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Theranostic isotope pairs have gained recent clinical interest as they can be labeled to the same tracer and applied for diagnostic and therapeutic purposes. The goals of this study were to A) investigate cyclotron production of clinically relevant 133La activities using natural and isotopically enriched barium target material, B) compare fundamental positron emission tomography (PET) phantom imaging characteristics of 133La with common PET radionuclides, and C) demonstrate in vivo preclinical PET tumor imaging using 133La-PSMA-I&T. Methods:133La was produced on a 24 MeV cyclotron using an aluminum-indium sealed target with 150-200 mg of isotopically enriched 135BaCO3, natBaCO3, and natBa metal. A NEPTIS Mosaic-LC performed Ba/La separation. DOTA, PSMA-I&T, and macropa were radiolabeled with 133La. Derenzo and National Electrical Manufacturers Association (NEMA) phantom imaging was performed with 133La, 132La, and 89Zr and compared with 18F, 68Ga, 44Sc, and 64Cu. In vivo preclinical imaging was performed with 133La-PSMA-I&T in LNCaP tumor-bearing mice. Results: Proton irradiations for 100 µA·min at 23.3 MeV yielded 214 ± 7 MBq 133La and 28 ± 1 MBq 135La using 135BaCO3, 59 ± 2 MBq 133La and 35 ± 1 MBq 135La using natBaCO3 and 81 ± 3 MBq 133La and 48 ± 1 MBq 135La using natBa metal. At 11.9 MeV, 135La yields were: 81 ± 2 MBq, 6.8 ± 0.4 MBq, and 9.9 ± 0.5 MBq for 135BaCO3, natBaCO3, and natBa metal. BaCO3 target material recovery was 95.4 ± 1.7%. NEMA and Derenzo phantom imaging demonstrated 133La PET spatial resolution, and scanner recovery coefficient were superior compared to 68Ga, 132La, and comparable to 89Zr. The apparent molar activity was 130 ± 15 GBq/μmol with DOTA, 73 ± 18 GBq/μmol with PSMA-I&T, and 206 ± 31 GBq/μmol with macropa. Preclinical PET imaging with 133La-PSMA-I&T provided high-resolution tumor visualization with a SUV60min of 0.97 ± 0.17. Conclusion: With high-yield 133La cyclotron production, recovery of BaCO3 target material, and superior fundamental imaging characteristics compared to 68Ga and 132La, 133La represents a promising radiometal candidate to provide high-resolution PET imaging as a PET/alpha therapy theranostic pair with 225Ac, or a PET/Auger electron therapy theranostic pair with 135La.

Radiolabeled peptides play a central role in nuclear medicine as radiotheranostics for targeted imaging and therapy of cancer. We have recently proposed the use of metabolically stabilized GRPR antagonist BBN2 for radiolabeling withDOTA-Ava-BBN2 was radiolabeled with radiometalsRadiopeptides [Comparison ofThe favorable PET imaging performance of [

Almandine garnet is used commonly in abrasive blasting processes to prepare metallic surfaces for painting. However, there is evidence that the process leads to significant amounts of abrasive embedded in the “cleaned” surface, and hence the surface chemistry of garnet will affect the binding of any coatings subsequently applied. In addition, in marine environments seawater aerosol droplets are expected to impact the exposed surface prior to coating application, depositing both water and dissolved inorganic ions. In this work, we provide indepth analysis of the chemistry of the almandine garnet surface using angle-resolved X-ray photoelectron spectroscopy (XPS) and note a correlation for several elemental oxides between literature values of the binding energy of the surface oxygen 1s XPS peak and the basicity of the hydroxyl group that forms on the surface. We also consider the adsorption to almandine garnet powder of seawater-relevant inorganic ions (sodium, magnesium, and calcium): Binding constants have been determined using titration measurements, solution-depletion isotherms, and numerical modeling, with calcium observed to bind more strongly than magnesium. The relevance of Langmuir-type fits to constant-pH adsorption isotherms is discussed. By contrast, sodium either binds very weakly or is effectively inert toward the garnet surface under the experimental conditions. The complex adsorption behavior observed emphasizes the necessity of using multiple techniques to characterize mineral surfaces.

Purpose The decay characteristics of radionuclides in PET studies can impact image reconstruction. 44gSc has been the topic of recent research due to potential theranostic applications and is a promising radiometal for PET imaging. In this study, the reconstructed images from phantom measurements with scandium in a small-animal PET scanner are compared with 18F and two prominent radiometals: 64Cu and 68Ga Methods Three phantoms filled with 18F, 64C, 68Ga, and 44gSc were imaged in the Siemens Inveon PET scanner. The NEMA image quality phantom was used to determine the recovery coefficients (RCs), spill-over ratios (SORs), and noise (%SD) under typical pre-clinical imaging conditions. Image contrast was determined using a Derenzo phantom, while the coincidence characteristics were investigated using an NEC phantom. Three reconstruction algorithms were used, namely filtered back projection (FBP), ordered subset expectation maximization (OSEM), and maximum a-posteriori (MAP). Results Image quality parameters were measured for 18F, 64Cu, 68Ga, and 44gSc respectively; using FBP, the %SD are 5.65, 5.88, 7.28, and 7.70; the RCs for the 5-mm rod are 0.849, 1.01, 0.615, and 0.825; the SORs in water are 0.0473, 0.0595, 0.141, 0.0923; and the SORs in air are 0.0589, 0.0484, 0.0525, and 0.0509. The contrast measured in the 2.5-mm rods are 0.674, 0.637, 0.196, and 0.347. The NEC rate with 44gSc increased at a slower rate than 18F and 68Ga as a function of activity in the field of view. Conclusion 44gSc demonstrates intermediate behavior relative to 18F and 68Ga with regard to RC and contrast measurements. It is a promising radionuclide for preclinical imaging.

Bis(2-ethylhexyl) phosphate (BEHP) was exposed to carbon steel surfaces from dry and water-saturated dodecane. The resulting changes to the surfaces were characterised using spectroscopic techniques (energy dispersive X-ray (EDX), X-ray photoelectron (XPS), and far-infrared reflection absorption (RAIRS) spectroscopies) and polarised neutron reflectometry (PNR). Although there was no observable affinity of BEHP to the steel surface in dry solvent, a layer of rough iron (III) phosphate formed in water-saturated dodecane. The phosphate-reacted steel surface showed some resistance to corrosion by seawater, suggesting the formation of a cohesive barrier against corrosive species. The results support the use of BEHP as an anti-corrosion additive and a viable phosphating agent for steel surfaces.

Purpose: To present and evaluate an ion chamber-based method for the cross-calibration between sites of activity measurements of unsealed radionuclides. Notably, the method allows direct comparison of short lived (i.e., clinically used) radioisotopes and the cross-calibration of radionuclide activity meters (also known as “dose calibrators”). Methods: A portable ion chamber has been designed which is easily shipped between sites, e.g., between a standards laboratory and a nuclear medicine department. The cylindrical chamber accommodates a syringe filled with unsealed radionuclide. Low background and staff shielding are achieved by designing the ion chamber small enough to fit into the well of a dose calibrator. The chamber's sensitivity for the clinically important unsealed radioisotopes 99mTc, 131I, and 18F was measured and compared to Monte Carlo calculations. The influence of syringe fill volume, positioning, and construction (wall diameter, length) was also investigated using Monte Carlo simulations. The chamber's linearity was measured over 5.5 orders of magnitude and its constancy tested over a period of >14.5 months. An overall uncertainty budget is presented. Results: Measured chamber sensitivity was 12.1 pA/100 MBq, 12.5 pA/100 MBq and 29.4 pA/100 MBq for 131I, 99mTc, and 18F, respectively. The uncertainty budget for the ion chamber alone yields an overall uncertainty of less than 1%, with the greatest contribution arising from constancy and linearity (0.5% each). Strategies to further reduce uncertainties are discussed. Conclusions: The investigation presented in this paper confirms the feasibility of the concept introduced here. To optimize its practical implementation, the concept would benefit from computerization for the purpose of data acquisition, evaluation, processing, and storage of measured values.

There is a wide diversity of production methods for radionuclides. With these, intensive calculations are often required to characterize the different radionuclide production strategies and to determine optimal irradiation parameters. These calculations are essential for predicting the yield and radionuclidic purity of the resulting product. In this work, a graphical user interface (GUI) has been built in Matlab® to facilitate these production calculations and compare production methods. The user is able to import cross-sections, define target compositions and outline irradiation conditions for calculating yields. This GUI facilitates the process of varying irradiation parameters and allows the user to determine the yield of radionuclides as a function of energy and time.

To estimate the total dosimetric uncertainty at the tumor apex for ocular brachytherapy treatments delivered using 16 mm Collaborative Ocular Melanoma Study (COMS) and Super9 plaques loaded with (125)I seeds in order to determine the size of the apex margin that would be required to ensure adequate dosimetric coverage of the tumor.The total dosimetric uncertainty was assessed for three reference tumor heights: 3, 5, and 10 mm, using the Guide to the expression of Uncertainty in Measurement/National Institute of Standards and Technology approach. Uncertainties pertaining to seed construction, source strength, plaque assembly, treatment planning calculations, tumor height measurement, plaque placement, and plaque tilt for a simple dome-shaped tumor were investigated and quantified to estimate the total dosimetric uncertainty at the tumor apex. Uncertainties in seed construction were determined using EBT3 Gafchromic film measurements around single seeds, plaque assembly uncertainties were determined using high resolution microCT scanning of loaded plaques to measure seed positions in the plaques, and all other uncertainties were determined from the previously published studies and recommended values. All dose calculations were performed using plaque simulator v5.7.6 ophthalmic treatment planning system with the inclusion of plaque heterogeneity corrections.The total dosimetric uncertainties at 3, 5, and 10 mm tumor heights for the 16 mm COMS plaque were 17.3%, 16.1%, and 14.2%, respectively, and for the Super9 plaque were 18.2%, 14.4%, and 13.1%, respectively (all values with coverage factor k = 2). The apex margins at 3, 5, and 10 mm tumor heights required to adequately account for these uncertainties were 1.3, 1.3, and 1.4 mm, respectively, for the 16 mm COMS plaque, and 1.8, 1.4, and 1.2 mm, respectively, for the Super9 plaque. These uncertainties and associated margins are dependent on the dose gradient at the given prescription depth, thus resulting in the changing uncertainties and margins with depth.The margins determined in this work can be used as a guide for determining an appropriate apex margin for a given treatment, which can be chosen based on the tumor height. The required margin may need to be increased for more complex scenarios (mushroom shaped tumors, tumors close to the optic nerve, oblique muscle related tilt, etc.) than the simple dome-shaped tumor examined and should be chosen on a case-by-case basis. The sources of uncertainty contributing most significantly to the total dosimetric uncertainty are seed placement within the plaques, treatment planning calculations, tumor height measurement, and plaque tilt. This work presents an uncertainty-based, rational approach to estimating an appropriate apex margin.

Noise levels observed in positron emission tomography (PET) images complicate their geometric interpretation. Post-processing techniques aimed at noise reduction may be employed to overcome this problem. The detailed characteristics of the noise affecting PET images are, however, often not well known. Typically, it is assumed that overall the noise may be characterized as Gaussian. Other PET-imaging-related studies have been specifically aimed at the reduction of noise represented by a Poisson or mixed Poisson + Gaussian model. The effectiveness of any approach to noise reduction greatly depends on a proper quantification of the characteristics of the noise present. This work examines the statistical properties of noise in PET images acquired with a GEMINI PET/CT scanner. Noise measurements have been performed with a cylindrical phantom injected with (11)C and well mixed to provide a uniform activity distribution. Images were acquired using standard clinical protocols and reconstructed with filtered-backprojection (FBP) and row-action maximum likelihood algorithm (RAMLA). Statistical properties of the acquired data were evaluated and compared to five noise models (Poisson, normal, negative binomial, log-normal, and gamma). Histograms of the experimental data were used to calculate cumulative distribution functions and produce maximum likelihood estimates for the parameters of the model distributions. Results obtained confirm the poor representation of both RAMLA- and FBP-reconstructed PET data by the Poisson distribution. We demonstrate that the noise in RAMLA-reconstructed PET images is very well characterized by gamma distribution followed closely by normal distribution, while FBP produces comparable conformity with both normal and gamma statistics.

(18)F-3'-Deoxy-3'-fluorothymidine ((18)F-FLT) is a PET tracer that accumulates in proliferating tissues. The current study was undertaken to determine whether equilibrative nucleoside transporter 1 (ENT1) is important for (18)F-FLT uptake in normal tissues and tumors.ENT1-knockout (ENT1(-/-)) mice were generated and compared with wild-type (ENT1(+/+)) mice using small-animal (18)F-FLT PET. In addition, ENT1(+/+) mice were also injected with the ENT1 inhibitor nitrobenzylmercaptopurine ribonucleoside phosphate (NBMPR-P) at 1 h before radiotracer injection, followed by (18)F-FLT small-animal PET. Tissues of interest were analyzed for thymidine kinase 1 and nucleoside transporters by immunoblotting and immunohistochemistry, respectively, and plasma thymidine levels were analyzed by liquid chromatography-mass spectrometry. Human lung carcinoma A549 cells were stably transfected with pSUPER-producing short-hairpin RNA against human ENT1 (hENT1) or a scrambled sequence with no homology to mammalian genes (A549-pSUPER-hENT1 and A549-pSUPER-SC, respectively). Cultured transfected cells were characterized for hENT1 transcript levels and (18)F-FLT uptake using real-time polymerase chain reaction and (3)H-FLT uptake assays, respectively. Transfected A549 cells were grown as xenograft tumors in NIH-III mice, which were analyzed by (18)F-FLT small-animal PET.Compared with noninjected ENT1(+/+) mice, ENT1(+/+) mice injected with NBMPR-P and ENT1(-/-) mice displayed a reduced percentage injected dose per gram (%ID/g) for (18)F-FLT in the blood (84 and 81%, respectively) and an increased %ID/g for (18)F-FLT in the spleen (188 and 469%, respectively) and bone marrow (266 and 453%, respectively). ENT1(-/-) mice displayed 1.65-fold greater plasma thymidine levels than did ENT1(+/+) mice. Spleen tissue from ENT1(+/+) and ENT1(-/-) mice displayed similar thymidine kinase 1 protein levels and significant concentrative nucleoside transporter 1 and 3 staining. Compared with A549-pSUPER-SC cells, A549-pSUPER-hENT1 cells displayed 0.45-fold hENT1 transcript levels and 0.68-fold (3)H-FLT uptake. Compared with A549-pSUPER-SC xenograft tumors, A549-pSUPER-hENT1 xenograft tumors displayed 0.76-fold %ID/g values (ex vivo gamma-counts) and 0.65-fold maximum standardized uptake values (PET image analysis) for (18)F-FLT uptake at 1 h after tracer injection.Loss of ENT1 activity significantly affected (18)F-FLT biodistribution in mice and (18)F-FLT uptake in xenograft tumors, suggesting that nucleoside transporters are important mediators of (18)F-FLT uptake in normal and transformed cells.

The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of smallanimal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult. Methods: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: micro- PET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET. Results: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity. Conclusion: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand. This work was funded by the Natural Sciences and Engineering Research Council of Canada under Discovery Grant 341628-2007. No other potential conflict of interest relevant to this article was reported. En prensa

Purpose: To determine the effect of geometric uncertainties in the seed positions in a COMS eye plaque on the central axis (CAX) dose. Methods: A Silastic insert was placed into a photopolymer 3D printed 16 mm COMS plaque, which was then positioned onto a custom-designed PMMA eye phantom. High resolution 3D images were acquired of the setup using a Siemens Inveon microPET/CT scanner. Images were acquired with the plaque unloaded and loaded with IsoAid I-125 seed shells (lack of silver core to minimize metal artifacts). Seed positions and Silastic thickness beneath each slot were measured. The measured seed coordinates were used to alter the seed positions within a standard 16 mm COMS plaque in Plaque Simulator v5.7.3 software. Doses along the plaque CAX were compared for the original and modified plaque coordinates using 3.5 mCi seeds with treatment times set to deliver 70 Gy to tumour apexes of 3.5, 5, and 10 mm height. Results: The majority of seeds showed length-wise displacement, and all seeds showed displacement radially outward from the eye center. The average radial displacement was 0.15 mm larger than the expected 1.4 mm offset, approximately half of which was due to increased Silastic thickness beneath each slot. The CAX doses for the modified seed positions were consistently lower for all tumour heights due to geometric displacement of the seeds; dose differences were found to increase to a maximum of 2.6% at a depth of ∼10 mm, after which they decreased due to the inverse square dose fall-off minimizing this effect. Conclusion: This work presents initial results of a broader dosimetric uncertainty evaluation for fully loaded COMS eye plaques and demonstrates the effects of seed positioning uncertainties. The small shifts in seed depths had noticeable effects on the CAX doses indicating the importance of careful Silastic loading. Funding provided by Alberta Cancer Foundation Grant #26655, Vanier Canada Graduate Scholarship, and Alberta Innovates Health Sciences Graduate Studentship

Purpose. The aim of this work is to develop a complete treatment planning procedure for radiation therapy of intracranial lesions based solely on 3T magnetic resonance imaging (MRI), i.e. MRI simulation. Methods. The proposed 3T MR-based radiotherapy treatment planning procedure consists of converting the MR images into CT-like images by assigning electron density information (related to CT values) to organ structures. Firstly, the 3D distortion field present in the MR volumes is determined and rectified by using an in-house developed distortion correction method. The MR volumes are segmented into anatomical structures, i.e. brain, bone and scalp, by using a combination of the "Profile" and Autocontouring" tools available on Pinnacle (Philips MedicalSystems) treatment planning system (TPS). Bulk electron density values are assigned to the 3D volumes in Pinnacle by overriding thei default MR values. Once the MR images contain the target volume along with the electron density information, they are ready to be used for dose calculations. The resulting CT+MR and MR only based plans were compared in terms of isodose distributions and dose-volume histrograms (DVHs). For plan ranking we use a tumor-control probability (TCP)-based procedure for heterogeneous irradiation,which does not require the knowledge of radiobiological parameters. Results. For all patients investigated, the 3T MR only and CT+MR-based plans are in good agreement in terms of isodose distributions, DVHs and TCPs (within 1%) following our clinical criteria. Conclusions. The proposed 3T MR only based treatment planning procedure performs as good as thestandard clinical procedure that relies on both CT and MR studies. MRI simulation can significantly reduce the patient treatment cost and save staff and machine time, and avoid any errors that may be associated with the image fusion process. Izhodišča. Namen pričujoče raziskave je bil oblikovati postopek za načrtovanjeobsevanja možganskih sprememb s pomočjo 3T magnetne resonančne preiskave (MRI), t.i. MRI simulacije. Metode. Pri načrtovanju obsevanja s 3T MR načinom spremenimo MR slike v CT-ju podobne slike in pri tem uporabimo podatke elektronske gostote organov. Ker pri MR volumnih ugotavljamo 3D izkrivljanje, smo razvili posebno korektivno metodo. Najprej smo MR volumne razdelili glede na anatomske strukture kot so možgani, kosti in koža ter pri tem uporabili orodja programa Pinnacle (Philips Medical Systems), ki je del sistema za načrtovanja obsevanja (treatment planning system - TPS). Izračun smo naredili, ko smo MR slikam določili tarčne volumne z elektronsko gostoto. Primerjali smo načrte obsevanja s pomočjo CT+MR tehnike in samo MR simulacije.Zanimala nas je razporeditev izodoz in dozavolumen histogrami (dose-volume histograms - DVHs). Ob ugotavljanju heterogenosti obsevanja smo ocenjevali verjetnost tumorske kontrole (tumor-control probability - TCP), karni zahtevalo poznavanje radiobioloških parametrov. Rezultati. Pri vseh bolnikih smo ugotovili, da so obsevalni načrti s CT+MR tehniko in 3T MR tehniko podobni, bodisi ob primerjavi izodozne distribucije, bodisi DVHs in TCP. Razlike niso bile večje kot 1%, če smo upoštevali naše klinične kriterije. Zaključki. Uporaba predlagane 3T MR tehnike načrtovanja obsevanja je enako natančna kot uporaba kombinacije CT+MR tehnike. MRI simulacija obsevanja lahko poceni obravnavo bolnikov in prihrani čas obravnave, če jo primerjamo s CT+MR tehniko, prav tako pa se lahko izognemo napakam, ki bi lahko nastale pri združevanju CT in MR slik.

Purpose: To compare the radiation dose to normal organs from the radio-iodinated, hypoxia-binding radiosensitizer iodoazomycin arabinoside (IAZA) for three different isotopes of iodine. Methods: Dosimety studies with normal volunteers had been carried out with [123I]IAZA, a drug binding selectively to hypoxic sites. Two other isotopes of iodine, 131I and 124I, offer the opportunity to use IAZA as an agent for radioisotope therapy and as an imaging tracer for Positron Emission Tomography. Radioisotope dosimetry for 131I and 124I was performed by first deriving from the [123I]IAZA studies biological uptake and excretion data. The cumulated activities for 131I or 124I where obtained by including their half-lives when integrating the biological data and then extrapolating to infinite time points considering a) physical decay only or b) physical and biological excretion. Doses were calculated using the Medical Internal Radiation Dose (MIRD) schema (OLINDA1.1 code, Vanderbilt 2007). Results: Compared to 123I, organ doses were elevated on average by a factor 6 and 9 for 131I and 124I, respectively, if both physical decay and biological excretion were modeled. If only physical decay is considered, doses increase by a factor 18 (131I) and 19 (124I). Highest organ doses were observed in intestinal walls, urinary bladder and thyroid. Effective doses increased by a factor 11 and 14 for 131I and 124I, respectively, if biological and physical decay are present. Purely physical decay yields a 23-fold increase over 123I for both, 131I and 124I. Conclusion: Owing to the significant dose increase, caused by their longer half life and the approximately 10 times larger electronic dose deposited in tissue per nuclear decay, normal tissue doses of IAZA labeled with 131I and 124I need to be carefully considered when designing imaging and therapy protocols for clinical trials. Effective blocking of iodine uptake in the thyroid is essential. Alberta Innovates - Health Solutions (AIHS) and Canadian Institutes of Health Research (CIHR)

Purpose: To apply factor analysis technique to a sequence of 11C‐DTBZ dynamic PETimages to healthy and diseased subjects in order to extract factor curves (or time activity curves) and associated factor images and develop a metric to detect extent of Parkinson's disease. Methods: Philips Gemini (C) PET/CT scanner (with 4mm isotropic voxels) is used to collect a dynamic dataset consisting of a time sequence of 16 frames (with unequal temporal spacing) of the brain from healthy and diseased subjects. Several image preprocessing techniques (e.g. noise reduction using singular value decomposition, voxel‐averaging) are used on these dynamic datasets prior to implementing factor analysis using projected gradient method in the framework of non‐negative matrix factorization to extract physiologically meaningful structures. A priori information (region‐of‐interest based time activity curves) is used to warm start the optimization process in order to reduce the number of possible solutions. Results: The factor analysis technique separates each dynamic dataset into two time‐dynamic factors — one factor represents the striatum (directly related to the disease) while the other factor represents the non‐striatum tissues. The factor curves and images related to the former show clear difference in the tracer uptake among the healthy and diseased subjects. Our metric, which relies on such difference, indicates that the tracer uptake in striatum tissue for the healthy subject is roughly four times higher than that of the diseased subject. Conclusions: This study suggests that the technique can decompose large dynamic datasets into parts‐based images (or volumes) that represent the underlying physiological structures, and has the potential to significantly aid in the review process for evaluating dynamic datasets by clinicians. The technique is not limited to dynamic PETimages and can be applied to any sequence of dynamic images.