiotherapy (IP IMRT) techniques, i.e. Inverse planned IMRT (IP IMRT) and Forward Planned IMRT (FP IMRT) with regard to target coverage (PTV) and irradiation of organs at risk (OAR). Material and Methods: Plain and Contrast enhanced computed tomography (CECT) datasets were created for 41 patients treated with whole breast radiation therapy. CT simulation and treatment is performed using deep inspiratory breath hold technique (DIBH). Radiotherapy treatment Planning is done using Eclipse Treatment Planning System (version 13.7) with a prescription dose of 40 Gy in 15#. The developed treatment plans were subjected to objective comparison of PTV and OARs using dose volume histograms (DVH). Results: IP IMRT plans provided better coverage (99.5% vs 97.6%), comparable though higher maximum dose (Dmax 45.0 VS 44.1 Gy), higher hot spot (PTV105% 49.2 vs 33), lower volumes receiving 20, 25, 30 Gy (V20, V25, V30) for heart, more homogeneous (homogeneity index 0.10 vs. 0.14) and conformal dose distribution (conformity Index 1.0 vs 0.98) compared to FP IMRT. Regarding OAR dosimetry it is observed that FP IMRT showed reduced mean dose to Coronary artery (LADCA), Contralateral Lung (CL), Contralateral breast (CB) along with reduction in low dose region (V5) to all OARs under study. It was also observed that Monitor units used and planning time were lower for FP IMRT. Conclusion: On weighing different dosimetric factors, both the techniques have displayed their own advantages and disadvantages. Choosing a planning technique needs to be customized taking into consideration various factors such as breast topography, size and volumes of breast, availability of expertise planning skills and resources.

Radiochemical separation of 161 Tb from neutron irradiated Gd target by liquid-liquid extraction technique

Abstract No-carrier-added (NCA) 161 Tb, which has advisable nuclear properties to be applied for cancer radiotherapy was produced at the Egyptian Second Research Reactor (ETRR-2) by neutron irradiation of natural gadolinium target via indirect nuclear reaction. The radiochemical separation of 161 Tb from irradiated gadolinium target was investigated based on solvent extraction technique using Cyanex 302. Several separation parameters were checked and optimized. According to the obtained results, the separation process of the investigated radioisotopes proceeds in two steps. The first step is an extraction of all of them into the organic phase in which the extraction % (98 %) was optimized at pH 4, 0.15 M of Cyanex 302 and 2.5 h extraction time. Moreover, the slope analysis method confirmed the participation of 2 mol of the organic extractant for the separation of 161 Tb from irradiated gadolinium. The second step is the separation of the 161 Tb isotope that was purified by the stripping of 159Gd with a citrate solution at pH 9, which is considered as a highly efficient and promising method for separation and purification of the two radioisotopes.

Shock melt in the Cold Bokkeveld CM2 carbonaceous chondrite and the response of C‐complex asteroids to hypervelocity impacts

AbstractMany of the CM carbonaceous chondrites are regolith breccias and so should have abundant evidence for collisional processing. The constituent clasts of these fragmental rocks frequently display compactional petrofabrics; yet, olivine microstructures show that most CMs are unshocked. To better understand the reasons for this contradiction, we have sought other evidence for hypervelocity impact processing of CM chondrites using the Cold Bokkeveld meteorite. We find that this regolith breccia contains rare particles of vesicular shock melt that are close in chemical composition to bulk CM chondrite. Transmission electron microscopy of a melt bead shows that it is composed of silicate glass with inclusions of pentlandite, pyrrhotite, and wüstite. Characterization of shards of another bead by atom probe tomography reveals nanoscale clusters of sulfur that represent sulfide inclusions arrested at an early stage of growth. These glass particles are mineralogically comparable to micrometeoroid impact melt described from the Cb‐type asteroid Ryugu and melt that has been experimentally produced by pulsed laser irradiation of CM targets. The glass could have formed by in situ shock‐melting, but petrographic evidence is more consistent with an origin as ballistic ejecta from a distal impact. The scarcity of melt in this meteorite, and CM chondrites more broadly, is consistent with the explosive fragmentation of hydrous asteroids following energetic collisions. Cold Bokkeveld's parent body is likely to be a second‐generation asteroid that was constructed from the debris of one or more earlier bodies, and only a small proportion of the reaccreted material had been highly shocked and melted.

PDL1/HER2-Targeted Lipid-Encapsulated Oxygen Nanobubbles Combined with Photodynamic Therapy for HER2+ Breast Cancer Immunotherapy.

Programmed death (PD) 1/PD ligand 1 (PDL1) inhibitors are immune checkpoint inhibitors (ICIs) that may facilitate HER2-positive breast cancer treatment; however, their clinical efficacy remains elusive. Oxygen-enhanced photodynamic therapy (PDT) increases immunogenic cell death (ICD), providing a promising strategy to render the tumor microenvironment more sensitive to the ICIs. Lipid-encapsulated oxygen nanobubbles (Lipo-NBs-O2) obtained using nanobubbles (NBs) water for oxygen delivery in vivo can facilitate enhanced PDT. Here, dual-receptor targeted Lipo-NBs-O2 (DRT@Lipo-NBs-O2) is prepared by modifying Lipo-NBs-O2 with anti-PDL1 scFv and the fusion protein anti-HER2 scFv-tandem-repeat cytochrome c (anti-HER2-nCytc). Copper phthalocyanine is the photosensitizer (PS). DRT@Lipo-PS-NBs-O2 plus near-infrared irradiation leads to robust ICD induction, increasing DC activation and CD8+ T-cell numbers. Modification with anti-PDL1 scFv improves tumor distribution of DRT@Lipo-PS-NBs-O2 and plays the ICI role, invigorating CD8+ T cells and boosting the effects of immunotherapy. Oxygen supplied through DRT@Lipo-PS-NBs-O2 reduces P-glycoprotein expression. Enhanced PDT and Cytc can cause tumor cell death, thereby reducing the immune burden. Under dual receptor targeting and laser local irradiation, tumor cells become subject to the combination effects of PDT, ICD, ICIs, and apoptosis; this effectively suppresses tumor growth and metastasis. Lipo-NBs-O2 affords a combination of oxygen delivery and multidrug therapy to alleviate HER2-positive breast cancer.

Cross section measurements for the production of 49,51Cr and 47Sc from proton irradiation of natural vanadium up to 24 MeV

Scandium-47 is a promising radionuclide for targeted radiotherapy and is also an elementally matched therapeutic partner to 43Sc and 44Sc, which are suitable for Positron Emission Tomography. The predominantly reported routes for the production of 47Sc employ expensive enriched titanium or calcium targets to achieve high radionuclidic purity. This study reports measurements of the excitation function of the natV(p,x)47Sc reaction at proton energies of 18–24 MeV to optimize bombardment parameters for the production of 47Sc using this promising approach. The cross-sections reported here demonstrate that irradiation of vanadium targets can produce >99% radionuclidically pure 47Sc with a proton energy of 24 MeV, albeit at modest yields.

Improved Production of Novel Radioisotopes with Custom Energy Cyclone® Kiube

The implementation of the Variable Energy (VE) feature in the previously fixed-energy IBA Cyclone® Kiube cyclotron is presented as an upgrade enabling the production of novel radioisotopes with improved radionuclidic purity and production yields. The possibility of easily decreasing the energy of the extracted proton beam, from 18 down to 13 MeV, allows us to avoid the use of degraders and/or thick target windows, thus preventing related beam current limitations. The immediate application of the Variable Energy feature is proven by presenting the improved results obtained for the production of 68Ga from the irradiation of liquid targets simultaneously in terms of radionuclidic purity and activity produced.

Dimensional effects in analysis of laser-induced-desorption diagnostics data

The accurate assessment of the local tritium concentration in the tokamak first wall by means of the laser-induced desorption (LID) diagnostics is sought as one the key solutions to monitoring the local radioactive tritium content in the first wall of the fusion reactor ITER. Numerical models of gas desorption from solids used for LID simulation are usually closed with the one-dimensional transport models. In this study, the temperature and particle dynamics in the target irradiated by a short laser pulse during LID are analyzed by means of the two-dimensional model to assess the validity of using one-dimensional approximation for recovering the diagnostics signal. The quantitative estimates for the parameters governing the heat and particle transfer are presented. The analytical expressions for the sample spatiotemporal temperature profiles driven by the target irradiation with a Gaussian laser beam with the trapezoid temporal shape are derived. The obtained relations are used to simulate tritium desorption from a tungsten sample driven by pulsed heating. It is shown that depending on the ratio between the laser spot radius and the heat diffusion length, the one-dimensional approach can noticeably overestimate the sample temperature in the limit of small laser spot radius (estimated for tungsten as ∼0.5–1.0 mm), resulting in more than 100% larger amounts of tritium desorbed from the target, compared to the two-dimensional approximation. In the limit of large laser spot radius (≥1.5 mm), both approaches yield comparable amounts of tritium desorbed from the sample.

A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy

Objective. To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy. Approach. Phantoms of polyethylene, gelatin, or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent 11C, 10C and 15O radionuclides contributions in each voxel were determined from the extracted time activity curves. Next, the experimental configurations were simulated in Geant4 Monte Carlo versions 10.0 to 11.1, with three different fragmentation models—binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 model-version combinations. Total positron annihilation and parent isotope production yields predicted by each simulation were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Finally, we compared the depth of the maximum positron annihilation yield and the distal point at which the positron yield decreases to 50% of peak between each model and the experimental results. Main results. Performance varied considerably across versions and models, with no one version/model combination providing the best prediction of all positron-emitting fragments in all evaluated target materials and irradiation conditions. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions. Significance. The best predictions of the spatial distribution of positron annihilations and positron-emitting fragment production along the beam path during carbon and oxygen ion therapy was obtained using Geant4 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research.

Generation of plasma from multiple targets by laser ion source for TIARA ion implanter

We investigated a laser ion source for use as an ion source for the ion implanter in Takasaki Ion Accelerators for Advanced Radiation Application to increase the number of ion species that can be produced and to enable rapid switching of ion species. Herein, we analyzed the charge state distribution of ions in a laser plasma generated through irradiation of graphite, titanium, copper, and tantalum targets with 30 mJ Nd:YAG laser to determine the particle number of low-charge ions per pulse at 1.1 m from the target. The particle number of singly charged ions could be increased by adjusting the laser power density. For carbon, titanium, and tantalum, the particle numbers were in the order of 1010 ions per pulse, whereas for copper, the particle numbers were in the order of 109, lower than for other target materials.

Modeling of Integral Radiobiological Criteria for Simultaneous Irradiation of Multiple Targets with Different Absorbed Total Doses

Purpose: The paper is devoted to the comparison of simultaneous (SIB) and sequential (SEQ) radiation therapy of primary-multiple tumors with different absorbed total doses based on the modeling of integral radiobiological criteria. The research is aimed at optimization of treatment of rare primary-multiple tumors, development of optimal approaches based on the analysis of the effectiveness of different irradiation options. Material and methods: This research considers a system of primary-multiple targets, using a gynecologic tumor including vagina (adenosquamous carcinoma), endometrium (moderately differentiated adenocarcinoma with foci of squamous metaplasia), and lymph nodes as an example, to which certain equivalent total doses of irradiation must be delivered (EQD2>=74.8 Gy for vagina, EQD2>=85 Gy for endometrium). Different scenarios of two-stage and one-stage irradiation, including different combinations and doses for each target, are studied in the simulation. Results: Comparison of treatment plans for the triple target system shows that, performing sequential radiotherapy SEQ is characterized by higher levels of equivalent total dose delivered to the target volumes taking into account the total irradiation time and, consequently, to the critical organ volumes, especially in the rectum and sigmoid colon. In case of simultaneous irradiation SIB, the duration of treatment is five weeks instead of seven weeks, which reduces the value of the equivalent total dose to the target by 7-10 Gy. The value of the absorbed single dose delivered to the target volume is up to 3 Gy, which can be attributed to moderate hypofractionation. Levels of radiation exposure for critical organs in this case are much lower than when two-stage irradiation is used. Conclusion: Simultaneous integrated boost radiation therapy allows a significant reduction in radiation exposure to critical organs compared to sequential radiation therapy (reduction to single systems).

Neurotensin (8-13) and Neuromedin N Neuropeptides Radiolabelling with Copper-64 Produced on Solid or Liquid Targets.

On the verge of a theranostic approach to personalised medicine, copper-64 is one of the emerging radioisotopes in nuclear medicine due to its exploitable nuclear and biochemical characteristics. The increased demand for copper-64 for preclinical and clinical studies has prompted the development of production routes. This research aims to compare the (p,n) reaction on nickel-64 solid versus liquid targets and evaluate the effectiveness of [64Cu]CuCl2 solutions prepared by the two routes. As new treatments for neurotensin receptor-overexpressing tumours have developed, copper-64 was used to radiolabel Neurotensin (8-13) and Neuromedin N. High-quality [64Cu]CuCl2 solutions were prepared using ACSI TR-19 and IBA Cyclone Kiube cyclotrons. The radiochemical purity after post-irradiation processing reached 99% (LT) and 99.99% (ST), respectively. The irradiation of a solid target with 11.8 MeV protons and 150 μAh led to 704 ± 84 MBq/μA (17.6 ± 2.1 GBq/batch at EOB). At the end of the purification process (1 h, 90.90% activity yield), the solution for peptide radiolabelling had a radioactive concentration of 1340.4 ± 70.1 MBq/mL (n.d.c.). The irradiation of a liquid target with 16.9 MeV protons and 230 μAh resulted in 3.7 ± 0.2 GBq/batch at EOB, which corresponds to an experimental production yield of 6.89 GBq.cm3/(g.µA)sat. Benefiting from a shorter purification process (40 min), the activity yielded 90.87%, while the radioactive concentration of the radiolabelling solution was lower (492 MBq/mL, n.d.c.). The [64Cu]CuCl2 solutions were successfully used for the radiolabelling of DOTA-NT(8-13) and DOTA-NN neuropeptides, resulting in a high RCP (>99%) and high molar activity (27.2 and 26.4 GBq/μmol for LT route compared to 45 and 52 GBq/μmol for ST route, respectively). The strong interaction between the [64Cu]Cu-DOTA-NT(8-13) and the colon cancerous cell lines HT29 and HCT116 proved that the specificity for NTR had not been altered, as shown by the uptake and retention data.

The eighth SINQ Target Irradiation Program, STIP-VIII

The eighth experiment of the SINQ Target Irradiation Program (STIP-VIII) included a total of 941 specimens from 25 steels, 8 zircaloys, 6 tungsten based alloys (W-alloys) and 2 silicon carbide (SiC) composites. Specimens were prepared in 2016 and 2017. Irradiation was carried out in SINQ Target-13 in two periods: June 26 to December 21, 2018 and July 30 to December 23, 2020. The total proton charge received by Target-13 is 7.8 Ah, corresponding to 1.75×1023 protons. The irradiated specimens were unpacked in 2022 and 2023 and more than 98 % of the specimens were recovered. The specimens were irradiated at temperatures between 100 and 450 °C. The maximum doses are 10.4 dpa for steels, 14.8 dpa for zircaloys, 11.5 dpa for W-alloys, and 3.5 dpa for SiC composites. The He-to-dpa ratio is in the range of 22–42 appm/dpa for steels, 13–16 appm/dpa for zircaloys, 30–36 appm/dpa for W-alloys and 90–125 appm/dpa for SiC composites.

Improved purification of cyclotron [68Ga]GaCl3 for the production of 68Ga radiopharmaceuticals

IntroductionIncreased demand for NetSpot and Illuccix as requirement to receive the respective Lutathera and Pluvicto radiotherapies, and monitor subsequent response to treatment, have reinforced the need to develop alternative ways of producing gallium-68 (68Ga). Building on our efforts to produce 68Ga in a liquid target on a GE PETtrace, the goal of this work is to modify the current GE Gallium Chloride cassette using the FASTLab 2 synthesis module to produce [68Ga]GaCl3 equivalent to a 1.85 GBq generator and demonstrate compatibility with FDA-approved kits for production of 68Ga-labeled radiopharmaceuticals. Methods68Ga was produced in a liquid target via the 68Zn(p,n)68Ga reaction. 68Ga was loaded onto various sizes of ZR resins (ZR Load, 0.3 mL, 1 mL, or 2 mL). The loading efficiency was determined using a dose calibrator. After washing with HNO3, 1.75 M HCl was used to elute the ZR Load resin through various sizes of a second ZR resin (ZR CG, 0 mL, 2 mL, 4 mL). Using 0.5 mL fractions, the elution profile was determined. Compatibility of the [68Ga]GaCl3 with NetSpot and Illuccix kits was investigated. Radiochemical purity (RCP) and 4 h stability were determined using radioTLC and radioHPLC. Using a modified [68Ga]GaCl3 cassette and new FASTLab program, 6 validation preparations were conducted using NetSpot and Illuccix kits for which RCP, stability, sterility and suitability were determined. Dual irradiation of 2 liquid targets was also performed, which was used to simultaneously prepare 1 NetSpot and 2 Illuccix kits by diluting the required activity with 0.1 M HCl. ResultsThe commercially available GE Cassette gave low RCP using commercial FDA kits. To optimize this, the loading efficiency onto ZR Load and the ratio of ZR resin used to load the initial activity and subsequent elution were explored. When using a 2:4 ratio of ZR Load to ZR CG, 97.89 % RCP was observed when a 3.8 mL [68Ga]GaCl3 solution was used. For Dotatate validation, 0.55 mL of buffer was added to 4.2 mL of [68Ga]GaCl3 which gave 1.35 GBq of formulated product. For Illuccix validation, [68Ga]GaCl3 was added to 2.5 mL of buffer which gave 1.52 GBq of [68Ga]Ga-PSMA-11. Formulated products passed package insert quality control (QC) requirements. When dual target irradiations were performed, 2.84 GBq was delivered to an external vial and used to label 1 NetSpot and 2 Illuccix kits simultaneously, and each kit also met or exceeded established QC criteria. ConclusionMethods are reported for using cyclotron-produced 68Ga from a liquid target in conjunction with FDA-approved NetSpot and Illucix kits. By employing a 2 mL ZR Load resin with a 4 mL ZR CG resin, adequate resolution between residual 68Zn and desired 68Ga was achieved. By modifying the FASTLab procedure to retain the final 2.5 mL of eluate from the ZR CG resin, [68Ga]GaCl3 equivalent to a new 1.85 GBq generator was obtained. This was suitable for labeling NetSpot and Illucix kits, resulting in high incorporation of 68Ga (RCP >95 %), which has not previously been demonstrated. Delivering [68Ga]GaCl3 into an external vial and diluting with 0.1 M HCl makes it possible to prepare multiple kits simultaneously. These new procedures should facilitate use of cyclotron-produced [68Ga]GaCl3 for clinical production going.