Exploration of Coincidence Detection of Cascade Photons to Enhance Preclinical Multi-Radionuclide SPECT Imaging.

We proposed a technique of coincidence detection of cascade photons (CDCP) to enhance preclinical SPECT imaging of therapeutic radionuclides emitting cascade photons, such as Lu-177, Ac-225, Ra-223, and In-111. We have carried out experimental studies to evaluate the proposed CDCP-SPECT imaging of low-activity radionuclides using a prototype coincidence detection system constructed with large-volume cadmium zinc telluride (CZT) imaging spectrometers and a pinhole collimator. With In-111 in experimental studies, the CDCP technique allows us to improve the signal-to-contamination in the projection (Projection-SCR) by ~53 times and reduce ~98% of the normalized contamination. Compared to traditional scatter correction, which achieves a Projection-SCR of 1.00, our CDCP method boosts it to 15.91, showing enhanced efficacy in reducing down-scattered contamination, especially at lower activities. The reconstructed images of a line source demonstrated the dramatic enhancement of the image quality with CDCP-SPECT compared to conventional and triple-energy-window-corrected SPECT data acquisition. We also introduced artificial energy blurring and Monte Carlo simulation to quantify the impact of detector performance, especially its energy resolution and timing resolution, on the enhancement through the CDCP technique. We have further demonstrated the benefits of the CDCP technique with simulation studies, which shows the potential of improving the signal-to-contamination ratio by 300 times with Ac-225, which emits cascade photons with a decay constant of ~0.1 ns. These results have demonstrated the potential of CDCP-enhanced SPECT for imaging a super-low level of therapeutic radionuclides in small animals.

Economical droplet-based microfluidic production of [18F]FET and [18F]Florbetaben suitable for human use.

Current equipment and methods for preparation of radiopharmaceuticals for positron emission tomography (PET) are expensive and best suited for large-scale multi-doses batches. Microfluidic radiosynthesizers have been shown to provide an economic approach to synthesize these compounds in smaller quantities, but can also be scaled to clinically-relevant levels. Batch microfluidic approaches, in particular, offer significant reduction in system size and reagent consumption. Here we show a simple and rapid technique to concentrate the radioisotope, prior to synthesis in a droplet-based radiosynthesizer, enabling production of clinically-relevant batches of [18F]FET and [18F]FBB. The synthesis was carried out with an automated synthesizer platform based on a disposable Teflon-silicon surface-tension trap chip. Up to 0.1 mL (4 GBq) of radioactivity was used per synthesis by drying cyclotron-produced aqueous [18F]fluoride in small increments directly inside the reaction site. Precursor solution (10 µL) was added to the dried [18F]fluoride, the reaction chip was heated for 5 min to perform radiofluorination, and then a deprotection step was performed with addition of acid solution and heating. The product was recovered in 80 µL volume and transferred to analytical HPLC for purification. Purified product was formulated via evaporation and resuspension or a micro-SPE formulation system. Quality control testing was performed on 3 sequential batches of each tracer. The method afforded production of up to 0.8 GBq of [18F]FET and [18F]FBB. Each production was completed within an hour. All batches passed quality control testing, confirming suitability for human use. In summary, we present a simple and efficient synthesis of clinically-relevant batches of [18F]FET and [18F]FBB using a microfluidic radiosynthesizer. This work demonstrates that the droplet-based micro-radiosynthesizer has a potential for batch-on-demand synthesis of 18F-labeled radiopharmaceuticals for human use.

Design and performance of an epithermal neutron flux detector using 55Mn(n,γ)56Mn reaction for BNCT.

The measurement of the epithermal neutron (0.5 eV - 10 keV) flux of a boron neutron capture therapy (BNCT) treatment beam is a critical issue to its quality assessment and evaluation of the radiation dose to the treated patients. In this work, an activation detector using 55Mn(n,γ)56Mn reaction is designed by Monte Carlo simulations to measure the epithermal neutron flux of BNCT treatment beam. The detector is spherical and it has an absorber/moderator/absorber/manganese (Mn) foil arrangement from outside to inside. The activation material, i.e., Mn foil, is located at the geometrical center of the detector. After the design, the performance of the detector is evaluated by Monte Carlo simulations using the treatment neutron beams of operating reactor-based BNCT facilities. The results and related analysis indicate that the proposed detector will be efficiently applicable in the quality assessment of BNCT treatment beam and evaluation of the radiation dose to the treated patients.

In silico dosimetry of low-dose rate brachytherapy using radioactive nanoparticles.

PURPOSE: Nanoparticles (NPs) with radioactive atoms incorporated within the structure of the NP or bound to its surface, functionalized with biomolecules are reported as an alternative to low-dose-rate seed-based brachytherapy. In this study, authors report a mathematical dosimetric study on low-dose rate brachytherapy using radioactive NPs. METHOD: Single-cell dosimetry was performed by calculating cellular S-values for spherical cell model using Au-198, Pd-103 and Sm-153 NPs. The cell survival and tumor volume versus time curves were calculated and compared to the experimental studies on radiotherapeutic efficiency of radioactive NPs published in the literature. Finally, the radiotherapeutic efficiency of Au-198, Pd-103 and Sm-153 NPs was tested for variable: administered radioactivity, tumor volume and tumor cell type. RESULT: At the cellular level Sm-153 presented the highest S-value, followed by Pd-103 and Au-198. The calculated cell survival and tumor volume curves match very well with the published experimental results. It was found that Au-198 and Sm-153 can effectively treat highly aggressive, large tumor volumes with low radioactivity. CONCLUSION: The accurate knowledge of uptake rate, washout rate of NPs, radio-sensitivity and tumor repopulation rate is important for the calculation of cell survival curves. Self-absorption of emitted radiation and dose enhancement due to AuNPs must be considered in the calculations. Selection of radionuclide for radioactive NP must consider size of tumor, repopulation rate and radiosensitivity of tumor cells. Au-198 NPs functionalized with Mangiferin are a suitable choice for treating large, radioresistant and rapidly growing tumors.

177Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α1-Microglobulin (A1M), Including Kidney Damage Assessment Using 99mTc-MAG3 Imaging.

Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α1-microglobulin (A1M) together with 177-Lutetium (177Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity. Nude mice with subcutaneous LNCaP xenografts were injected with 50 or 100 MBq of [177Lu]Lu-PSMA-617, with or without injections of recombinant A1M (rA1M) (at T = 0 and T = 24 h). Kidney absorbed dose was calculated to 7.36 Gy at 4 days post a 100 MBq injection. Activity distribution was imaged with Single-Photon Emission Computed Tomography (SPECT) at 24 h. Tumor volumes were measured continuously, and kidneys and blood were collected at termination (3-4 days and 3-4 weeks after injections). In a parallel set of experiments, mice were given [177Lu]Lu-PSMA-617 and rA1M as above and dynamic technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3) SPECT imaging was performed prior to injection, and 3- and 6-months post injection. Blood and urine were continuously sampled. At termination (6 months) the kidneys were resected. Biomarkers of kidney function, expression of stress genes and kidney histopathology were analyzed. [177Lu]Lu-PSMA-617 uptake, in tumors and kidneys, as well as treatment efficacy did not differ between rA1M and vehicle groups. In mice given rA1M, [99mTc]Tc-MAG3 imaging revealed a significantly higher slope of initial uptake at three months compared to mice co-injected with [177Lu]Lu-PSMA-617 and vehicle. Little or no change compared to control was seen in urine albumin, serum/plasma urea levels, RT-qPCR analysis of stress response genes and in the kidney histopathological evaluation. In conclusion, [99mTc]Tc-MAG3 imaging presented itself as a sensitive tool to detect changes in kidney function revealing that administration of rA1M has a potentially positive effect on kidney perfusion and tubular function when combined with [177Lu]Lu-PSMA-617 therapy. Furthermore, we could show that rA1M did not affect anti-PSMA radioligand therapy efficacy.

Left ventricle function assessment using gated first-pass 18F-FDG PET: Validation against equilibrium radionuclide angiography.

PURPOSE: We appraised the feasibility of left ventricle (LV) function assessment using gated first-pass 18F-FDG PET, and assessed the concordance of the produced measurements with equilibrium radionuclide angiography (ERNA). MATERIALS AND METHODS: Twenty-four oncologic patients benefited from 99mTc-labeled red-blood-cell ERNA, in planar mode (all patients) and using SPECT (22 patients). All patients underwent gated first-pass 18F-FDG cardiac PET. Gated dynamic PET images were reconstructed over 1 minute during tracer first-pass inside the LV and post-processed using in-house software (TomPool). After re-orientation into cardiac canonical axes and adjustment of the valves plane using a phase image, pseudo-planar PET images obtained by re-projection were automatically segmented using thresholded region growing and gradient-based delineation to produce an LV ejection fraction (EF) estimate. PET images were also post-processed in fully-tomographic mode to produce LV end diastole volume (EDV), end systole volume (ESV), and EF estimates. Concordance was assessed using Lin's concordance (ccc) and Bland-Altman analysis. Reproducibility was assessed using the coefficient of variation (CoV) and intra-class correlation (ICC). RESULTS: Pseudo-planar PET EF estimates were concordant with planar ERNA (ccc = 0.81, P < .001) with a bias of 0% (95% CI [- 2%; 3%], limits of agreement [- 11%; 12%]). Reproducibility was excellent and similar for both methods (CoV = 2 ± 1% and 3 ± 2%, P = NS; ICC = 0.97 and 0.92, for PET and ERNA, respectively). Measurements obtained in fully-tomographic mode were concordant with SPECT ERNA: ccc = 0.83 and bias = - 3 mL for LV EDV, ccc = 0.92 and bias = 0 mL for LV ESV, ccc = 0.89 and bias = - 1% for LV EF (all P values < .001 for ccc, all biases not significant). CONCLUSIONS: Gated first-pass 18F-FDG PET might stand as a relevant alternative to ERNA for LV function assessment, enabling a joint evaluation of both therapeutic response and cardiac toxicity in oncologic patients receiving cardiotoxic chemotherapy.

Dosimetry study on Auger electron-emitting nuclear medicine radioisotopes in micrometer and nanometer scales using Geant4-DNA simulation.

PURPOSE: Dosimetry of Auger electron-emitting nuclear medicine radioisotopes on cellular and DNA scales is essential in order to assess the biological effects and damage of these radioisotopes to the DNA molecule. This study examined the effects of widely used radioisotopes in nuclear medicine and also two therapeutic radioisotopes in the scale of micrometer and nanometer. METHODS: In this paper, on cell scale (micrometer scale), the S-values for widely used Auger electron-emitting diagnostic radioisotopes 123I, 125I, 99mTc, 67Ga, 201Tl and 111In and two therapeutic radioisotopes of 131I and 211At in three different geometrical cell models (spherical, elliptical and cubic) were calculated using Geant4-DNA and the results were compared with the results of other simulation codes as well as the MIRD technique. On DNA scale (nanometer scale), the average number of DNA strand breaks (SSB and DSB) resulting from the direct and indirect effects was calculated for the specified radioisotope. RESULTS: The results showed that in the cell scale, S-values of the diagnostic radioisotopes were mostly greater than the S-values of the therapeutic radioisotope 131I, but they were less those of 211At. On DNA scale, two different geometric models of DNA molecule were simulated and the results of these two models were compared with each other, as well as with the literature. The results showed that the geometric shape of sugar-phosphate groups has a significant effect on the break rates of DNA molecules. CONCLUSIONS: Among the widely used diagnostic radioisotopes, 201Tl and 125I had the greatest effect on the rate of SSBs and DSBs, respectively, while the 131I therapeutic radioisotope almost had no effect and therapeutic radioisotope of 211At had a moderate effect on the number of breaks.

Comparison of different calculation techniques for absorbed dose assessment in patient specific peptide receptor radionuclide therapy.

AIM: The present work concerns the comparison of the performances of three systems for dosimetry in RPT that use different techniques for absorbed dose calculation (organ-level dosimetry, voxel-level dose kernel convolution and Monte Carlo simulations). The aim was to assess the importance of the choice of the most adequate calculation modality, providing recommendations about the choice of the computation tool. METHODS: The performances were evaluated both on phantoms and patients in a multi-level approach. Different phantoms filled with a 177Lu-radioactive solution were used: a homogeneous cylindrical phantom, a phantom with organ-shaped inserts and two cylindrical phantoms with inserts different for shape and volume. A total of 70 patients with NETs treated by PRRT with 177Lu-DOTATOC were retrospectively analysed. RESULTS: The comparisons were performed mainly between the mean values of the absorbed dose in the regions of interest. A general better agreement was obtained between Dose kernel convolution and Monte Carlo simulations results rather than between either of these two and organ-level dosimetry, both for phantoms and patients. Phantoms measurements also showed the discrepancies mainly depend on the geometry of the inserts (e.g. shape and volume). For patients, differences were more pronounced than phantoms and higher inter/intra patient variability was observed. CONCLUSION: This study suggests that voxel-level techniques for dosimetry calculation are potentially more accurate and personalized than organ-level methods. In particular, a voxel-convolution method provides good results in a short time of calculation, while Monte Carlo based computation should be conducted with very fast calculation systems for a possible use in clinics, despite its intrinsic higher accuracy. Attention to the calculation modality is recommended in case of clinical regions of interest with irregular shape and far from spherical geometry, in which Monte Carlo seems to be more accurate than voxel-convolution methods.

A simulation study on beam property of 124Sb-Be isotope-based neutron for BNCT.

The 9Be(γ,n) neutrons with the energies at 21-24 keV generated by 1.691 MeV photons from 124Sb was investigated as a source of epithermal neutrons for BNCT, using PHITS code. A beam shaping assembly composed of 13 mm thick Be target, a gamma ray shield made of 30 cm thick Bi, and a reflector of 30 cm thick Pb satisfied the beam requirements of IAEA-TECDOC-1223. The needed 124Sb activity was estimated in the order of 1016-1017 Bq. Feasibility of BNCT using 124Sb-Be neutrons would be influenced by the capability of periodic supply of short-lived 124Sb (half-life: 60 days) with such high activity.

Texture analysis in 177Lu SPECT phantom images: Statistical assessment of uniformity requirements using texture features.

The purpose of this study was to apply texture analysis (TA) to evaluate the uniformity of SPECT images reconstructed with the 3D Ordered Subsets Expectation Maximization (3D-OSEM) algorithm. For this purpose, a cylindrical homogeneous phantom filled with 177Lu was used and a total of 24 spherical volumes of interest (VOIs) were considered inside the phantom. The location of the VOIs was chosen in order to define two different configurations, i.e. gravity and radial configuration. The former configuration was used to investigate the uniformity of distribution of 177Lu inside the phantom, while the latter configuration was used to investigate the lack of uniformity from center towards edge of the images. For each VOI, the trend of different texture features considered as a function of 3D-OSEM updates was investigated in order to evaluate the influence of reconstruction parameters. TA was performed using CGITA software. The equality of the average texture feature trends in both spatial configurations was assumed as the null hypothesis and was tested by functional analysis of variance (fANOVA). With regard to the gravity configuration, no texture feature rejected the null hypothesis when the number of subsets increased. For the radial configuration, the statistical analysis revealed that, depending on the 3D-OSEM parameters used, a few texture features were capable of detecting the non-uniformity of 177Lu distribution inside the phantom moving from the center of the image towards its edge. Finally, cross-correlation coefficients were calculated to better identify the features that could play an important role in assessing quality assurance procedures performed on SPECT systems.

Dosimetry Assessment of Injected 89Zr-Labeled Monoclonal Antibodies in Humans.

In this study, the behavior dynamics of Zirconium-89 (89Zr)-labeled monoclonal antibodies (MAbs) after injection into the human body were modeled. This modified biokinetic model can be used for dose assessment, not only for 89Zr-labeled MAb tumor visualization, but also for diagnostic and therapeutic radiation with MAb labeled with other radionuclides. A modified biokinetic model was created based on experimental data from previously published studies. Cumulative 89Zr activity in organs and tissues per Bq of administered activity was calculated using the WinAct program. For most organs receiving the highest radiation dose, average absorbed doses were estimated using IDAC version 2.1 software. The results from the modeled calculations were compared with recently published results from studies of real patients. The calculations revealed that organs with the highest dose were the spleen, liver, kidneys and red bone marrow, at 1.54, 1.33, 0.81 and 0.82 mGy/MBq, respectively. In the modified biokinetic model, with MAb injection, organs exhibiting the highest dose were liver, heart wall, spleen, red bone marrow and pancreas, at 1.05, 0.93, 0.79, 0.69 and 0.67 mGy/MBq, respectively.

Utilization of Chemical Deposition Technique for Preparation of Miniature 170Tm Sources and Preliminary Quality Assessment for Potential Use in Brachytherapy.

OBJECTIVE: This article describes the preparation of a 170Tm source by chemical deposition technique, its encapsulation in a titanium holder, and preliminary quality evaluation for potential utility as a brachytherapy source. METHODS: The procedure consisted of electrodeposition of Ni on a Cu wire followed by chemical deposition of 170Tm on it. Influence of feed solution pH, carrier Tm concentration, and reaction time were studied for optimum deposition of 170Tm on substrate. After sealing the source core in a titanium capsule, quality control tests were performed. Distribution of 170Tm on substrate was evaluated by autoradiography. Inactive Tm source was characterized by scanning electron microscope (SEM) and energy-dispersive X-ray (EDS) analyses. RESULTS: Under optimized conditions (pH 5, 10 µg Tm carrier, 5 h), 170Tm source core could be prepared by deposition of >95% of 170Tm radioactivity on substrate. Swipe tests and immersion tests on encapsulated sources confirmed that removable radioactivity and radioactivity leakage levels were within stipulated limits. Autoradiography of 170Tm source confirmed uniformity of radioactivity distribution. While SEM analysis confirmed good adhesion of Tm on substrate, EDS analysis confirmed elemental constituents of the Tm-deposited substrate. CONCLUSION: The objective of preparing a 170Tm source by chemical deposition for potential brachytherapy applications could be successfully achieved.

Determination of Gamma Camera's Calibration Factors for Quantitation of Diagnostic Radionuclides in Simultaneous Scattering and Attenuation Correction.

OBJECTIVE: The characterization of cancerous tissue and bone metastasis can be distinguished by accurate assessment of accumulated uptake and activity from different radioisotopes. The various parameters and phenomena such as calibration factor, Compton scattering, attenuation and penetration intrinsicallyinfluence calibration equation, and the qualification of images as well. METHODS: The camera calibration factor (CF) translates reconstructed count map into absolute activity map, which is determined by both planar and tomographic scans using different phantom geometries. In this study, the CF for radionuclides of Tc-99m and Sm-153 in soft tissue and bone was simulated by the Monte Carlo method, and experimental results were obtained in equivalent tissue and bone phantoms. It may be employed for the simultaneous correction of the scattering and attenuation rays interacted with the camera, leading to corrected counts. Also, the target depth (d) may be estimated by a combination of scattering and photoelectric functions, which we have published before. RESULTS: The calibrated equations for soft tissue phantom for the radionuclides were obtained by RTc = - 10d+ 300 and RSm = -8d + 100, and the relative errors between the simulated and experimental results were 4.5% and 3.1%, respectively. The equations for bone phantom were RTc = -30d + 300 and RSm = - 10d + 100, and the relative errors were 5.4% and 5.6%. The R and d are in terms of cpm/mCi and cm. Besides, the collimators' impact was evaluated on the camera response, and the relevant equations were obtained by the Monte Carlo method. The calibrated equations as a function of various radiation angles on the center of camera's cells without using collimator indicated that both sources have the same quadratic coefficient by -2E-08 and same vertical width from the origin by 8E-05. CONCLUSION: The presented procedure may help determine the absorbed dose in the target and likewise optimize treatment planning.

Simulation of radionuclide atmospheric dispersion and dose assessment for inhabitants of Tehran province after a hypothetical accident of the Tehran Research Reactor.

Radiological dose assessment is one of the main categories of safety assessment for nuclear reactors and facilities. The radiation risks to the public and to the environment that may arise from these facilities have to be assessed and, if necessary, controlled. The main objective of this paper is the assessment of radiation doses to residents of Tehran province after a hypothetical accident of the Tehran Research Reactor (TRR) including the determination of any protective actions that might be needed for the benefit of people's health. The concentration of radionuclides in air and deposited on the ground surface as a result of a hypothetical radionuclide release from the TRR, following a hypothetical accident scenario, have been calculated by the HYSPLIT computer code. Simulations were performed using selected source terms taken from the TRR Final Safety Analysis Report (FSAR). Meteorological data of the Air Resources Laboratory of the National Oceanic and Atmospheric Administration (NOAA) have been used in these calculations. The simulation results indicate that maximum annual total effective dose equivalent values for the residents of the Tehran province are less than the protective action dose limits. Thus, it is concluded that during this hypothetical accident in the TRR, required safety due to public radiation is achieved and the residents of Tehran province are safe under a TRR accident condition.

Electron-tracking Compton camera imaging of technetium-95m.

Imaging was conducted using an electron tracking-Compton camera (ETCC), which measures γ-rays with energies in the range of 200-900 keV from 95mTc. 95mTc was produced by the 95Mo(p, n)95mTc reaction on a 95Mo-enriched target. A method for recycling 95Mo-enriched molybdenum trioxide was employed, and the recycled yield of 95Mo was 70%-90%. Images were obtained with the gate of three energies. The results showed that the spatial resolution increases with increasing γ-ray energy, and suggested that the ETCC with high-energy γ-ray emitters such as 95mTc is useful for the medical imaging of deep tissue and organs in the human body.

Assessment of natural radionuclides mobility in a phosphogypsum disposal area.

The phosphogypsum (PG) stacks located at Huelva (SW Spain) store about 100 Mt of PG, and covers a surface of 1000 ha. It has been very well established in many studies that this waste contains significant U-series radionuclides concentrations, with average activity concentrations rounding the 650, 600, 400 and 100 Bq kg-1 for 226Ra, 210Po, 230Th and 238U, respectively. However, the radionuclide transfer from this repository into the environment by the aquatic pathway will depend on the mobility of each radionuclide. The mobility of the natural radionuclides (U-isotopes, Th-isotopes, 226Ra, and 210Po) contained in the PG piles were evaluated by using the optimized BCR sequential extraction procedure (BCR "Community Bureau of Reference"). The radionuclides were measured in the liquid fractions by alpha-particle spectrometry with semiconductor PIPS detectors. In addition, to validate the obtained results, waters from different locations of the PG piles (pore-water, perimeter channel and edge outflow leachates) were taken and the alpha emitter radionuclides determined. Uranium presents the highest mobility, being its total mobile fraction in the PG around 70%, while 210Po and 226Ra present an intermediate mobility of (around 50% and 30%, respectively). And finally, the Th-isotopes have very low mobility (mobile fraction < 5%), being fixed to the residual fraction. It is noteworthy that this behaviour has been also found in the water samples taken from the stacks, demonstrating that this sequential leaching operational methodology is a useful tool for assessing the release capacity of radionuclides by inorganic wastes.

Assessment of PSMA targeting ligands bearing novel chelates with application to theranostics: Stability and complexation kinetics of 68Ga3+, 111In3+, 177Lu3+ and 225Ac3.

INTRODUCTION: Recent successes in the treatment of metastatic castration-resistant prostate cancer (mCRPCa) by systemic endoradiotherapy has sparked renewed interest in developing small molecule ligands targeting prostate-specific membrane antigen (PSMA) and chelators capable of stable complexation of metal radionuclides for imaging and therapy. As the size and coordination number of metals for imaging, such as 68Ga3+, and for targeted therapy, such as 177Lu3+ and 225Ac3+, are substantially different, they may show a preference for macrocycles of different denticity. We have prepared three simple conjugates that target PSMA and form radiometal complexes through coordination by either octa-, deca-, or dodecadentate tetraazacyclododecane chelators. The complex formation and metal ion selectivity of these constructs were determined at two relevant temperatures, complex stability was examined in vitro, and tumor targeting was demonstrated in preclinical PCa models with a view towards identifying a candidate with potential value as a theranostic agent for the imaging and therapy of mCRPCa. METHODS: Three bifunctional chelates with high denticity, including the octadentate chelate DOTA, the decadentate 3p-C-DEPA and a novel dodecadentate analogue of DEPA, were synthesized and conjugated to a glutamate-urea-lysine (EuK) pharmacophore (EuK-DOTA, EuK-107 and EuK-106, respectively) to enable targeting of PSMA. The metal ion selectivity for each construct was determined by incubation at 25 °C and 95 °C with the trivalent radiometals 68Ga3+, 111In3+, 177Lu3+ and 225Ac3+. PSMA binding affinity was determined by competitive binding using LNCaP cells, while in vivo tumor targeting of the 68Ga-labeled constructs was examined by positron emission tomography (PET) in LNCaP xenograft tumor-bearing mice. RESULTS: PMSA affinities (IC50 values) were 13.3 ± 0.9 nM for EuK-DOTA, 18.0 ± 3.7 nM for EuK-107 and 42.6 ± 6.6 nM for EuK-106. EuK-107 and EuK-DOTA proved to rapidly and near quantitatively complex 68Ga3+, 111In3+, 177Lu3+ and 225Ac3+ at 95 °C, with EuK-107 also rapidly complexing 111In3+ and 177Lu3+ at 25 °C. The inability of EuK-106 to chelate 177Lu3+ and 225Ac3+ suggests that size of the cavity of the macrocylic ring may be more critical than the number of donor groups for the chelation of larger radiometals. In vivo, 68Ga-EuK-107 proved to have similar uptake to 68Ga-DKFZ-PSMA-617, a theranostic ligand currently in clinical evaluation, in a PSMA positive xenograft tumor model. CONCLUSIONS: The broad metal ion selectivity, good in vitro affinity for PSMA and good in vivo tumor targeting suggest that EuK-107, with the 3p-C-DEPA chelator, merits further evaluation as a theranostics construct in prostate cancer.

Absorbed dose evaluation of Auger electron-emitting radionuclides: impact of input decay spectra on dose point kernels and S-values.

The aim of this study was to investigate the impact of decay data provided by the newly developed stochastic atomic relaxation model BrIccEmis on dose point kernels (DPKs - radial dose distribution around a unit point source) and S-values (absorbed dose per unit cumulated activity) of 14 Auger electron (AE) emitting radionuclides, namely 67Ga, 80mBr, 89Zr, 90Nb, 99mTc, 111In, 117mSn, 119Sb, 123I, 124I, 125I, 135La, 195mPt and 201Tl. Radiation spectra were based on the nuclear decay data from the medical internal radiation dose (MIRD) RADTABS program and the BrIccEmis code, assuming both an isolated-atom and condensed-phase approach. DPKs were simulated with the PENELOPE Monte Carlo (MC) code using event-by-event electron and photon transport. S-values for concentric spherical cells of various sizes were derived from these DPKs using appropriate geometric reduction factors. The number of Auger and Coster-Kronig (CK) electrons and x-ray photons released per nuclear decay (yield) from MIRD-RADTABS were consistently higher than those calculated using BrIccEmis. DPKs for the electron spectra from BrIccEmis were considerably different from MIRD-RADTABS in the first few hundred nanometres from a point source where most of the Auger electrons are stopped. S-values were, however, not significantly impacted as the differences in DPKs in the sub-micrometre dimension were quickly diminished in larger dimensions. Overestimation in the total AE energy output by MIRD-RADTABS leads to higher predicted energy deposition by AE emitting radionuclides, especially in the immediate vicinity of the decaying radionuclides. This should be taken into account when MIRD-RADTABS data are used to simulate biological damage at nanoscale dimensions.

Radiological impact assessment to the environment due to waste from disposal of porcelain.

The present study aimed to assess the radiological parameters from gamma rays due to the uncontrolled disposal of porcelain waste to the environment. Qualitative and quantitative identification of radionuclides in the investigated samples was carried out by means of a high-purity germanium (HPGe) detector. The average activity concentrations of the local porcelain samples were measured as 208.28 Bq/kg for 226Ra, 125.73 Bq/kg for 238U, 84.94 Bq/kg for 232Th and 1033.61 Bq/kg for 40K, respectively. The imported samples had an average activity of 240.57 Bq/kg for 226Ra, 135.56 Bq/kg for 238U, 115.74 Bq/kg for 232Th and 1312.49 Bq/kg for 40K, respectively. Radiological parameters and the radium equivalent Raeq for the investigated samples were calculated. The external and internal hazard indices, representative level index (Iγ), alpha index (Iα), and the exemption level (Ix), were estimated to be higher than the recommended value (unity), while the average activity concentrations for the studied samples were higher than recommended levels. In conclusion, we are concerned that disposal of porcelain in the environment might be a significant hazard.