Radiopharmaceuticals Research Articles

Radiopharmaceuticals Based on Alpha Emitters: Preparation, Properties, and Application

In this review, the problems of the development of radiopharmaceuticals (RPs) based on alphaemitting radionuclides are discussed. The prospects of application of the radionuclides 227Th, 225Ac, 223Ra, 213Bi, 212Pb/212Bi, 212Bi, 211At, and 149Tb are estimated in the aspect of their physicochemical properties, such as half-life, properties of daughter radionuclides, and complexing ability. The methods used for the production of radionuclides and their industrial availability are considered. Some examples of radionuclide complexes with ligands and nanoparticles for targeted delivery are presented. The results of medical trials for RPs based on alpha emitters are given.

Clinical aspects of radiolabeled aptamers in diagnostic nuclear medicine: A new class of targeted radiopharmaceuticals.

Targeted radiopharmaceuticals offer the possibility of improved imaging with reduced side effects. Up to now, a variety of biological receptors such as aptamers have been successfully radiolabeled and applied to diagnostic imaging of cancers. The concept of using radio-labeled aptamers for binding to their targets has stimulated an immense body of research in diagnostic nuclear medicine. These biological recognition elements are single-stranded oligonucleotides that interact with their target molecules with high affinity and specificity in unique three-dimensional structures. Because of their high affinity and specificity, the receptor-binding aptamers labeled with gamma emitters such as 99mTc, 64Cu, 111In, 18F and 67Ga can facilitate the visualization of receptor-expressing tissues noninvasively. Compared to the antibody-based radiopharmaceuticals, the radiolabeled aptamers provide a number of advantages for clinical diagnostics including high stability, low cost, and ease of production and modification, low immunogenicity and, especially, superior tissue penetration because of their smaller size. In this review, we present recent progresses and challenges in aptamer-based diagnostic radiopharmaceuticals and highlight some representative applications of aptamers in nuclear medicine.

Jörg Steinbach-A highly motivated radiopharmaceutical scientist.

Jörg Steinbach-A highly motivated radiopharmaceutical scientist.

Bone-Targeting Radiopharmaceuticals as Monotherapy or Combined With Chemotherapy in Patients With Castration-Resistant Prostate Cancer Metastatic to Bone

In patients with metastatic castration-resistant prostate cancer, bone is the most common site for metastases. Because of their osteoblastic character, these lesions are very suitable for treatment with bone-seeking radiopharmaceuticals (RPs). Nowadays, radium-223-chloride is the only RP with a proven benefit in overall survival, whereas the β-emitting RPs are used for pain palliation. In the past, many trials that investigated RPs alone, or in combination with chemotherapy have been performed. Because of different designs, characteristics of included patients, and chemotherapeutical and RP regimens, interpretation of the promising data and positioning of RPs in the treatment of metastatic prostate cancer has become difficult. In this review, we provide an overview of the existing data per RP with a focus on the different RPs in combination with chemotherapy. Furthermore, we aim to clarify the benefits on pain response and quality of life. Finally, we focus on the optimal timing and use of biomarkers in the treatment of patients with castration-resistant prostate cancer with RPs.

Thrombolytic and Anticoagulant Therapy for Pulmonary Embolism with High and Intermendiate Risk of Early Death. Part 3. An Effect on Pulmonary Perfusion with High and Intermediate Risk of Early Death

Background The advantage of thrombolytic therapy (TLT) over anticoagulant therapy(ACT) in patients with a high risk of early death (hemodynamic disorders) in acute pulmonary embolism is considered proven. But the advantage of thrombolytic therapy over anticoagulant therapy remains uncertain in patients with an intermediate risk. Perfusion lung scintigraphy helps provide a quantitative comparison of changes in pulmonary blood flow with the use of different treatment methods in subgroups of high and intermediate risk of an adverse outcome.The aim of study is to compare the effectiveness of thrombolytic and anticoagulant therapy in the treatment of acute pulmonary embolism in patients with a high and intermediate risk of early death in terms of the dynamics of pulmonary perfusion disorders.Study design: a prospective non-randomized study. The introduction of a thrombolytic was cosidered as intervention. The comparison group consisted of patients who received an anticoagulant. Thrombolysis in patients with intermediate risk was indicated in the absence of a potential threat of hemorrhagic complications, a deficit of pulmonary perfusion above 40%, a high level of pulmonary hypertension and a high probability of cardiac decompensation. The method of comparison was the quantitative result of pulmonary perfusion deficiency.Description of the method Radionuclide and CT studies were carried out using a hybrid system SPECT/CT Discovery NM/CT 670 (GE, USA): the perfusion was evaluated with 80–120 MBq of 99mTc macrotech radiopharmaceutical (RP) (effective equivalent dose of 0.8–1.3 mSv), CT angiography was performed with 70–100 ml of radiopaque substance Visipaque (effective equivalent dose of irradiation 9.4–10.3 mSv). The accumulation deficit of an area equal to a segment was counted as a perfusion deficiency of 5% (subsegmental 2.5%), inferior lobe — 25%, an area equal to the right lung — 55%, the left lung — 45%.Characteristics of the sample In a sample of 503 patients who received treatment at the Intensive Care Unit for Surgical Patients of the N.V. Sklifosovsky Institute for Emergency Medicine from 2011 to 2016, the overall mortality rate was 14.7% (95% CI 11.7; 18.1) (74/503); anticoagulation therapy — 17.8% (95% CI 13.5; 22.8) (50/281); thrombolytic therapy — 10.8% (95% CI 7.1; 15.6) (24/222); p=0.031, Fisher’s test, P=0.60. At a high risk of death, the mortality rate in the thrombolytic therapy group was 30.2% (19/63) versus 47.1% (32/68) in the anticoagulant therapy group; p=0.051, the Fisher’s test; P=0.51. At an intermediate risk, it was 3.2% (5/158) and 8.4% (8/214); p=0.049, the Fisher’s test, P=0.54. Changes in pulmonary perfusion deficiency as a result of treatment were performed in 169 patients who promptly underwent a primary and repeated dynamic scintigraphic study: 127 patients after thrombolysis (of which 38 patients had a high risk and 88 had an intermediate risk) and 42 patients who were treated with an anticoagulant (5 — high risk, 37 — intermediate risk). The groups did not differ in age and gender composition: the mean age was 59±16; Me 61 (49; 71) and 57±14 years; Me 58 (43; 67), respectively; p=0.50 (Mann–Whitney test); men/women: 50/77 and 12/30; p=0.27, the Fisher’s test. The groups differed in the presence of cancer: in the ACT group, the proportion of patients with cancer was 21.4% (9/42), and in the TLT group it was 4.7% (6/127), p=0.003, the Fisher’s test, P=0.85.Results Patients of high and intermediate risk, who received thrombolysis, were in a significantly more serious condition in terms of baseline characteristics. Both methods of treatment were effective. In high-risk patients, perfusion deficiency regressed: from 57±10% (Me 60 (50; 65)) to 31±15% (Me 30 (20; 40)), p<0.00001 (Wilcoxon test), Es=2.08, P=1.00 after TLT; from 38±9% (Me 40 (35; 40)) to 14±8% (Me 10 (10; 20)), p=0.043 (Wilcoxon test), Es=2.72, P=0.93 after ACT. In patients with intermediate risk, perfusion deficiency regressed: from 48±9% (Me 50 (40, 55)) to 24±13% (Me 20 (15; 30)), p<0.00001 (Wilcoxon test) after TLT; from 38±11% (Me 40 (30; 45)) to 24±15% (Me 15 (15; 30)), p=0.00003 (Wilcoxon test) after ACT. The effect size for TLT was Es=2.16, for ACT Es=1.13. The power of the study was P=1.00 and P=0.99.Conclusion Thrombolytic therapy was more effective in restoring pulmonary perfusion compared to anticoagulants in patients with an intermediate risk of early death: the effect of thrombolysis was greater than that of anticoagulant therapy (Es=2.16 and Es=1.13). The absence of the effect of restoring pulmonary perfusion during thrombolysis was noted less frequently compared to the results of anticoagulant therapy: in 5.5% (95% CI 2.2–11.0) vs. 19.0% (95% CI 8.6–34.1).

Функціональний стан нирок у дітей, що перенесли гостре пошкодження нирок, в катамнезі спостереження.

Гостре пошкодження нирок (ГПН) у дітей має поліетіологічну структуру, особливості перебігу залежні від віку захворювання і високий ризик розвитку хронічної хвороби нирок (ХХН) в катамнезі.
 Метою дослідження стало вивчення функціонального стану нирок у дітей, що перенесли ГПН, у віддалених термінах.
 Матеріали та методи. Було ретроспективно проаналізовано функціональний стан нирок (швидкість клубкової фільтрації (ШКФ)за Шварцом, рівень паратіреоідного гормону (ПТГ), альбумінурії (АУ), динамічної і статичної реносцинтиграфіі(РСГ)) за даними 60 історій хвороб дітей від 1 до 18 років, що перенесли ГПН протягом 2000-2016 р.р.
 Результати. Протягом першого року спостереження у 61,5% хворих зберігалась азотемія,, уповільнення ШКФ та високий рівень АУ. Подальше спостереження за цією групою хворих виявило тенденцію нормалізації рівнів креатиніну, сечовини, ШКФ, але зростання рівнів АУ. В динаміці спостереження від 5 до 15 років, визначено, що у 13,3% пацієнтів ШКФ становила від 90 до 85 мл/мін, а у 36,7% - від 85 до 30 мл/мін. У 46,7% дітей при не змінених показниках креатиніну і ШКФ, відмічено зростання рівню альбумінурії від 45 до 601 мг/добу. За період спостереження, від 15 років і більше, повністю одужало 53,3% дитини, у 31,6% хворих констатована хронічна ниркова недостатність (ХНН), а у 30,0% спостерігалось одужання з дефектом - стійке зниження функції з наявними маркерами пошкодження нирок.
 Висновки. Гостре пошкодження нирок частіше зустрічалось серед дітей перших 3 років життя, переважно у хлопчиків. Етіологічним чинником виникнення захворювання був гемолітико-уремічний синдром на фоні гострої кишкової інфекції. Повне одужання документоване у 20,0% реконвалесцентів ГПН, у 30,0% констатовано персистенцію маркерів пошкодження нирки з відновленням функції, а у 18,3% значне, стійке зниження функції нирок. Багатоцільове сцинтиграфічне дослідження з радіофірмпрепаратами різного типу виведення виявило ознаки порушення канальцевих та гломерулярних функцій за 7-8 років до появи лабораторних змін.

Technetium and Rhenium Schiff Base Compounds for Nuclear Medicine: Syntheses of Rhenium Analogues to 99mTc-Furifosmin.

Rhenium, the third-row congener of technetium, is often used to develop the macroscopic chemistry of potential 99mTc diagnostic radiopharmaceuticals. The rhenium analogues to 99mTc-furifosmin are being developed for potential radiotherapy of multidrug-resistant tumors. Complexes of the form trans-[MIII(PR3)2(N2O2-Schiff base)]+ are of interest for the potential imaging and treatment of multidrug-resistant tumors. Reaction of the tetradentate Schiff ligand 4,4'-[(1 E,1' E)-[ethane-1,2-diylbis(azanylylidene)]bis(methanylylidene)]bis(2,2,5,5-tetramethyl-2,5-dihydrofuran-3-ol) (tmf2enH2) with the M(V) starting materials ( nBu4N)[TcOCl4] and ( nBu4N)[ReOCl4] gave the monomeric products trans-[TcOCl(tmf2en)] and trans-[ReOCl(tmf2en)], respectively. Reduction of in situ formed trans-[ReOCl(tmf2en)] by various tertiary phosphines yielded disubstitued Re(III) products of the general type trans-[ReIII(PR3)2(tmf2en)]+. The rhenium(III) compounds were found to be water-soluble and stable in aqueous solution. Reversible ReIII/ReIV and ReIII/ReII redox processes were observed at about 0.8-0.9 and -0.65 to -0.8 V, respectively, for each of the rhenium(III) species. Reaction of in situ formed trans-TcOCl(tmf2en) with triethylphosphine yielded the reduced, disubstituted trans-[Tc(PEt3)2(tmf2en)]PF6. A reversible TcIII/TcII redox couple was observed for the technetium(III) species, about 200 mV less negative than their rhenium(III) analogues, in addition to an irreversible TcIII/TcIV process. All compounds were characterized using conventional spectroscopic techniques, single-crystal X-ray crystallography, and cyclic voltammetry.

The development of technology of Fludeoxyglucose (18F) for injection, laboratory analysis methods

18F-Fluorodeoxyglucose has optimal characteristics for use in nuclear medicine and is a priority among radiopharmaceuticals for the diagnosis of cancer by positron emission tomography (PET). 18F-Fluorodeoxyglucose has the longest half-life with the lowest energy of radiation, it allows to obtain PET images of high contrast at low dose loading on the patient. Low energy positron radiation provides high spatial resolution of PET images. However, the half-life of 18F-Fluorodeoxyglucose is large enough to allow the transportation of radiopharmaceuticals from the centralized production site to diagnostic centers with PET scanners (the so-called PET satellite concept), and to extend the time limits of PET research and synthesis of radiopharmaceuticals [1].
 The study is the development of technology and quality control methods to ensure quality at all stages of the production of radiopharmaceuticals 18F-Fluorodeoxyglucose, injection.
 There was justified 18F-Fluorodeoxyglucose production technology and quality control at all stages of production, based on complex research in the department producing radiopharmaceuticals Ukrainian Center of radiosurgery consisting Clinical Hospital «Feofaniya».
 Object of study – 18F-Fluorodeoxyglucose, injection, injection is used in nuclear medicine for PET diagnosis of cancer.
 We used the biopharmaceutical and pharmaceutical methods.
 For the first time based pharmaceutical research was the rational technology of diagnostic radiopharmaceuticals 18F-Fluorodeoxyglucose, injection for use in PET diagnosis of cancer patients. Methods of controlling drug 18F-Fluorodeoxyglucose, injection according monographs of the State Pharmacopoeia of Ukraine. On the basis of the analysis developed by established methods of control performance specifications and shelf life of radiopharmaceuticals 18F-Fluorodeoxyglucose, injection.

THROMBOLYTIC AND ANTICOAGULANT THERAPY FOR PULMONARY EMBOLISM: AN EFFECT ON PULMONARY PERFUSION (PART 2)

Background.Perfusion scintigraphy reveals perfusion defects in the occlusion of pulmonary vessels of any caliber and makes it possible to quantify pulmonary blood flow disorders, which allows the method to be used for the comparison of the thrombolytic and anticoagulant therapy efficacy in patients with acute pulmonary embolism.Aim of study .To compare the efficacy of thrombolytic and anticoagulant therapy in the treatment of acute pulmonary embolism in the dynamics of pulmonary perfusion disorders.Study Design.A prospective non-randomized study. The quantitative result of pulmonary perfusion deficiency obtained during perfusion scintigraphy was compared in patients with pulmonary embolism treated with thrombolytics or anticoagulants before treatment and in dynamics. The dynamics was evaluated the next day after administration of thrombolytics and on day 4–5 after initiating anticoagulant therapy. Preliminary analysis of these parameters in the group with anticoagulant therapy a day after the start of administration (by analogy with TLT) revealed no statistically significant differences.Description of the method.Radionuclide and CT studies were performed on a hybrid system SPECT/CT “Discovery NM/CT 670” (GE, USA): perfusion was evaluated with 80–120 MBq of Macrotech 99mTc radiopharmaceutical (RP), CT angiography was performed with 70-100 ml of radiopaque substance “Visipaque.” To determine the total perfusion deficiency, each defect of accumulation with an area equal to the segment was taken as a perfusion deficiency of 5% (subsegmental — 2.5%), equal to the lower lobe — 25%, an area equal to the right lung — 55%, the left lung — 45%. Characteristics of the sample.The perfusion scintigraphy was performed in 381 cases out of 503 patients with a diagnosis of pulmonary embolism of high/intermediate risk of early death, treated in the Intensive Care Unit for Surgical Patients from 2011 to 2016. In 166 cases out of 381, thrombolysis was performed; in 215 cases, an anticoagulant was prescribed. The groups did not differ in age and gender composition: 60±16 years; Me 61 (50; 71) and 62±15 years; Me 63 (53; 74); p=0.22, Mann-Whitney test; men/women: 73/93 and 89/126; p=0.68, the Fisher test.Results of the study.In 96.1% (366/381), perfusion disorders were observed in both lungs; in 3.9% (15/381) there was a unilateral lesion. The comparison of the treatment efficacy was conducted in 169 patients: in 127 cases the next day after introduction of a thrombolytic and in 42 cases on day 4–5 of anticoagulant therapy. In the group with thrombolysis, the initial perfusion deficiency was statistically significantly higher than in the anticoagulant group: 50±10%; Me 50 (40; 60) vs. 39±10; Me 40 (30; 45); p<0.00001, the Mann–Whitney test. The level of pulmonary hypertension was also higher: the systolic pressure in the pulmonary artery was 56±17 Me 54 (45, 68) versus 40±24 Me 40 (22; 56); p<0.00001, the Mann–Whitney test. As a result of treatment, the perfusion deficiency statistically significantly decreased in both groups: in the group with TLT from 50±10%, Me 50 (40; 60) to 26±14%; Me 25 (15; 35); p<0.00000.1, Wilcoxon test; and in the treatment with anticoagulant it decreased from 39±10%, Me 40 (30; 45) to 23±15%; Me 15 (15; 30); p<0.0001, Wilcoxon test. In the TLT group, the perfusion disorders regression was stronger compared to ACT and was registered the next day after administration of a thrombolytic: the standardized effect Es=2.0 and Es=1.2. In the treatment with anticoagulants, statistically significant differences were detected only on day 4–5 from the beginning of its administration. The study power for both groups was 1.00. After thrombolysis the systolic pressure in the pulmonary artery decreased statistically significantly within the next 24 hours: from 56±17 mmHg, Me 54 (45, 68) to 36±14 mmHg, Me 35 (25; 43); p=0.0002, Wilcoxon test; Es=1.3; P=1.00. With anticoagulant treatment, no statistically significant changes in pulmonary arterial pressure occurred 4-5 days after the initiation of treatment: 40±24 mmHg, Me 40 (22; 56) and 50±31 mm Hg, Me 48 (30; 58) ); p=0.72, Wilcoxon test.Conclusion.The advantage of thrombolysis over anticoagulant therapy was the ability to improve pulmonary blood flow, reduce pulmonary hypertension, and stabilize the patients’ condition quickly. Anticoagulant therapy did not allow this effect to be achieved in a short time: the statistically significant reduction in pulmonary perfusion deficiency occurred only on day 4–5 of treatment and was less significant; the statistically significant regression of pulmonary hypertension did not occur at that time.

Radio-pharmaceuticals for cancer treatment: are they ready for prime time yet?

Radio-pharmaceuticals for cancer treatment: are they ready for prime time yet?

A Monte Carlo model for the internal dosimetry of choroid plexuses in nuclear medicine procedures

Choroid plexuses are vascular structures located in the brain ventricles, showing specific uptake of some diagnostic and therapeutic radiopharmaceuticals currently under clinical investigation, such as integrin-binding arginine-glycine-aspartic acid (RGD) peptides. No specific geometry for choroid plexuses has been implemented in commercially available software for internal dosimetry.The aims of the present study were to assess the dependence of absorbed dose to the choroid plexuses on the organ geometry implemented in Monte Carlo simulations, and to propose an analytical model for the internal dosimetry of these structures for 18F, 64Cu, 67Cu, 68Ga, 90Y, 131I and 177Lu nuclides. A GAMOS Monte Carlo simulation based on direct organ segmentation was taken as the gold standard to validate a second simulation based on a simplified geometrical model of the choroid plexuses. Both simulations were compared with the OLINDA/EXM sphere model.The gold standard and the simplified geometrical model gave similar dosimetry results (dose difference < 3.5%), indicating that the latter can be considered as a satisfactory approximation of the real geometry. In contrast, the sphere model systematically overestimated the absorbed dose compared to both Monte Carlo models (range: 4–50% dose difference), depending on the isotope energy and organ mass. Therefore, the simplified geometric model was adopted to introduce an analytical approach for choroid plexuses dosimetry in the mass range 2–16 g. The proposed model enables the estimation of the choroid plexuses dose by a simple bi-parametric function, once the organ mass and the residence time of the radiopharmaceutical under investigation are provided.

Murine-specific Internal Dosimetry for Preclinical Investigations of Imaging and Therapeutic Agents.

There is a growing need to estimate the absorbed dose to small animals from preclinical investigations involving diagnostic and therapeutic radiopharmaceuticals. This paper introduces a Monte Carlo-based dosimetry platform called RAPID, which is capable of calculating murine-specific three-dimensional (3D) dose distributions. A comparison is performed between absorbed doses calculated with RAPID and absorbed doses calculated in a commonly used reference mouse phantom called MOBY. Four test mice containing different xenografts underwent serial PET/CT imaging using a novel diagnostic therapy (theranostic) agent NM404, which can be labeled with I for imaging or I for therapy. Using the PET/CT data, 3D dose distributions from I-NM404 were calculated in the mice using RAPID. Mean organ doses in these four test mice were compared to mean organ doses derived by using two previously published I S-values datasets in MOBY. In addition, mean tumor doses calculated in RAPID were compared to mean organ doses derived from unit density spheres. Large differences were identified between mean organ doses calculated in the test mice using RAPID and those derived in the MOBY phantom. Mean absorbed dose percent errors in organs ranged between 0.3% and 333%. Overall, mass scaling improved agreement between MOBY phantom calculations and RAPID, where percent errors were all less than 26%, with the exception of the lung in which percent errors reached values of 48%. Percent errors in mean tumor doses in the test mice and unit density spheres were less pronounced but still ranged between 8% and 23%. This work demonstrates the limitations of using pre-computed S-values in computational phantoms to predict organ doses in small animals from theranostic procedures. RAPID can generate accurate 3D dose distributions in small animals and in turn offer much greater insight on the ability of a given theranostic agent to image and treat diseases.

SOME PERSPECTIVE RADIONUCLIDES IN THE NUCLEAR MEDICINE OF KAZAKHSTAN

It is necessary to replenish the kit of the domestic generator 99mTc with new reagents, which expand the possibilities of radionuclide examination of organs and systems. It should be possible to release an ideal diagnostic pair for therapeutic radiopharmaceuticals, such as 123I for less affordable 131I. Establishing the production and cardiomyotropic and parathyroid tropic radiopharmaceutical 201Tl is important. Scintigraphy is one of the most informative imaging techniques. 68Ge/68Ga generator in accordance with the term of operation for two years, provides cancer specific pharmaceutical to oncological clinics, which is an alternative to expensive cyclotron radionuclides.

Perspective on How the FDA Should Review Diagnostic Radiopharmaceuticals.

See the associated article on page [868][1]. This article provides readers with some background on concerns raised by Dr. Marcus about the evaluation of radiopharmaceuticals in this issue of The Journal of Nuclear Medicine ([1][2]). In 1975, the U.S. Food and Drug Administration (FDA) removed the

Robust high-yield ~1 TBq production of cyclotron based sodium [99mTc]pertechnetate

This paper presents the irradiation and processing of high-current 100Mo targets at the University of Alberta (UofA) in a GMP compliant setting. For purpose of comparison with a second production facility, additional studies at Centre Hospitalier Universitaire de Sherbrooke (CHUS) are also described. IntroductionMore than 70% of today's diagnostic radiopharmaceuticals are based on 99mTc, however the conventional supply chain for obtaining 99mTc is fragile. The aim of this work was to demonstrate reliable high yield production and processing of 99mTc with medium-energy, high-current, cyclotrons. MethodsWe used two cyclotrons (TR-24, Advanced Cyclotron Systems, Inc) for irradiations with 22 MeV or 24 MeV incident energy and 400 μA current up to a maximum of 6 h. The irradiated 100Mo was dissolved using peroxide, basified using ammonium carbonate, and purified using a PEG-based solid phase extraction technique. ResultsHigh-yield productions with 22 MeV (400 μA, 6 h) yielded an average isolated [99mTc]TcO4− yield of 878 GBq ± 99 GBq (23.7 Ci ± 2.7 Ci) decay corrected to EOB, n = 8 (isolated saturation yield: 4.36 ± 0.49 GBq/μA). Irradiations with 24 MeV (400 μA, 6 h) resulted in an average isolated [99mTc]TcO4− yield of 993 GBq ± 100 GBq (26.8 Ci ± 2.7 Ci) decay corrected to EOB, n = 7 (isolated saturation yield: 4.97 ± 0.50 GBq/μA). These yields corresponds to 600–700 GBq (16–19 Ci) of [99mTc]TcO4− at release (i.e. 3 hour post-EOB). For all tested batches, the QC results were within the recently published specifications in the European Pharmacopoeia. ConclusionReliable near-TBq production yields for 99mTc can be obtained using medium-energy cyclotrons. Advances in knowledge and implications for patient careThis work presents evidence that medium-energy high-current cyclotrons can provide high yields of [99mTc]TcO4− with radionuclidic impurities levels within the specifications of the existing European Pharmacopoeia monograph, indicating that this technology can have a share in the future 99mTc supply market.

Cerenkov luminescence excited fluorescence tomography based on rare earth nanoparticles

Objective Using Cerenkov radiation energy transfer (CRET) effect of rare earth nanoparticles (RENPs) to enhance and convert Cerenkov luminescence into Cerenkov luminescence excited fluorescence, and to compare the accuracy of Cerenkov luminescence tomography (CLT) and Cerenkov luminescence excited fluorescence tomography (CLFT). Methods 68Ga (0.74 MBq) was used to respectively excite Y2O3∶Eu3+ , Er2O3 and Eu2O3 (10 mg/ml). Various radioactivities of 68Ga (3.70, 1.85, 0.92, 0.46, 0.23 MBq) were used to respectively excite Y2O3∶Eu3+ with a fixed concentration (10 mg/ml). A fixed radioactivity of 68Ga (3.70 MBq) was used to excite Y2O3∶Eu3+ with different concentrations (10.0, 5.0, 2.5, 1.2, 0.6 mg/ml) in order to find the relationships between the optical intensity and the radioactivity of 68Ga or the concentration of Y2O3∶Eu3+ . Polyethylene tubes containing 68Ga (0.74 MBq) and 68Ga (0.74 MBq) + Y2O3∶Eu3+ (1 mg) were respectively implanted into two nude mice, then PET/CT and optical imaging were acquired. Three-dimensional reconstruction was proceeded. One-way analysis of variance, two-sample t test, linear correlation analysis were used for data analysis. Results Y2O3∶Eu3+ could significantly and stably enhance the Cerenkov optical signal (F=53.35, q=17.03, P<0.001). The enhanced optical signal intensity had linear relationships with the radioactivity of 68Ga or the concentration of Y2O3∶Eu3+ (r values: 0.99 and 0.93). Three-dimensional reconstruction result showed that CLFT had significantly higher similarity than CLT (0.43±0.14 vs 0.16±0.06, t=5.090, P<0.05). Conclusion CLFT could reflect the distribution of radiopharmaceuticals more precisely than CLT, and therefore might have potential in biologic optical imaging. Key words: Lanthanoid series elements; Nanoparticles; Optical imaging; Cerenkov radiation

Возможности использования «Натрия фторида, 18f» при неопухолевых поражениях костной ткани (экспериментальное исследование)

Purpose: To study the possibility of using radiopharmaceutical (RPH) Sodium fluoride, 18F (Na18F) in order to identify the characteristics and dynamics of the development process for a number of non-neoplastic lesions in bone tissue such as fractures and osteoporosis in experimental animals by the method of positron emission tomography (PET).&#x0D; Material and methods: Two experimental models of pathology of bone tissue in rats were used: fracture and osteoporosis.&#x0D; The model of osteoporosis was created by intraperitoneal introduction of hydrocortisone during 3 weeks. The study was conducted in 22 days from the onset of the agent introduction. In areas of the chest and sacral sections of the spinal cord in experimental and intact animals we detected the value of uptake of Na18F, as well as indices of tissue density with data of X-ray CT.&#x0D; In the model of fracture of bones injury struck in the pre-anesthetized rats in the region of the shin. Animals were examined starting from the 3rd day up to the 30th day after the fracture by PET and PET/CT. We detected the value of uptake, the dynamics of Na18F accumulation, as well as indices of densitometry and signs of callus formation with CT examination.&#x0D; Results: In rats with osteoporosis compared with intact animals observed a 2,5-fold decrease of the bone tissue density in X-ray, whereas the level of metabolic activity in the bones of the PET scan with Na18F was 5.6 times lower than in healthy rats. Therefore, differences in the level of capture of the radiopharmaceutical in PET were significantly more important compared to the ratio of the values of the X-ray of the bone tissue density, determined by CT. &#x0D; In experiments with shin fracture was noted hyperfixation and increasing rate of Na18F accumulation on PET-scans since the 9th and 30th day from the start of the experiment. It reflects a process of enhancing the metabolism in the injured area. At the same time, a significant increase of densitometric density and visualisation of callus formation in the fracture by CT were detected 3 weeks later, – only by the 30th day after trauma.&#x0D; Conclusion: The use of Na18F in positron-emission tomography enables to diagnose more early and accurate the nature (osteoporosis) and intensity of processes of the restoration (fracture) in the injured bone tissue as compared to results of computed tomography.

Bone and calcium metabolism associated with malignancy. Bone management of prostate cancer in the novel anti-androgen era.

Androgen deprivation therapy(ADT)is a standard systemic therapy for prostate cancer. ADT induces bone loss(ADTIBL)and muscle loss(sarcopenia)leading to falls and farctures. There are 2 aims in bone management of prostate cancer:one is to prevent fragility fractures in patients without bone metastasis and the other is to prevent symptomatic skeletal events(SSE)which are pathologic fractures, spinal compression, radiation to bones and surgery to bones. Bone fractures and SSE are both correlated with worse overall survival(OS). Concomitant use of novel anti-androgens further increases the risk of falls and fractures. The earlier and appropiriate intervention with vitamin D and bone modifying agents(BMA)is necessary to prevent treatment related bone fractures and SSE. Bone management algorithm aids to decide the timing and doses of BMA. As for sarcopenia physical exercise and life style advices are important. Because abiraterone with glucocorticoid therapy induces stronger bone resorption, it is recommended to start denosumab simultaneously. Ra-223, bone seeking radiopharmaceuticals should not be used with abiraterone and predonisone because of high incidence of fracture and death.

Evaluation of production cross-sections for 186Re theranostic radionuclide via charged-particle induced reactions on Tungsten

186Re (T1/2 = 89.24 h, E(β−)mean= 346.7 keV, I(β−)total=92.59%), an intense beta-emitter shows great potential to be used as an active material in therapeutic radiopharmaceuticals due to its suitable physico-chemical properties. 186Re can be produced in several ways, however charged-particle induced reactions show to be promising towards no carrier added production. In this work, production cross-sections of 186Re were evaluated following the light-charged particle induced reactions on tungsten. An effective evaluation technique such as Simultaneous Evaluation on KALMAN code combined with least squares concept was used to obtain the evaluated data together with covariances. Knowledge of the underlying uncertainties in evaluated nuclear data, i.e., covariances are useful to improve the accuracy of nuclear data.

Impact of Nuclear Medicine and Radiopharmaceuticals on Health-care Delivery: Advances, Lessons, and Need for an Objective Value-matrix.

The nuclear medicine (NM) growth has gone through both evolutionary and revolutionary changes over decades, mostly attributable to the dynamic and responsive trends in the global development and deployment of radiopharmaceuticals (RPh), as well as the advent of superior technology imaging systems (single-photon emission computed tomography/computed tomography [CT], positron emission tomography [PET]/CT, PET/magnetic resonance) with quantification capability. There are naturally many crucial lessons learnt along the way of NM-RPh progress achieved. It is felt imperative for the NM-RPh community to have consensus-based list(s) of indications for NM, classified on the value-level basis, at NM gross-level and specific medical specialty-wise, and the corresponding RPh needed, to ensure harmonious communication with the referral medical fraternity and health-care policymakers. For this purpose, a “NM value-matrix” is proposed in terms of “NM utility grading” (unique value, significant value, useful value, and others) versus “patient volume” (i.e., large, medium, low, and rare cases), covering the established and emerging indications for NM procedure, and the corresponding RPh product(s) in use. A consensus-based NM Value-Matrix will portray in an unequivocal manner, the merits of NM-RPh options (also limitations, if any) for serving needy patients.