9 research outputs found
Cyclotron production of 43Sc for PET imaging
Recently, significant interest in 44Sc as a tracer for positron emission tomography (PET) imaging has been observed. Unfortunately, the co-emission by 44Sc of high-energy γ rays (Eγ = 1157, 1499 keV) causes a dangerous increase of the radiation dose to the patients and clinical staff. However, it is possible to produce another radionuclide of scandium—43Sc—having properties similar to 44Sc but is characterized by much lower energy of the concurrent gamma emissions. This work presents the production route of 43Sc by α irradiation of natural calcium, its separation and purification processes, and the labeling of [DOTA,Tyr3] octreotate (DOTATATE) bioconjugate. Methods: Natural CaCO3 and enriched [40Ca]CaCO3 were irradiated with alpha particles for 1 h in an energy range of 14.8–30 MeV at a beam current of 0.5 or 0.25 μA. In order to find the optimum method for the separation of 43Sc from irradiated calcium targets, three processes previously developed for 44Sc were tested. Radiolabeling experiments were performed with DOTATATE radiobioconjugate, and the stability of the obtained 43Sc-DOTATATE was tested in human serum. Results: Studies of natCaCO3 target irradiation by alpha particles show that the optimum alpha particle energies are in the range of 24–27 MeV, giving 102 MBq/μA/h of 43Sc radioactivity which creates the opportunity to produce several GBq of 43Sc. The separation experiments performed indicate that, as with 44Sc, due to the simplicity of the operations and because of the chemical purity of the 43Sc obtained, the best separation process is when UTEVA resin is used. The DOTATATE conjugate was labeled by the obtained 43Sc with a yield >98 % at elevated temperature. Conclusions: Tens of GBq activities of 43Sc of high radionuclidic purity can be obtainable for clinical applications by irradiation of natural calcium with an alpha beam
Separation of fission produced 106Ru from simulated high level nuclear wastes for production of brachytherapy sources
Improvement in the Safety of Use of Hand Dishwashing Liquids Through the Addition of Hydrophobic Plant Extracts
Cyclotron production of 44Sc - new tracer for PET technique
Objectives: Two isotopes of scandium, 47Sc and 44Sc, are perspective radionuclides respectively for radiotherapy and diagnostic imaging. 47Sc decays with the half-life of 3.35 days and maximum β- energy of 600 keV. It also emits low-energy γ-radiation (Eγ = 159 keV) suitable for simultaneous imaging. The other scandium radionuclide - 44Sc (t1/2 = 3.92h) is an ideal β+-emitter in PET diagnosis. It can be used instead of 68Ga, because 44Sc has longer half-life and forms stable radiobioconjugates with a structure similar to 90Y and 177Lu, what is important in planning radionuclide therapy [1]. 44Sc can be obtained as a daughter radionuclide of long-lived 44Ti (t1/2 = 60.4y) from 44Ti/44Sc generator or can be produced by nuclear reaction 44Ca (p, n) 44Sc in small cyclotrons. The aim of our work was to find optimal parameters for 44CaCO3 target irradiation in order to maximize production of 44Sc with minimal impurities of longer-lived 44mSc and development of simple chemical procedure for separation of 44Sc from the calcium target.
Methods: The irradiation of enriched 44CaCO3 Isoflex (Russia) was performed with the Scanditronix MC 40 Cyclotron Joint Research Centre (Ispra, Italy). In stack target, 2mg of enriched CaCO3 in aluminum foil envelop were used together with Cu disk as beam current monitor. The copper monitor was positioned in entrance of the stack which allowed to have an accurate measurement of the proton beam current by measuring the 44Sc activity. The stack-foil target was irradiated in aluminum capsules inserted in a holder that allowed direct water cooling from the rear and the front side.
Longer-lived 46Sc was used instead of 44Sc in the separation procedure. The CaCO3 target (10 mg) was dissolved in 1 ml of 0.1 M HCl. Next, the solution was passed through the small column filled with iminodiacetic resin Chelex-100. After adsorption of 46Sc the column was washed with 30 ml of 0.01 M HCl and the effluent containing enriched calcium was collected for further irradiations. The 46Sc was quantitatively eluted with 1 M HCl in the second 0.5 ml fraction.
Results: The 44CaCO3 target was irradiated by protons in the range of 5.5-23MeV. The analysis of several irradiations indicate that the amount of 44Sc obtained is maximal with minimal (0.16%) 44mSc impurity in the energy range of 9-10MeV. 46Sc was separated from the target on iminodiacetic resin with efficiency of more than 95%, eluted in volume of 0.5 ml. The recovery of the calcium target is nearly quantitative. The level of Ca2+ in 46Sc fraction is less than3 g/ml.
Conclusions: The low-energy irradiation of 44Ca gives opportunity to produce Ci level activities of 44Sc. The separation process proposed of 44Sc from the target is simple and fast. The 44Sc obtained can be used instead of 68Ga in PET diagnosis and planning radionuclide receptor therapy..
Research Support: This work was carried out as a part of the project of the Ministry of Science and Higher Education of Poland DWM/N166/COST/2007 and COST Action D38.
References: [1] A.Majkowska, A.Bilewicz, J.Inorg.Biochem. 105 (2011) 313–320.JRC.I.4-Nanobioscience
Organic Cation Transporter-Mediated Accumulation of Quinolinium Salts in the LV Myocardium of Rodents
Purpose: Quaternary ammonium salts have demonstrated marked accumulation in the left ventricular (LV) myocardium of rodents and swine. To investigate the mechanism underlying this uptake, the present study examined the interaction of [F-18]fluoroethylquinolinium ([F-18]FEtQ) with the family of organic cation transporters (OCTs). Procedures: The cellular uptake of [F-18]FEtQ into HEK293 cells, expressing human OCT1, -2, or -3 (HEK293-hOCT), and its inhibition by corticosterone was evaluated in vitro. The inhibitory effect of decynium 22 (D 22) in vivo was also studied, using PET/CT of HEK293-hOCT tumor-bearing mice. Furthermore, the distribution kinetics of [F-18]FEtQ were determined in rats, with and without pre-administration of corticosterone, and following administration to a non-human primate (NHP). Results: The accumulation of [F-18]FEtQ in HEK293-hOCT cells was 15-20-fold higher than in control cells and could be inhibited by corticosterone. in vivo, the uptake of [F-18]FEtQ in the LV myocardium of corticosterone-treated rats was significantly reduced compared to that of untreated animals. Similarly, following administration of D 22 to HEK293-hOCT tumor-bearing mice, the peak tumor uptake of [F-18] FEtQ was reduced by 40-45 % compared to baseline. Contrary to the distinct accumulation of [F-18]FEtQ in the LV myocardium of rats, no cardiac uptake was observed following its administration to a NHP. Conclusions: The quinolinium salt derivative [F-18]FEtQ interacts with the family of OCTs, and this interaction could account, at least in part, for the increased uptake in the LV myocardium of rodents. Nonetheless, its low affinity for hOCT3 and the results of PET/CT imaging in a NHP indicate a limited clinical applicability as a radiopharmaceutical for cardiac and/or OCT imaging
Simple and fast procedure of labelling DOTATATE with 86Y and 44Sc.
Beta+ emitting 44Sc (T1/2 = 3.92 h) and 86Y (T1/2 = 14.87 h) are prospective radionuclides for diagnostic imaging using the PET technique. They can be produced in medical cyclotrons with the (p,n) reaction on enriched 44Ca/86SrCO3 targets and 44Sc additionally from 44Ti/44Sc generators. The main advantages of these radionuclides are the relatively long half-life and the formation of the “matched pair” with therapeutic radioisotopes, 47Sc and 90Y, respectively. A simple and fast procedure is presented for labeling of DOTATATE with 44Sc and 86Y. DOTATATE was used as a model molecule and results can be transferred to labelling of other DOTA-bioconjugates. The proposed method can be applicable for PET imaging, but clinical investigation is necessary.JRC.I.4-Nanobioscience
Multiparametric Evaluation of Post-MI Small Animal Models Using Metabolic ([18F]FDG) and Perfusion-Based (SYN1) Heart Viability Tracers
Cardiovascular diseases (CVD), with myocardial infarction (MI) being one of the crucial components, wreak havoc in developed countries. Advanced imaging technologies are required to obtain quick and widely available diagnostic data. This paper describes a multimodal approach to in vivo perfusion imaging using the novel SYN1 tracer based on the fluorine-18 isotope. The NOD-SCID mice were injected intravenously with SYN1 or [18F] fluorodeoxyglucose ([18F]-FDG) radiotracers after induction of the MI. In all studies, the positron emission tomography–computed tomography (PET/CT) technique was used. To obtain hemodynamic data, mice were subjected to magnetic resonance imaging (MRI). Finally, the biodistribution of the SYN1 compound was performed using Wistar rat model. SYN1 showed normal accumulation in mouse and rat hearts, and MI hearts correctly indicated impaired cardiac segments when compared to [18F]-FDG uptake. In vivo PET/CT and MRI studies showed statistical convergence in terms of the size of the necrotic zone and cardiac function. This was further supported with RNAseq molecular analyses to correlate the candidate function genes’ expression, with Serpinb1c, Tnc and Nupr1, with Trem2 and Aldolase B functional correlations showing statistical significance in both SYN1 and [18F]-FDG. Our manuscript presents a new fluorine-18-based perfusion radiotracer for PET/CT imaging that may have importance in clinical applications. Future research should focus on confirmation of the data elucidated here to prepare SYN1 for first-in-human trials