Establishment of a clinical SPECT/CT protocol for imaging of 161Tb.

BACKGROUND: It has been proposed, and preclinically demonstrated, that 161Tb is a better alternative to 177Lu for the treatment of small prostate cancer lesions due to its high emission of low-energy electrons. 161Tb also emits photons suitable for single-photon emission computed tomography (SPECT) imaging. This study aims to establish a SPECT protocol for 161Tb imaging in the clinic. MATERIALS AND METHODS: Optimal settings using various γ-camera collimators and energy windows were explored by imaging a Jaszczak phantom, including hollow-sphere inserts, filled with 161Tb. The collimators examined were extended low-energy general purpose (ELEGP), medium-energy general purpose (MEGP), and low-energy high resolution (LEHR), respectively. In addition, three ordered subset expectation maximization (OSEM) algorithms were investigated: attenuation-corrected OSEM (A-OSEM); attenuation and dual- or triple-energy window scatter-corrected OSEM (AS-OSEM); and attenuation, scatter, and collimator-detector response-corrected OSEM (ASC-OSEM), where the latter utilized Monte Carlo-based reconstruction. Uniformity corrections, using intrinsic and extrinsic correction maps, were also investigated. Image quality was assessed by estimated recovery coefficients (RC), noise, and signal-to-noise ratio (SNR). Sensitivity was determined using a circular flat phantom. RESULTS: The best RC and SNR were obtained at an energy window between 67.1 and 82.1 keV. Ring artifacts, caused by non-uniformity, were removed with extrinsic uniformity correction for the energy window between 67.1 and 82.1 keV, but not with intrinsic correction. Analyzing the lower energy window between 48.9 and 62.9 keV, the ring artifacts remained after uniformity corrections. The recovery was similar for the different collimators when using a specific OSEM reconstruction. Recovery and SNR were highest for ASC-OSEM, followed by AS-OSEM and A-OSEM. When using the optimized parameter setting, the resolution of 161Tb was higher than for 177Lu (8.4 ± 0.7 vs. 10.4 ± 0.6 mm, respectively). The sensitivities for 161Tb and 177Lu were 7.41 and 8.46 cps/MBq, respectively. CONCLUSION: SPECT with high resolution is feasible with 161Tb; however, extrinsic uniformity correction is recommended to avoid ring artifacts. The LEHR collimator was the best choice of the three tested to obtain a high-resolution image. Due to the complex emission spectrum of low-energy photons, window-based scatter correction had a minor impact on the image quality compared to using attenuation correction only. On the other hand, performing attenuation, scatter, and collimator-detector correction clearly improved image quality. Based on these data, SPECT-based dosimetry for 161Tb-labeled radiopharmaceuticals is feasible.

Kinetic study of uranium residue dissolution in ammonium carbonate media.

The purpose of this study was to determine the kinetics of the dissolution of a uranium residue in ammonium carbonate media. The residue is generated in the production of medical isotopes. The effects of parameters, such as varying peroxide and carbonate concentrations, dissolution time as well as temperature on the extraction rate have been separately studied. Results indicate complete dissolution of the residue at 60 °C, after 30 min, in ammonium carbonate solution enriched with hydrogen peroxide. The yield and rate of uranium extraction were found to increase as a function of both temperature, in the range of 25-60 °C, and hydrogen peroxide concentration. The extraction process was governed by chemical reaction as the activation energy was found to be 45.5 kJ/mol. The order of reaction with respect to uranium concentration was found to be approximately first order.

Biodistribution and dosimetry of 195mPt-cisplatin in normal volunteers. Imaging agent for single photon emission computed tomography.

UNLABELLED: 195mPt-cisplatin is regarded as a promising imaging agent for optimizing dosage in patients receiving cisplatin chemotherapy. METHODS: We investigated the whole-body distribution and radiation dosimetry of 195mPt-cisplatin in humans. Whole-body scans were obtained up to 144 h after intravenous injection of 112.4 MBq 195mPt-cisplatin in each of five subjects. Blood samples were taken at various times up to 144 h after injection. Urine was collected up to 114 h after injection for calculation of renal clearance and whole-body clearance. Time/activity curves were generated by fitting the organ-specific geometric mean counts, obtained from regions of interest, on the respective images as a function of the time after injection. OLINDA software package was applied to calculate the absorbed radiation dose for various organs. RESULTS: Most of the activity (32 ± 4%) was excreted in the urine during the first 5 h. The effective clearance half-life derived from extrapolation of the whole-body curve was 40 hours (1.7 days). On average, the highest dose was received by the kidneys (mean dose received 2.68 ± 1.5 mGy/MBq), followed by the spleen (mean dose received 1.6 ± 0.8 mGy/MBq) followed by the liver (mean dose received 1.45 ± 0.38 mGy/MBq). The estimated mean effective dose for the adult subject was 0.185 ± 0.034 mSv/MBq. CONCLUSION: 195mPt-cisplatin proved a safe radiopharmaceutical with a favourable biodistribution for early and delayed imaging of pathology above the diaphragm. The ED obtained was 0.185 ± 0.034 mSv/MBq. The highest organ dose was received by the kidneys (2.68 ± 1.5 mGy/MBq).

Production of (117m)Sn with high specific activity by cyclotron.

A method to produce (117m)Sn radionuclide using accelerator production route is described. A new method is proposed to separate the (117m)Sn. Specific activities and thick target yield for (116)Cd(α,3n)(117m)Sn reaction at E(α)=35MeV bombarding energy were determined. The estimated production yield of (117m)Sn was 37.5kBq/µAh for 13.16 mg/cm(2) natural cadmium-oxide target and 410 kBq/µAh for 11.07 mg/cm(2) highly enriched (95%) (116)CdO target. The method developed for separation of (117m)Sn from Cd using anion-exchange resin (Dowex -1×8, fluorine form, 400 mesh) can achieve 98% radiochemical yield of (117m)Sn with more than 99% radionuclidic purity. The estimated specific activity is 2.4 GBq/mg that can be reached with the used irradiation conditions.

The anti-tumour properties and biodistribution (as determined by the radiolabeled equivalent) of Au-compounds intended as potential chemotherapeutics.

The anti-tumour activity of the Au (I) phosphine complex [Au(dppe(2)]Cl was first discovered in the mid 1980s although promising results were obtained it did not pass clinical studies because of its toxicity to organs such as the liver and heart. The aim of this study was to determine whether the two novel gold compounds (MM5 and MM6), selected for this study, have higher selectivity for cancer cells with less toxicity towards normal cells than [Au(dppe)(2)]Cl, and also to determine whether they have improved bio distribution compared to [Au(dppe)(2)]Cl. The Au-compounds as potential chemotherapeutic drugs were evaluated by using radioactive tracers in the in vitro and in vivo studies. Results obtained from these experiments showed that the uptake of these experimental compounds was dependent on their octanol/water partition coefficient. However; the inhibition of cell growth did not correlate with the uptake of these compounds by the cells that were tested. In terms of the total uptake it was found that the compounds that were less lipophilic (MM5, MM6) were taken up less efficiently in cells than those that are more lipophilic. Therefore hydrophilic drugs are expected to have a limited biodistribution compared to lipophilic drugs. This might imply a more selective tumour uptake.

Metal-ion speciation in blood plasma incorporating the tetraphosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropilydenediphosphonate (APDDMP), in therapeutic radiopharmaceuticals.

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with 166Ho and 153Sm complexed to the bone seeking phosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD) and was complexed to lanthanide trivalent metal ions. This work is performed to utilise the idea that the energetic beta-particle emitter, 166 Ho, coupled with phosphonate ligands such as APD and APDDMP could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca2+, Mg2+, and Zn2+ and the trivalent lanthanides Ho3+ and Sm3+ were measured by glass electrode potentiometry at 37 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from animal tests. The 166Ho-APDDMP complex was found to have little liver or bone uptake while 153Sm-APDDMP had a moderate bone uptake. This was primarily due to the high affinity of APDDMP for Ca(II). Clinical observations could be explained by the blood plasma modelling.

Metal-ion speciation in blood plasma incorporating the bisphosphonate, 1-hydroxy-4-aminopropilydenediphosphonate (APD), in therapeutic radiopharmaceuticals.

In the quest for more effective pain palliation radiopharmaceuticals for metastatic bone cancer, this paper relates results obtained with 166Ho complexed to the bone-seeking bisphosphonate, 1-hydroxy-4-aminopropililydenediphosphonate (APD). APD is itself a bone cancer pain palliation agent and this work was therefore driven by the idea that the energetic beta-particle emitter, 166Ho, coupled with APD could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants for important blood plasma metal-ions were measured by potentiometry or polarography at 37 degrees C and I = 150 mmol dm-3. The latter technique was used for systems where precipitates formed at ligand-to-metal ratios appropriate for potentiometry. For trivalent lanthanides, neither electrochemical technique could be used. Animal tests showed that the 166Ho-APD complex was taken up primarily by the liver due to precipitation or colloid formation.