Contralateral Hypertrophy Post Yttrium-90 Transarterial Radioembolization in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombus.

Objectives Contralateral hypertrophy of non-irradiated liver following Yttrium-90 (90Y) transarterial radioembolization (TARE) is increasingly recognized as an option to facilitate curative surgical resection in patients that would otherwise not be surgical candidates due to a small future liver remnant (FLR). This study aimed to investigate the correlation between patient features and liver hypertrophy and identify potential predictors for liver growth in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing TARE. Methodology Twenty-three patients with HCC and PVTT were included. Contralateral liver hypertrophy was assessed at six months posttreatment based on CT or MRI imaging. Thirteen patient features were selected for statistical and prediction analysis. Univariate Spearman correlation and analysis of variance (ANOVA) tests were performed. Subsequently, four feature-selection methods based on multivariate analysis were used to improve model generalization performance. The selected features were applied to train linear regression models, with fivefold cross-validation to assess the performance of the predicted models. Results The ratio of disease-free target liver volume to spared liver volume and total liver volume showed the highest correlations with contralateral hypertrophy (P-values = 0.03 and 0.05, respectively). In three out of four feature-selection methods, the feature of disease-free target liver volume to total liver volume ratio was selected, having positive correlations with the outcome and suggesting that more hypertrophy may be expected when more volume of disease-free liver is irradiated. Conclusions Contralateral hypertrophy post-90Y TARE can be an option for facilitating surgical resection in patients with otherwise small FLR.

Deep transformer-based personalized dosimetry from SPECT/CT images: a hybrid approach for [177Lu]Lu-DOTATATE radiopharmaceutical therapy.

PURPOSE: Accurate dosimetry is critical for ensuring the safety and efficacy of radiopharmaceutical therapies. In current clinical dosimetry practice, MIRD formalisms are widely employed. However, with the rapid advancement of deep learning (DL) algorithms, there has been an increasing interest in leveraging the calculation speed and automation capabilities for different tasks. We aimed to develop a hybrid transformer-based deep learning (DL) model that incorporates a multiple voxel S-value (MSV) approach for voxel-level dosimetry in [177Lu]Lu-DOTATATE therapy. The goal was to enhance the performance of the model to achieve accuracy levels closely aligned with Monte Carlo (MC) simulations, considered as the standard of reference. We extended our analysis to include MIRD formalisms (SSV and MSV), thereby conducting a comprehensive dosimetry study. METHODS: We used a dataset consisting of 22 patients undergoing up to 4 cycles of [177Lu]Lu-DOTATATE therapy. MC simulations were used to generate reference absorbed dose maps. In addition, MIRD formalism approaches, namely, single S-value (SSV) and MSV techniques, were performed. A UNEt TRansformer (UNETR) DL architecture was trained using five-fold cross-validation to generate MC-based dose maps. Co-registered CT images were fed into the network as input, whereas the difference between MC and MSV (MC-MSV) was set as output. DL results are then integrated to MSV to revive the MC dose maps. Finally, the dose maps generated by MSV, SSV, and DL were quantitatively compared to the MC reference at both voxel level and organ level (organs at risk and lesions). RESULTS: The DL approach showed slightly better performance (voxel relative absolute error (RAE) = 5.28 ± 1.32) compared to MSV (voxel RAE = 5.54 ± 1.4) and outperformed SSV (voxel RAE = 7.8 ± 3.02). Gamma analysis pass rates were 99.0 ± 1.2%, 98.8 ± 1.3%, and 98.7 ± 1.52% for DL, MSV, and SSV approaches, respectively. The computational time for MC was the highest (~2 days for a single-bed SPECT study) compared to MSV, SSV, and DL, whereas the DL-based approach outperformed the other approaches in terms of time efficiency (3 s for a single-bed SPECT). Organ-wise analysis showed absolute percent errors of 1.44 ± 3.05%, 1.18 ± 2.65%, and 1.15 ± 2.5% for SSV, MSV, and DL approaches, respectively, in lesion-absorbed doses. CONCLUSION: A hybrid transformer-based deep learning model was developed for fast and accurate dose map generation, outperforming the MIRD approaches, specifically in heterogenous regions. The model achieved accuracy close to MC gold standard and has potential for clinical implementation for use on large-scale datasets.

177Lu SPECT imaging in the presence of90Y: does90Y degrade image quantification? a simulation study.

This work aims to investigate the accuracy of quantitative SPECT imaging of177Lu in the presence of90Y, which occurs in dual-isotope radiopharmaceutical therapy (RPT) involving both isotopes. We used the GATE Monte Carlo simulation toolkit to conduct a phantom study, simulating spheres filled with177Lu and90Y placed in a cylindrical water phantom that was also filled with activity of both radionuclides. We simulated multiple phantom configurations and activity combinations by varying the location of the spheres, the concentrations of177Lu and90Y in the spheres, and the amount of background activity. We investigated two different scatter window widths to be used with triple energy window (TEW) scatter correction. We also created multiple realizations of each configuration to improve our assessment, leading to a total of 540 simulations. Each configuration was imaged using a simulated Siemens SPECT camera. The projections were reconstructed using the standard 3D OSEM algorithm, and errors associated with177Lu activity quantification and contrast-to-noise ratios (CNRs) were determined. In all configurations, the quantification error was within ± 6% of the no-90Y case, and we found that quantitative accuracy may slightly improve when90Y is present because of reduction of errors associated with TEW scatter correction. The CNRs were not significantly impacted by the presence of90Y, but they were increased when a wider scatter window width was used for TEW scatter correction. The width of the scatter windows made a small but statistically significant difference of 1%-2% on the recovered177Lu activity. Based on these results, we can conclude that activity quantification of177Lu and lesion detectability is not degraded by the presence of90Y.

Feasibility of Single-Time-Point Dosimetry for Radiopharmaceutical Therapies.

Because of challenges in performing routine personalized dosimetry in radiopharmaceutical therapies, interest in single-time-point (STP) dosimetry, particularly using only a single SPECT scan, is on the rise. Meanwhile, there are questions about the reliability of STP dosimetry, with limited independent validations. In the present work, we analyzed 2 STP dosimetry methods and evaluated dose errors for several radiopharmaceuticals based on effective half-life distributions. Methods: We first challenged the common assumption that radiopharmaceutical effective half-lives across the population are gaussian-distributed (i.e., follow a normal distribution). Then, dose accuracy was estimated using 2 STP dosimetry methods for a wide range of potential post injection (p.i.) scan time points for different radiopharmaceuticals applied to neuroendocrine tumors and prostate cancer. The accuracy and limitations of each of the STP methods were discussed. Results: A lognormal distribution was more appropriate for capturing effective half-life distributions. The STP framework was promising for dosimetry of 177Lu-DOTATATE and for kidney dosimetry of different radiopharmaceuticals (errors < 30%). Meanwhile, for some radiopharmaceuticals, STP accuracy was compromised (e.g., in bone marrow and tumors for 177-labeled prostate-specific membrane antigen [PSMA])). The optimal SPECT scanning time for 177Lu-DOTATATE was approximately 72 h p.i., whereas 48 h p.i. was better for 177Lu-PSMA. Conclusion: Simplified STP dosimetry methods may compromise the accuracy of dose estimates, with some exceptions, such as for 177Lu-DOTATATE and for kidney dosimetry in different radiopharmaceuticals. Simplified personalized dosimetry in the clinic continues to be challenging. On the basis of our results, we make suggestions and recommendations for improved personalized dosimetry using simplified imaging schemes.

Impact of image reconstruction method on dose distributions derived from 90Y PET images: phantom and liver radioembolization patient studies.

PET images acquired after liver 90Y radioembolization therapies are typically very noisy, which significantly challenges both visualization and quantification of activity distributions. To improve their noise characteristics, regularized iterative reconstruction algorithms such as block sequential regularized expectation maximization (Q.Clear for GE Healthcare, USA) have been proposed. In this study, we aimed to investigate the effects which different reconstruction algorithms may have on patient images, with reconstruction parameters initially narrowed down using phantom studies. Moreover, we evaluated the impact of these reconstruction methods on voxel-based dose distribution in phantom and patient studies (lesions and healthy livers). The International Electrotechnical Commission (IEC)/NEMA phantom, containing six spheres, was filled with 90Y and imaged using a GE Discovery 690 PET/CT scanner with time-of-flight enabled. The images were reconstructed using Q.Clear (with ß parameter ranging from 0 to 8000) and ordered subsets expectation maximization. The image quality and quantification accuracy were evaluated by computing the hot ([Formula: see text]) and cold ([Formula: see text]) contrast recovery coefficients, background variability (BV) and activity bias. Next, dose distributions and dose volume histograms were generated using MIM® software's SurePlan LiverY90 toolbox. Subsequently, parameters optimized in these phantom studies were applied to five patient datasets. Dose parameters, such as Dmax, Dmean, D70, and V100Gy, were estimated, and their variability for different reconstruction methods was investigated. Based on phantom studies, the ß parameter values optimized for image quality and quantification accuracy were 2500 and 300, respectively. When all investigated reconstructions were applied to patient studies, Dmean, D50, D70, and V100Gy showed coefficients of variation below 8%; whereas the variability of Dmax was up to 30% for both phantom and patient images. Although ß = 300-1000 would provide accurate activity quantification for a region of interest, when considering activity/dose voxelized distribution, higher ß value (e.g. 4000-5000) would provide the greatest accuracy for dose distributions. In this 90Y radioembolization PET/CT study, the ß parameter in regularized iterative (Q.Clear) reconstruction was investigated for image quality, accurate quantification and dose distributions based on phantom experiments and then applied to patient studies. Our results indicate that more accurate dose distribution can be achieved from smoother PET images, reconstructed with larger ß values than those yielding the best activity quantifications but noisy images. Most importantly, these results suggest that quantitative measures, which are commonly used in clinics, such as SUVmax or SUVpeak( equivalent of Dmax), should not be employed for 90Y PET images, since their values would highly depend on the image reconstruction.

Personalized kidney dosimetry in 177Lu-octreotate treatment of neuroendocrine tumours: a comparison of kidney dosimetry estimates based on a whole organ and small volume segmentations.

Peptide receptor radionuclide therapy (PRRT) with 177Lu- radiolabeled octreotate is an effective treatment method for inoperable neuroendocrine tumours (NETs). There is growing evidence that estimates of the organ-at-risks (OARs) doses are necessary for the optimization of personalized PRRT (P-PRRT). Dosimetry, however, requires a complicated and time-consuming procedure, which hinders its implementation in the clinic. The aim of this study is to develop a practical and automatic technique to simplify personalized dosimetry of kidney, the major OAR in 177Lu P-PRRT. The data from 30 NETs patients undergoing 44 personalized 177Lu-DOTA-TATE therapy cycles were analyzed. To determine the biokinetics of the radiopharmaceutical in the kidneys, for each patient three SPECT/CT scans were acquired, at about 4 h, 24 h and 70 h after injection. The kidneys doses were evaluated using three different approaches: (1) a traditional approach based on whole kidney (WK) segmentation; (2) a small volume (SV) manual approach (M-SV) with observer-defined SV location; and (3) a software based SV-approach that automatically defines SV location (A-SV). Four different methods of automatic SV location selections were investigated. The SV kidney doses estimated using M-SV and A-SV approaches was evaluated and the accuracy of these two approaches were compared to the WK dosimetry. The kidney bio-kinetics, in terms of effective half-lives, obtained from both of the A-SV and M-SV approaches agreed to within 10% with those obtained from the WK segmentation. The average ratios of SV doses to WK doses were mostly about 1.8 ± 0.2 for both A-SV and M-SV approaches. The linear correlation coefficients between SV doses (both A-SV and M-SV) and WK doses were up to 0.9 with p  < 0.001. The differences between A-SV and M-SV were minor. By comparing different methods of SV location selections, independently selecting SV in images from each of the acquisitions was proved the most appropriate and accurate approach. An automatic, observer-independent method for selecting the location of the small volume in kidneys was developed. The accuracy of this dose estimation approach has been demonstrated by comparing it with the manual SV dosimetry, as well as the WK dosimetry. The proposed automatic approach can potentially be considered as a practical and simple method for dose estimation in the future clinical studies.

Accuracy of kidney dosimetry performed using simplified time activity curve modelling methods: a 177Lu-DOTATATE patient study.

177Lu-DOTATATE therapy has been shown to produce encouraging results in treatment of neuroendocrine tumours (NETs). Unfortunately, since dosimetry for radionuclide therapy is considered to be challenging, typically similar amount of radiopharmaceutical is administered to every patient. There is growing evidence that the efficacy of this therapy can be significantly improved by employing personalized protocols, based on the organ-at-risk dosimetry. The aim of this study is to propose a practical and accurate dosimetry protocol based on the simplified acquisition schedules. Data from fifty-three therapy cycles in thirty-nine NET patients were analyzed. Three SPECT/CT scans, acquired at 4 h (D0), 23 h (D1) and 70 h (D3) after injection, were performed. The kidney volume was determined using CT and the activity was determined from quantitative SPECT using an iterative thresholding method. For each dataset, four methods were used to model the time-activity-curves (TAC): M1-two trapezoid segments (0 to D0 and D0 to D1), followed by monoexponential fit to D1 + D3 data; M2-monoexponential fit to D0 + D1 + D3 data; M3 and M4-monoexponential fit to D0 + D3 and D1 + D3 data, respectively. Additionally, kidney doses obtained from single time point method using a monoexponential curve with the population mean effective half-life, normalized to activities at D0 or D1 or D3 points, were calculated. The accuracy of simplified dosimetry methods was assessed as the percentage difference relative to doses calculated from M1. The major contribution to the absorbed dose estimate comes from the area under the late time portion of the TAC (D1 to infinity). Therefore, information from the late scan (D3) is crucial for the determination of kidney absorbed doses. Single time point method using monoexponential TAC, with the population mean effective half-life normalized to the late data point (48-72 h for kidneys) produces <10% deviation in the absorbed dose estimation, thus is recommended for clinical use.

Determination of gamma camera calibration factors for quantitation of therapeutic radioisotopes.

BACKGROUND: Camera calibration, which translates reconstructed count map into absolute activity map, is a prerequisite procedure for quantitative SPECT imaging. Both planar and tomographic scans using different phantom geometries have been proposed for the determination of the camera calibration factor (CF). However, there is no consensus on which approach is the best. The aim of this study is to evaluate all these calibration methods, compare their performance, and propose a practical and accurate calibration method for SPECT quantitation of therapeutic radioisotopes. Twenty-one phantom experiments (Siemens Symbia SPECT/CT) and 12 Monte Carlo simulations (GATE v6.1) using three therapy isotopes (131I, 177Lu, and 188Re) have been performed. The following phantom geometries were used: (1) planar scans of point source in air (PS), (2) tomographic scans of insert(s) filled with activity placed in non-radioactive water (HS + CB), (3) tomographic scans of hot insert(s) in radioactive water (HS + WB), and (4) tomographic scans of cylinders uniformly filled with activity (HC). Tomographic data were reconstructed using OSEM with CT-based attenuation correction and triple energy window (TEW) scatter correction, and CF was determined using total counts in the reconstructed image, while for planar scans, the photopeak counts, corrected for scatter and background with TEW, were used. Additionally, for simulated data, CF obtained from primary photons only was analyzed. RESULTS: For phantom experiments, CF obtained from PS and HS + WB agreed to within 6% (below 3% if experiments performed on the same day are considered). However, CF from HS + CB exceeded those from PS by 4-12%. Similar trend was found in simulation studies. Analysis of CFs from primary photons helped us to understand this discrepancy. It was due to underestimation of scatter by the TEW method, further enhanced by attenuation correction. This effect becomes less important when the source is distributed over the entire phantom volume (HS + WB and HC). CONCLUSIONS: Camera CF could be determined using planar scans of a point source, provided that the scatter and background contributions are removed, for example using the clinically available TEW method. This approach is simple and yet provides CF with sufficient accuracy (~ 5%) to be used in clinics for radiotracer quantification.

Segmentation-free direct tumor volume and metabolic activity estimation from PET scans.

Tumor volume and metabolic activity are two robust imaging biomarkers for predicting early therapy response in F-fluorodeoxyglucose (FDG) positron emission tomography (PET), which is a modality to image the distribution of radiotracers and thereby observe functional processes in the body. To date, estimation of these two biomarkers requires a lesion segmentation step. While the segmentation methods requiring extensive user interaction have obvious limitations in terms of time and reproducibility, automatically estimating activity from segmentation, which involves integrating intensity values over the volume is also suboptimal, since PET is an inherently noisy modality. Although many semi-automatic segmentation based methods have been developed, in this paper, we introduce a method which completely eliminates the segmentation step and directly estimates the volume and activity of the lesions. We trained two parallel ensemble models using locally extracted 3D patches from phantom images to estimate the activity and volume, which are derivatives of other important quantification metrics such as standardized uptake value (SUV) and total lesion glycolysis (TLG). For validation, we used 54 clinical images from the QIN Head and Neck collection on The Cancer Imaging Archive, as well as a set of 55 PET scans of the Elliptical Lung-Spine Body Phantom™with different levels of noise, four different reconstruction methods, and three different background activities, namely; air, water, and hot background. In the validation on phantom images, we achieved relative absolute error (RAE) of 5.11 % ±3.5% and 5.7 % ±5.25% for volume and activity estimation, respectively, which represents improvements of over 20% and 6% respectively, compared with the best competing methods. From the validation performed using clinical images, we found that the proposed method is capable of obtaining almost the same level of agreement with a group of trained experts, as a single trained expert is, indicating that the method has the potential to be a useful tool in clinical practice.

Patient-specific dosimetry of 99mTc-HYNIC-Tyr3-Octreotide in children.

BACKGROUND: Technetium-99m-hydrazinonicotinamide-Tyr3-octreotide (99mTc-HYNIC-TOC) is recognized as a promising radiopharmaceutical for diagnosing neuroendocrine tumors (NETs). However, 99mTc-HYNIC-TOC dosimetry has been investigated only for adults. As pediatric radionuclide therapies become increasingly common, similar dosimetric studies for children are urgently needed. The aim of this study is to report personalized image-based biodistributions and dosimetry evaluations for children studies performed using 99mTc-HYNIC-TOC and to compare them with those from adult subjects. Eleven children/teenage patients with suspected or diagnosed NETs were enrolled. Patient imaging included a series of 2-3 whole-body planar scans and SPECT/CT performed over 2-24 h after the 99mTc-HYNIC-TOC injections. The time-integrated activity coefficients (TIACs) were obtained from the hybrid planar/SPECT technique. Patient-specific doses were calculated using both the voxel-level and the organ-level approaches. Estimated children doses were compared with adults' dosimetry. RESULTS: Pathologic uptake was observed in five patients. TIACs for normal organs with significant uptakes, i.e., kidneys, spleen, and liver, were similar to adults' TIACs. Using the voxel-level approach, the average organ doses for children were 0.024 ± 0.009, 0.032 ± 0.017, and 0.017 ± 0.007 mGy/MBq for the kidneys, spleen, and liver, respectively, which were 30% larger than adults' doses. Similar values were obtained from the organ-level dosimetry when using OLINDA with adapted organ masses. Tumor doses were 0.010-0.024 mGy/MBq. However, cross-organ contributions were much larger in children than in adults, comprising about 15-40% of the total organ/tumor doses. No statistical differences were found between mean doses and dose distributions in patients with and without pathologic uptakes. CONCLUSION: Although the children TIACs were similar to those in adults, their doses were about 30% higher. No significant correlation was found between the children's doses and their ages. However, substantial inter-patient variability in radiotracer uptake, indicating disparity in expression of somatostatin receptor between different patients, emphasizes the importance and necessity of patient-specific dosimetry for clinical studies.

Production of Y-86 and other radiometals for research purposes using a solution target system.

INTRODUCTION: Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF. Details about the production, purification and quality control of (89)Zr, (68)Ga and for the first time (86)Y are discussed. METHODS: Aqueous solutions containing 1.35-1.65 g/mL of natural-abundance zinc nitrate, yttrium nitrate, and strontium nitrate were irradiated on a 13 MeV cyclotron using a standard liquid target. Different target body and foil materials were investigated for corrosion. Production yields were calculated using theoretical cross-sections from the EMPIRE code and compared with experimental results. The radioisotopes were extracted from irradiated target material using solid phase extraction methods adapted from previously reported methods, and used for radiolabelling experiments. RESULTS: We demonstrated production quantities that are sufficient for chemical and biological studies for three separate radiometals, (89)Zr (Asat = 360 MBq/µA and yield = 3.17 MBq/µA), (86)Y (Asat = 31 MBq/µA and yield = 1.44 MBq/µA), and (68)Ga (Asat = 141 MBq/µA and yield = 64 MBq/µA) from one hour long irradiations on a typical medical cyclotron. (68)Ga yields were sufficient for potential clinical applications. In order to avoid corrosion of the target body and target foil, nitrate solutions were chosen as well as niobium as target-body material. An automatic loading system enabled up to three production runs per day. The separation efficiency ranged from 82 to 99%. Subsequently, (68)Ga and (86)Y were successfully used to radiolabel DOTA-based chelators while deferoxamine was used to coordinate (89)Zr.

Cross-linked polyethylene glycol beads to separate 99mTc-pertechnetate from low-specific-activity molybdenum.

UNLABELLED: We report a kit-based approach for the purification of sodium pertechnetate ((99m)TcO4 (-)) from solutions with high MoO4 (2-) content. METHODS: Cross-linked polyethylene glycol resins (ChemMatrix) were used to separate (99m)Tc and molybdenum in 4N NaOH. The resins were loaded at various flow rates and eluted with water to release (99m)Tc. The (99m)Tc solution was passed through a cation exchange resin and an alumina cartridge, followed by saline elution. This process was tested with cyclotron-produced (99m)Tc using an automated system and disposable kits. RESULTS: Optimal results were obtained by loading 500 mg of resin at flow rates of up to 3.1 mL/min, with quantitative extraction of (99m)Tc from the molybdate solution and complete release of (99m)Tc after elution with water. The automated system was highly efficient at isolating Na(99m)TcO4 within minutes, with a recovery rate of 92.7% ± 1.1% (mean ± SD) using cyclotron-produced (99m)Tc. CONCLUSION: ChemMatrix resins were highly effective at separating (99m)TcO4 (-) from molybdate solutions.

Implementation of Multi-Curie Production of (99m)Tc by Conventional Medical Cyclotrons.

UNLABELLED: (99m)Tc is currently produced by an aging fleet of nuclear reactors, which require enriched uranium and generate nuclear waste. We report the development of a comprehensive solution to produce (99m)Tc in sufficient quantities to supply a large urban area using a single medical cyclotron. METHODS: A new target system was designed for (99m)Tc production. Target plates made of tantalum were coated with a layer of (100)Mo by electrophoretic deposition followed by high-temperature sintering. The targets were irradiated with 18-MeV protons for up to 6 h, using a medical cyclotron. The targets were automatically retrieved and dissolved in 30% H2O2. (99m)Tc was purified by solid-phase extraction or biphasic exchange chromatography. RESULTS: Between 1.04 and 1.5 g of (100)Mo were deposited on the tantalum plates. After high-temperature sintering, the (100)Mo formed a hard, adherent layer that bonded well with the backing surface. The targets were irradiated for 1-6.9 h at 20-240 µA of proton beam current, producing up to 348 GBq (9.4 Ci) of (99m)Tc. The resulting pertechnetate passed all standard quality control procedures and could be used to reconstitute typical anionic, cationic, and neutral technetium radiopharmaceutical kits. CONCLUSION: The direct production of (99m)Tc via proton bombardment of (100)Mo can be practically achieved in high yields using conventional medical cyclotrons. With some modifications of existing cyclotron infrastructure, this approach can be used to implement a decentralized medical isotope production model. This method eliminates the need for enriched uranium and the radioactive waste associated with the processing of uranium targets.

(44g)Sc production using a water target on a 13MeV cyclotron.

INTRODUCTION: Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of 44Sc (t1/2=3.97 h, Eavg,ß⁺=1.47MeV, branching ratio=94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations. METHODS: Solutions containing a high concentration (1.44-1.55g/mL) of natural-abundance calcium nitrate tetrahydrate (Ca(NO3)2·4 H2O) were irradiated on a 13MeV proton-beam cyclotron using a standard liquid target. (44g)Sc was produced via the 44Ca(p,n)(44g)Sc reaction. RESULTS: (44g)Sc was produced for the first time in a solution target with yields sufficient for early radiochemical studies. Saturation yields of up to 4.6 ± 0.3 MBq/µA were achieved using 7.6 ± 0.3 µA proton beams for 60.0 ± 0.2 minutes (number of runs n=3). Experimental data and calculation results are in fair agreement. Scandium was isolated from the target mixture via solid-phase extraction with 88 ± 6% (n=5) efficiency and successfully used for radiolabelling experiments. The demonstration of the production of 44Sc in a liquid target greatly improves its availability for tracer development.