Metal-ion Speciation in Blood Plasma as a Tool in Predicting the "in vivo" Behaviour of Potential Bone-Seeking Radiopharmaceuticals

In a quest for more effective radiopharmaceuticals for palliation of pain experienced by metastatic bone cancer patients, results obtained with the therapeutic radionuclides 153 SM, 166 Ho and 117mSn complexed to bone-seeking phopsphate ligands are related. As phosphonates are known to enhance the remodelling of bone and to have the ability to act as bone cancer pain palliation agents, they were the ideal starting point of our search. Models for speciation of components in blood plasma were constructed by including the measured blood plasma metal-ions, Ca, Mg, Zn, as well as Sm. The formation constants were measured by glass electrode potentiometry or polarography, or if necessary estimated by linear free energy plots (LFER). For the blood plasma models the computer programme ECCLES was used. Using these models the biodistribution or radiopharmaceuticals in blood plasma could be evaluated and explanations found for their in vivo behaviour. Although blood plasma spectation models, based on thermodynamic considerations, only indicate in what species a radiopharmaceutical will be present in blood plasma, they were able to provide insight into in vivo behaviour of the proposed bone seeking radiopharmaceuticals and how a future radiopharmaceuticals should be designed. This approach will be illustrated at the hand of newly designed radiopharmaceuticals as well as results achieved by others.Interfaculty Reactor Institut

Biodistribution and dosimetry of 195mPt-cisplatin in normal volunteers

195mPt-cisplatin is regarded as a promising imaging agent for optimizing dosage in patients receiving cisplatin chemotherapy. We investigated the whole-body distribution and radiation dosimetry of 195mPt-cisplatin in humans. Methods: 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 wholebody 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)

Method of producing radionuclides

The invention relates to a method of producing radionuclides. According to the method, a target medium comprising at least a target nuclide material is irradiated in an irradiation zone with neutron irradiation. Radionuclides form in the target nuclide material as a result of the irradiation, and at least some of the formed radionuclides are ejected from the target nuclide material. The ejected radionuclides are then captured and collected in a carbon-based recoil capture material which does not have an empty cage structure at crystallographic level.Delft University of Technolog

Precise activity measurements of medical radionuclides using an ionization chamber: a case study with Terbium-161.

<sup>161</sup> Tb draws an increasing interest in nuclear medicine for therapeutic applications. More than 99% of the emitted gamma and X-rays of <sup>161</sup> Tb have an energy below 100 keV. Consequently, precise activity measurement of <sup>161</sup> Tb becomes inaccurate with radionuclide dose calibrators when using inappropriate containers or calibration factors to account for the attenuation of this low energy radiation. To evaluate the ionization chamber response, the sample activity must be well known. This can be performed using standards traceable to the Système International de Référence, which is briefly described as well as the method to standardize the radionuclides. In this study, the response of an ionization chamber using different container types and volumes was assessed using <sup>161</sup> Tb. The containers were filled with a standardized activity solution of <sup>161</sup> Tb and measured with a dedicated ionization chamber, providing an accurate response. The results were compared with standardized solutions of high-energy gamma-emitting radionuclides such as <sup>137</sup> Cs, <sup>60</sup> Co, <sup>133</sup> Ba and <sup>57</sup> Co. For the glass vial type with an irregular glass thickness, the <sup>161</sup> Tb measurements gave a deviation of 4.5% between two vials of the same type. The other glass vial types have a much more regular thickness and no discrepancy was observed in the response of the ionization chamber for these type of vials. Measurements with a plastic Eppendorf tube showed stable response, with greater sensitivity than the glass vials. Ionization chamber measurements for low-energy gamma emitters (< 100 keV), show deviation depending on the container type used. Therefore, a careful selection of the container type must be done for activity assessment of <sup>161</sup> Tb using radionuclide dose calibrators. In conclusion, it was highlighted that appropriate calibration factors must be used for each container geometry when measuring <sup>161</sup> Tb and, more generally, for low-energy gamma emitters

First-in-Humans Application of Tb-161:A Feasibility Study Using Tb-161-DOTATOC

(161)Tb has decay properties similar to those of (177)Lu but, additionally, emits a substantial number of conversion and Auger electrons. The aim of this study was to apply (161)Tb in a clinical setting and to investigate the feasibility of visualizing the physiologic and tumor biodistributions of (161)Tb-DOTATOC. Methods: (161)Tb was shipped from Paul Scherrer Institute, Villigen-PSI, Switzerland, to Zentralklinik Bad Berka, Bad Berka, Germany, where it was used for the radiolabeling of DOTATOC. In 2 separate studies, 596 and 1,300 MBq of (161)Tb-DOTATOC were administered to a 35-y-old male patient with a metastatic, well-differentiated, nonfunctional malignant paraganglioma and a 70-y-old male patient with a metastatic, functional neuroendocrine neoplasm of the pancreatic tail, respectively. Whole-body planar γ-scintigraphy images were acquired over a period of several days for dosimetry calculations. SPECT/CT images were reconstructed using a recently established protocol and visually analyzed. Patients were observed for adverse events after the application of (161)Tb-DOTATOC. Results: The radiolabeling of DOTATOC with (161)Tb was readily achieved with a high radiochemical purity suitable for patient application. Planar images and dosimetry provided the expected time-dependent biodistribution of (161)Tb-DOTATOC in the liver, kidneys, spleen, and urinary bladder. SPECT/CT images were of high quality and visualized even small metastases in bones and liver. The application of (161)Tb-DOTATOC was well tolerated, and no related adverse events were reported. Conclusion: This study demonstrated the feasibility of imaging even small metastases after the injection of relatively low activities of (161)Tb-DOTATOC using γ-scintigraphy and SPECT/CT. On the basis of this essential first step in translating (161)Tb to clinics, further efforts will be directed toward the application of (161)Tb for therapeutic purposes