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EJNMMI Radiopharmacy and Chemistry Jul 2022Radionuclide therapy (RNT) has become a very important treatment modality for cancer nowadays. Comparing with other cancer treatment options, sufficient efficacy could...
BACKGROUND
Radionuclide therapy (RNT) has become a very important treatment modality for cancer nowadays. Comparing with other cancer treatment options, sufficient efficacy could be achieved in RNT with lower toxicity. β emitters are frequently used in RNT due to the long tissue penetration depth of the β particles. The dysprosium-166/holmium-166 (Dy/Ho) in vivo generator shows great potential for treating large malignancies due to the long half-life time of the mother nuclide Dy and the emission of high energy β from the daughter nuclide Ho. However, the internal conversion occurring after β decay from Dy to Ho could cause the release of about 72% of Ho when Dy is bound to conventional chelators. The aim of this study is to develop a nanoparticle based carrier for Dy/Ho in vivo generator such that the loss of the daughter nuclide Ho induced by internal conversion is prevented. To achieve this goal, we radiolabelled platinum-gold bimetallic nanoparticles (PtAuNPs) and core-shell structured gold nanoparticles (AuNPs) with Dy and studied the retention of both Dy and Ho under various conditions.
RESULTS
The Dy was co-reduced with gold and platinum precursor to form the DyAu@AuNPs and DyPtAuNPs. The Dy radiolabelling efficiency was determined to be 60% and 70% for the two types of nanoparticles respectively. The retention of Dy and Ho were tested in MiliQ water or 2.5 mM DTPA for a period of 72 h. In both cases, more than 90% of both Dy and Ho was retained. The results show that the incorporation of Dy in AuNPs can prevent the escape of Ho released due to internal conversion.
CONCLUSION
We developed a chelator-free radiolabelling method for Dy with good radiolabelling efficiency and very high stability and retention of the daughter nuclide Ho. The results from this study indicate that to avoid the loss of the daughter radionuclides by internal conversion, carriers composed of electron-rich materials should be used.
PubMed: 35852733
DOI: 10.1186/s41181-022-00170-3 -
Scientific Reports Mar 2017Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its β emission results in very efficient energy deposition in...
Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its β emission results in very efficient energy deposition in small-size tumours. Because of this, Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, Lu and Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation. Based on this separation concept, a new type of radionuclide generator has been devised, in which the parent and the daughter radionuclides are the same elements. The Lu/Lu radionuclide generator provides a new production route for the therapeutic radionuclide Lu and can bring significant growth in the research and development of Lu based pharmaceuticals.
Topics: Animals; Humans; Lutetium; Neoplasms; Radioactivity; Radioisotopes; Radiopharmaceuticals
PubMed: 28287131
DOI: 10.1038/srep44242 -
Journal of Nuclear Cardiology :... Oct 2020Strontium-82/Rubidium-82 (Sr/Rb) generators are used widely for positron emission tomography (PET) imaging of myocardial perfusion. In this study, the Rb isotope yield... (Comparative Study)
Comparative Study
INTRODUCTION
Strontium-82/Rubidium-82 (Sr/Rb) generators are used widely for positron emission tomography (PET) imaging of myocardial perfusion. In this study, the Rb isotope yield and production efficiency of two FDA-approved Sr/Rb generators were compared.
METHODS
N = 515 sequential daily quality assurance (QA) reports from 9 CardioGen-82 and 9 RUBY-FILL generators were reviewed over a period of 2 years. A series of test elutions was performed at different flow-rates on the RUBY-FILL system to determine an empirical correction-factor used to convert CardioGen-82 daily QA values of Rb activity (dose-calibrator 'maximum' of 50 mL elution at 50 mL·min) to RUBY-FILL equivalent values (integrated 'total' of 35 mL elution at 20 mL·min). The generator yield (Rb) and production efficiency (Rb yield/Sr parent activity) were measured and compared after this conversion to a common scale.
RESULTS
At the start of clinical use, the system reported Rb activity from daily QA was lower for CardioGen-82 vs RUBY-FILL (2.3 ± 0.2 vs 3.0 ± 0.2 GBq, P < 0.001) despite having similar Sr activity. Dose-calibrator 'maximum' (CardioGen-82) values were found to under-estimate the integrated 'total' (RUBY-FILL) activity by ~ 24% at 50 mL·min. When these data were used to convert the CardioGen-82 values to a common measurement scale (integrated total activity) the CardioGen-82 efficiency remained slightly lower than the RUBY-FILL system on average (88 ± 4% vs 95 ± 4%, P < 0.001). The efficiency of Rb production improved for both systems over the respective periods of clinical use.
CONCLUSIONS
Rb generator yield was significantly under-estimated using the CardioGen-82 vs RUBY-FILL daily QA procedure. When generator yield was expressed as the integrated total activity for both systems, the estimated Rb production efficiency of the CardioGen-82 system was ~ 7% lower than RUBY-FILL over the full period of clinical use.
Topics: Heart Diseases; Humans; Myocardial Perfusion Imaging; Positron-Emission Tomography; Quality Assurance, Health Care; Radionuclide Generators; Retrospective Studies; Rubidium Radioisotopes; Strontium Radioisotopes
PubMed: 32436115
DOI: 10.1007/s12350-020-02200-6 -
Journal of Nuclear Medicine : Official... Jan 2023The feasibility, performance, and radiation safety of an experimental generator were evaluated to efficiently produce Pb intended for radiopharmaceuticals. The...
The feasibility, performance, and radiation safety of an experimental generator were evaluated to efficiently produce Pb intended for radiopharmaceuticals. The generator consisted of a flask with a removable cap containing a source of Ra or Th absorbed on quartz wool. Gaseous Rn emanated from the decaying source, which subsequently decayed to Pb, which was adsorbed on the flask's interior surface. The Pb was collected by washing the flask with 0.5-1 mL of 0.1 M HCl. The generator collector flask trapped 62%-68% of the Pb, of which more than 87% (tested up to 26 MBq) could be harvested. The obtained Pb solution had a high purity (>99.98%) and could be used for the preparation of radioconjugates with more than 97% radiochemical purity. Future designs of the generator should aim to further reduce the risk of radon and γ-energy exposure to operators. The presented technology is a promising method for easy and convenient Pb production.
Topics: Radiopharmaceuticals; Lead; Isotope Labeling; Radiochemistry; Lead Radioisotopes
PubMed: 35798556
DOI: 10.2967/jnumed.122.264009 -
EJNMMI Radiopharmacy and Chemistry Jul 2019In this work, a lutetium-177 (Lu) production method based on the separation of nuclear isomers, Lu & Lu, is reported. The Lu-Lu separation is performed by combining the...
BACKGROUND
In this work, a lutetium-177 (Lu) production method based on the separation of nuclear isomers, Lu & Lu, is reported. The Lu-Lu separation is performed by combining the use of DOTA & DOTA-labelled peptide (DOTATATE) and liquid-liquid extraction.
METHODS
The Lu cations were complexed with DOTA & DOTATATE and kept at 77 K for periods of time to allow Lu production. The freed Lu ions produced via internal conversion of Lu were then extracted in dihexyl ether using 0.01 M di-(2-ethylhexyl) phosphoric acid (DEHPA) at room temperature. The liquid-liquid extractions were performed periodically for a period up to 35 days.
RESULTS
A maximum Lu/Lu activity ratio of 3500 ± 500 was achieved with [Lu]Lu-DOTA complex, in comparison to Lu/Lu activity ratios of 1086 ± 40 realized using [Lu]Lu-DOTATATE complex. The Lu-Lu separation was found to be affected by the molar ratio of lutetium and DOTA. A Lu/Lu activity ratio up to 3500 ± 500 was achieved with excess DOTA in comparison to Lu/Lu activity ratio 1500 ± 600 obtained when lutetium and DOTA were present in molar ratio of 1:1. Further, the Lu ion extraction efficiency, decreases from 95 ± 4% to 58 ± 2% in the presence of excess DOTA.
CONCLUSION
The reported method resulted in a Lu/ Lu activity ratio up to 3500 after the separation. This ratio is close to the lower end of Lu/Lu activity ratios, attained currently during the direct route Lu production for clinical applications (i.e. 4000-10,000). This study forms the basis for further extending the liquid-liquid extraction based Lu-Lu separation in order to lead to a commercial Lu/Lu radionuclide generator.
PubMed: 31659496
DOI: 10.1186/s41181-019-0064-5 -
Journal of Nuclear Medicine : Official... Sep 2020The coronavirus disease 2019 (COVID-19) pandemic has placed significant challenges on health-care systems worldwide, whether in the preparation, response, or recovery...
The coronavirus disease 2019 (COVID-19) pandemic has placed significant challenges on health-care systems worldwide, whether in the preparation, response, or recovery phase of the pandemic. This has been primarily managed by dramatically reducing in- and outpatient services for other diseases and implementing infection prevention and control measures. The impact of the pandemic on nuclear medicine departments and their services has not yet been established. The aim of this online survey was to evaluate the impact of COVID-19 on nuclear medicine departments. A web-based questionnaire, made available from April 16 to May 3, 2020, was designed to determine the impact of the pandemic on in- and outpatient nuclear medicine departments, including the number of procedures, employee health, availability of radiotracers and other essential supplies, and availability of personal protective equipment. The survey also inquired about operational aspects and types of facilities as well as other challenges. A total of 434 responses from 72 countries were registered and analyzed. Respondents reported an average decline of 54% in diagnostic procedures. PET/CT scans decreased by an average of 36%, whereas sentinel lymph-node procedures decreased by 45%, lung scans by 56%, bone scans by 60%, myocardial studies by 66%, and thyroid studies by 67%. Of all participating centers, 81% performed radionuclide therapies, and they reported a reduction of 45% on average in the last 4 wk, ranging from over 76% in Latin America and South East Asia to 16% in South Korea and Singapore. Survey results showed that 52% of participating sites limited their Tc/Mo generator purchases, and 12% of them temporarily cancelled orders. Insufficient supplies of essential materials (radioisotopes, generators, and kits) were reported, especially for Tc/Mo generators and I, particularly in Africa, Asia, and Latin America. Both diagnostic and therapeutic nuclear medicine procedures declined precipitously, with countries worldwide being affected by the pandemic to a similar degree. Countries that were in the postpeak phase of the pandemic when they responded to the survey, such as South Korea and Singapore, reported a less pronounced impact on nuclear medicine services; however, the overall results of the survey showed that nuclear medicine services worldwide had been significantly impacted. In relation to staff health, 15% of respondents experienced COVID-19 infections within their own departments.
Topics: COVID-19; Coronavirus Infections; Hospital Departments; Humans; Internationality; Pandemics; Pneumonia, Viral; Surveys and Questionnaires
PubMed: 32709733
DOI: 10.2967/jnumed.120.249821 -
Molecules (Basel, Switzerland) Oct 2021Today, Sc is an attractive radionuclide for molecular imaging with PET. In this work, we evaluated a Ti/Sc radionuclide generator based on TEVA resin as a source of Sc....
Today, Sc is an attractive radionuclide for molecular imaging with PET. In this work, we evaluated a Ti/Sc radionuclide generator based on TEVA resin as a source of Sc. The generator prototype (5 MBq) exhibits high Ti retention and stable yield of Sc (91 ± 6 %) in 1 mL of eluate (20 bed volumes, eluent-0.1 M oxalic acid/0.2 M HCl) during one year of monitoring (more than 120 elutions). The breakthrough of Ti did not exceed 1.5 × 10% (average value was 6.5 × 10%). Post-processing of the eluate for further use in radiopharmaceutical synthesis was proposed. The post-processing procedure using a combination of Presep PolyChelate and TK221 resins made it possible to obtain Sc-radioconjugates with high labeling yield (≥95%) while using small precursor amounts (5 nmol). The proposed method takes no more than 15 min and provides ≥90% yield relative to the Sc activity eluted from the generator. The labeling efficiency was demonstrated on the example of [Sc]Sc-PSMA-617 and [Sc]Sc-PSMA-I&T synthesis. Some superiority of PSMA-I&T over PSMA-617 in terms of Sc labeling efficiency was demonstrated (likely due to presence of DOTAGA chelator in the precursor structure). It was also shown that microwave heating of the reaction mixture considerably shortened the reaction time and improved radiolabeling yield and reproducibility of [Sc]Sc-PSMA-617 and [Sc]Sc-PSMA-I&T synthesis.
Topics: Chelating Agents; Chemical Fractionation; Chemistry Techniques, Synthetic; Chromatography; Dipeptides; Heterocyclic Compounds, 1-Ring; Isotope Labeling; Kinetics; Prostate-Specific Antigen; Radioisotopes; Radiopharmaceuticals; Resins, Synthetic; Scandium; Titanium
PubMed: 34770780
DOI: 10.3390/molecules26216371 -
ChemMedChem Mar 2021The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through...
The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood-brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [ Ga]Ga-HBED-hexadiyne-tropane, showed an IC value of 66 nM, together with a log D of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.
Topics: Animals; Blood-Brain Barrier; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; Gallium Radioisotopes; Male; Molecular Structure; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Wistar; Structure-Activity Relationship; Tropanes
PubMed: 33245194
DOI: 10.1002/cmdc.202000820 -
Brain and Behavior Mar 2019The applicability of "Rubidium Chloride, Rb from Generator" radiopharmaceutical for brain tumors (BT) diagnostics is demonstrated on the basis of the application...
INTRODUCTION
The applicability of "Rubidium Chloride, Rb from Generator" radiopharmaceutical for brain tumors (BT) diagnostics is demonstrated on the basis of the application experience of the radiopharmaceutical in neurooncology.
EXPERIMENTAL
A total of 21 patients with various brain tumors and nonneoplastic abnormal brain masses were investigated.
RESULTS AND DISCUSSIONS
The results of the imaging and differential diagnostics of malignant and benign tumors, nonneoplastic abnormal brain masses and lesions revealed the prevalence of high uptake of the radiopharmaceutical in the malignant tumors in comparison with benign glioma and arteriovenous malformations in which Rb-chloride accumulates in the vascular phase but does not linger further. The ultra-short half-life of radionuclide Rb (76 s) along with a low absorbed radiation dose with Rb-chloride by intravenous administration create a new possibility of successive use of two or more radiopharmaceuticals for the examination of the same patient. For instance, PET examination with F-FDG, C-methionine, C-choline, or any other radiopharmaceutical can be carried out in just 7-15 min. after Rb-chloride injection.
CONCLUSION
Research demonstrated an effectiveness of Rb-chloride application as a diagnostic agent in neurooncology. A method of dosing and administration of the generator-produced radiopharmaceutical has been worked out. It is possible to do up to 600 PET sessions using one Russian Rb generator GR-01. The generator is proved to be reliable and easy to use. The interest in Rb-chloride as a tumor-seeking radiopharmaceutical rose due to the active application of the modern devices PET/CT in the routine clinical practice.
Topics: Brain; Brain Neoplasms; Chlorides; Diagnosis, Differential; Humans; Medical Oncology; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Rubidium; Strontium Radioisotopes
PubMed: 30729720
DOI: 10.1002/brb3.1212 -
Pharmaceuticals (Basel, Switzerland) Aug 2023[Ga]Ga-FAPI-46 is a radiolabelled fibroblast activation protein inhibitor that selectively binds to fibroblast activation protein (FAP), which is overexpressed by...
[Ga]Ga-FAPI-46 is a radiolabelled fibroblast activation protein inhibitor that selectively binds to fibroblast activation protein (FAP), which is overexpressed by cancer-associated fibroblasts (CAFs) in the tumour microenvironment. In recent years, radiolabelled FAP inhibitors (FAPIs) are becoming increasingly important in cancer diagnostics and also for targeted radionuclide therapy. Because of the increasing demand for radiolabelled FAPIs, automating the synthesis of these compounds is of great interest. In this work, we present a newly programmed automatic synthesis process of [Ga]Ga-FAPI-46 on a Scintomics GRP module using two Galli Ad generators as a radionuclide source. Dedicated cassettes for the labelling of Ga-peptides were used without any modifications. The generators were connected via a three-way valve to the module and eluted automatically over a strong cation exchange (SCX) cartridge by using the vacuum pump of the synthesis module, eliminating the need to transfer the eluates into a separate vial. After a reaction step in HEPES buffer, the compound was purified by solid-phase extraction (SPE) over a Sep-Pak Light C18 cartridge. The evaluation of 10 routine syntheses of [Ga]Ga-FAPI-46 resulted in a radiochemical yield of 72.6 ± 4.9%. The radiochemical purity was 97.6 ± 0.3%, and the amount of free gallium-68 and colloid was <2%. The final product fulfilled the quality criteria, which were adapted from relevant monographs of the (Ph. Eur.). This work presents the successful preparation of multiple doses of [Ga]Ga-FAPI-46 in a GMP-compliant automated process for clinical use.
PubMed: 37631053
DOI: 10.3390/ph16081138