Preparation Of Radiopharmaceuticals Research Articles

Challenges in the solution phase synthesis of PSMA-11 and PSMA-617: organic ligands for radiopharmaceutical preparations in prostate cancer medication

Abstract Patient specific treatments for different cancers are currently being actively addressed through nuclear medicine. More recently, the identification of biomarker namely; prostate-specific membrane antigen (PSMA) expressed on the prostate cancer cell surface has been considered as a turning point in prostate cancer management using radiopharmaceuticals. In this treatment method, apart from radionuclide, organic ligands that target PSMA constitute an essential component. PSMA-11 and PSMA-617 are two important ligands that form the radiopharmaceuticals, [68Ga]Ga-PSMA-11, [177Lu]Lu-PSMA-617, which are currently powering the prostate cancer management, especially metastatic castration resistant prostate cancer (mCRPC) in most part of the world. Identification of efficient synthetic routes towards these highly expensive ligands is an important prerequisite to make this treatment modality more popular. In this account, the synthetic challenges that we circumvent during the solution phase synthesis of PSMA-11 and PSMA-617, through different chemical synthetic routes are demonstrated. Post-synthesis, both the ligands, PSMA-11 and PSMA-617 were successfully radiolabelled using 68Ga, and 177Lu, respectively, to generate corresponding labelled products [68Ga]Ga-PSMA-11, and [177Lu]Lu-PSMA-617, in good radiochemical purity.

Synthesis of a [18F]F Estradiol Derivative via Click Chemistry Using an Automated Synthesis Module: In Vitro Evaluation as Potential Radiopharmaceutical for Breast Cancer Imaging.

"Click reactions" are a very useful tool for the selective conjugation of different molecular subunits to produce complex structures in a simple way. In this paper, we present the application of Cu(I)-catalyzed biorthogonal reactions between alkynes and azides to the indirect radiofluorination of an estradiol derivative with potential applications in estrogen receptor imaging. The procedure was fully developed on an automated synthesis platform, and conditions were optimized to achieve the desired product with a reasonable yield without precipitation. Although the biological results were not adequate for a potential radiopharmaceutical, the outcome of this work is valuable since the use of automated platforms is required for the reliable and reproducible preparation of PET radiopharmaceuticals in GMP conditions while limiting the radiation dose rates to the personnel.

Evaluation of acute intravenous toxicity of HEPES: Is Good's buffer good and safe enough for clinical utilization in nuclear medicine?

ObjectiveGood's buffer or HEPES has advantages over other buffers commonly used in radiopharmaceutical preparation as it exhibits significantly lower complexation tendency with metal ions. However, use of HEPES buffer for radiolabeling reactions, meant for clinical applications, has been underrated due to the non-availability of sufficient toxicity data. The objective of the present study is to find the evidences towards safety of intravenous administration of HEPES through systemic toxicological studies in small animal model to support its safe application for clinical exploitation. ExperimentalA pilot study was performed to investigate the lethal dose of HEPES in female Sprague Dawley rats by administering seven different doses of HEPES solution (150 to 2000 mg/kg), through intravenous pathway. Similarly, for determining maximum tolerated dose (MTD), gradually increasing doses of HEPES (50 to 950 mg/kg) were administered in the same species via similar pathway. Various hematological and clinical pathological investigations were carried out in order to find out the safe administration dose of HEPES in rats. ResultsNo mortality was observed up to 2000 mg/kg doses of HEPES. The doses beyond 300 mg/kg resulted few temporary adverse effects, though these were found to disappear within 4–5 days of dosing. ConclusionThe amount of HEPES to be administered during clinical intervention is usually much lower (typically 1–2.5 mg per kg of body weight of healthy adult) than the MTD determined in rat model during present report. Hence, the utilization of this buffer for preparation of radiolabeled drugs for human investigation may be safe. However, further detailed investigations may be warranted for supporting the candidature of Good's buffer for regular clinical exploitation.

Biodistribution study of 211Pb progeny released from intravenously applied 223Ra labelled TiO2 nanoparticles in a mouse model

BackgroundTargeted alpha therapy is one of the most powerful therapeutical modalities available in nuclear medicine. It's therapeutic potency is based on the nuclides that emit one or several alpha particles providing strong and highly localized therapeutic effects. However, some of these radionuclides, like e.g.223Ra or 225Ac decay in cascades, where the radioactive progeny originating from the consecutive alpha-decays may leave the original vector and cause unwanted irradiation of non-target organs. This progeny, even if partially retained in target tissues by internalization processes, typically do not follow the fate of originally targeted radiopharmaceutical and potentially spread over body following their own biodistribution. In this study we aimed to estimate 211Pb/211Bi progeny fate from the 223Ra surface-labelled TiO2 nanoparticles in vitro and the fate of 211Pb in vivo in a mice model. ResultsIn vitro stability studies have shown significant differences between the release of the mother 223Ra and its progeny (211Pb, 211Bi) in all the biological matrices that have been tested. The lowest released activities were measured in saline, resulting in less than 5 % of released activity for all nuclides. Contrary to that, the highest released activity of 223Ra of up to 10 % within 48 h was observed in 5 % solution of albumin. The released activity of its progeny; the 211Pb and 211Bi was in the range of 20–40 % in this test medium. Significantly higher released activities of 211Pb and 211Bi compared to 223Ra by at least 10 % was observed in each biological medium, except saline, where no significant differences were observed. The in vivo biodistribution studies results in a mice model, show similar pattern, where it was found that even after accumulation of nanoparticles in target tissues, approximately 10 % of 211Pb is continuously released into the blood stream within 24 h, followed by its natural accumulation in kidneys. ConclusionThis study confirms our assumption that the progeny formed in a chain alpha decay of a certain nuclide, in this case the 223Ra, can be released from its original vector, leave the target tissue, relocate and could be deposited in non-target organs. We did not observe complete progeny wash-out from its original target tissues in our model. This indicates strong dependence of the progeny hot atom fate after its release from the original radiopharmaceutical preparation on multiple factors, like their internalization and retention in cells, cell membranes, extracellular matrices, protein binding, etc. We hypothesize, that also the primary tumour or metastasis size, their metabolic activity may significantly influence progeny fate in vivo, directly impacting the dose delivered to non-target tissues and organs. Therefore a bottom-up approach should be followed and detailed pre-/clinical studies on the release and biodistribution of radioactive progeny originating from the chain alpha emitters should be preferably performed.

Risk Management in Good Manufacturing Practice (GMP) Radiopharmaceutical Preparations

Risk assessment and management during the entire production process of a radiopharmaceutical are pivotal factors in ensuring drug safety and quality. A methodology of quality risk assessment has been performed by integrating the advice reported in Eudralex, ICHQ, and ISO 9001, and its validity has been evaluated by applying it to real data collected in 21 months of activities of 18F-FDG production at Officina Farmaceutica, CNR-Pisa (Italy) to confirm whether the critical aspects that previously have been identified in the quality risk assessment were effective. The analysis of the results of the real data matched the hypotheses obtained from the model, and in particular, the most critical aspects were those related to human resources and staff organization with regard to management risk. Regarding the production process, the model of operational risk had predicted, as later confirmed by real data, that the most critical phase could be the synthesis and dispensing of the radiopharmaceuticals. So, the proposed method could be used by other similar radiopharmaceutical production sites to identify the critical phases of the production process and to act to improve performance and prevent failure in the entire cycle of radiopharmaceutical products.

Effective radiopharmaceutical preparations for the labelling of technetium-99m in gastric emptying scans, a review

Effective radiopharmaceutical preparations for the labelling of technetium-99m in gastric emptying scans, a review

Preclinical Evaluation and a Pilot Clinical Positron Emission Tomography Imaging Study of [68Ga]Ga-FAPI-FUSCC-II.

Fibroblast activation protein (FAP), a type II integral membrane serine protease, is a promising target for tumor diagnosis and therapy. OncoFAP has been recently discovered for PET imaging procedures for various solid malignancies. In this study, we presented the development of manual radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging. A novel series of [68Ga/177Lu]Ga/Lu-FAPI-FUSCC-I/II were produced with high radiochemical yields. [68Ga]Ga-FAPI-FUSCC-I/II and [177Lu]Lu-FAPI-FUSCC-I/II were stable in phosphate-buffered saline, fetal bovine serum, and human serum for at least 3 h. In vitro cellular uptake and blocking experiments implied that they had specificity to FAP. Additionally, the low nanomolar IC50 values of FAPI-FUSCC-II indicated that it had a high target affinity to FAP. The in vivo biodistribution and blocking study in mice bearing HT-1080-FAP tumors showed that both exhibited specific tumor uptake. [68Ga]Ga-FAPI-FUSCC-II showed a higher tumor uptake and a higher tumor/nontarget ratio than [68Ga]Ga-FAPI-FUSCC-I and [68Ga]Ga-FAPI-04. The results of ex vivo biodistribution were in accordance with the biodistribution results. Clinical [68Ga]Ga-FAPI-FUSCC-II-PET/CT imaging further demonstrated its favorable biodistribution and kinetics with elevated and reliable uptake by primary tumors (maximum standardized uptake value (SUVmax), 12.17 ± 6.67) and distant metastases (SUVmax, 9.24 ± 4.28). In summary, [68Ga]Ga-FAPI-FUSCC-II displayed increased tumor uptake and retention compared to [68Ga]Ga-FAPI-04, giving it potential as a promising tracer for the diagnostic imaging of malignant tumors with positive FAP expression.

Position paper to facilitate patient access to radiopharmaceuticals: considerations for a suitable pharmaceutical regulatory framework.

Nuclear medicine has made enormous progress in the past decades. However, there are still significant inequalities in patient access among different countries, which could be mitigated by improving access to and availability of radiopharmaceuticals. This paper summarises major considerations for a suitable pharmaceutical regulatory framework to facilitate patient access to radiopharmaceuticals. These include the distinct characteristics of radiopharmaceuticals which require dedicated regulations,considering the impact of the variable complexity of radiopharmaceutical preparation, personnel requirements, manufacturing practices and quality assurance, regulatory authority interfaces, communication and training, as well as marketing authorisation procedures to ensure availability of radiopharmaceuticals. Finally, domestic and regional supply to ensure patient access via alternative regulatory pathways, including in-house production of radiopharmaceuticals, is described, and an outlook on regulatory challenges faced by new developments, such as the use of alpha emitters, is provided. All these considerations are an outcome of a dedicated Technical Meeting organised by the IAEA in 2023 and represent the views and opinions of experts in the field, not those of any regulatory authorities.

P-209 - A novel radioiodination method for the preparation of radiopharmaceuticals

P-209 - A novel radioiodination method for the preparation of radiopharmaceuticals

Measurement of Radiation Exposure of Hands and Fingers of Nuclear Medicine Personnel Using Innovative Low-Cost GM Based System

Pocket dosimeters are used commonly in Nuclear Medicine or radiology workers for daily dose measurement or during certain high radiation exposure procedures for short periods of time. These are expensive and have many maintenance costs. It may not be feasible to procure many at a time due to cost restraints. We designed a low cost remote dose monitoring device for measurement of radiation for short periods of time. Measuring device was constructed using micro Geiger Muller Counter. The micro-Geiger Counter with model no SBM21 was connected to high voltage circuit and the output signal was obtained. After this, output signal was sent it to Arduino circuit running custom code ESP8266 and readings was made on the mobile/ laptop application after connecting to Arduino circuit running custom code ESP8266 via internet. Readings were taken for short durations during certain periods. Readings were compared to the standard measuring instrument simultaneously. The tube was connected to their hands for hand exposure with a wire. Readings were recorded in the form of μSv/h or mSv/h. RESULT: Total readings were taken during various occasions while preparing (59) and dispensing (45) radioisotopes. During preparation of radiopharmaceuticals, average readings for 99mTc-Sestamibi[16 SAMPLE] (100mCi to 250mCi), 99mTc-MDP [21SAMPLE] (150-200mCi) and 99mTc-DTPA [22SAMPLES] (10-20mCi) were 1115 μSv/h, 3083 μSv/h and 453 μSv/h respectively. During dispensing of radiopharmaceuticals, average readings of total 15 sample each for 99mTc-Sestamibi (100mCi to 250mCi), 99mTc-MDP (150-200mCi) and 99mTc-DTPA (10-20mCi) were 351μSv/h, 209 μSv/h and 235 μSv/h respectively. It was feasible for the worker to fit the measuring device in their pocket while working. Conclusion: Our pilot study revealed accurate readings >95% of the times for short periods of time. Study designing, standardization of readings with more real time accuracy can make this method more reliable and is a low cost means to monitor short periods of radiation exposure for radiation workers.

Bacterial survival in radiopharmaceutical solutions: a critical impact on current practices

BackgroundThe aim of this brief communication is to highlight the potential bacteriological risk linked to the processes control of radiopharmaceutical preparations made in a radiopharmacy laboratory. Survival rate of Pseudomonas aeruginosa (ATCC: 27853) or Staphylococcus aureus (ATCC: 25923) or Staphylococcus epidermidis (ATCC: 1228) in multidose technetium-99 m solution was studied.ResultsDepending on the nature and level of contamination by pathogenic bacteria, the lethal effect of radioactivity is not systematically observed. We found that P. aeruginosa was indeed affected by radioactivity. However, this was not the case for S. epidermidis, as the quantity of bacteria found in both solutions (radioactive and non-radioactive) was rapidly reduced, probably due to a lack of nutrients. Finally, the example of S. aureus is an intermediate case where we observed that high radioactivity affected the bacteria, as did the absence of nutrients in the reaction medium. The results were discussed in the light of current practices on the sterility test method, which recommends waiting for radioactivity to decay before carrying out the sterility test.ConclusionIn terms of patient safety, the results run counter to current practice and the latest EANM recommendation of 2021 that radiopharmaceutical preparations should be decayed before sterility testing.

Alpha-induced production and robust radiochemical separation of 43Sc as an emerging radiometal for formulation of PET radiopharmaceuticals

Scandium-43 is an emerging PET radiometal that was produced by α-particle bombardment on natural CaCO3 target via natCa (α,p) 43Sc and natCa (α,n) 43Ti→43Sc reactions using K-130 cyclotron at VECC. A robust radiochemical procedure based on selective precipitation of 43Sc as Sc(OH)3 was developed for separation of the radioisotope from the irradiated target. The overall yield of the separation process was >85% and it was obtained in a form suitable for preparation of target specific radiopharmaceuticals for PET imaging of cancer.

Evaluation of Candidate Theranostics for 227Th/89Zr Paired Radioimmunotherapy of Lymphoma.

227Th is a promising radioisotope for targeted α-particle therapy. It produces 5 α-particles through its decay, with the clinically approved 223Ra as its first daughter. There is an ample supply of 227Th, allowing for clinical use; however, the chemical challenges of chelating this large tetravalent f-block cation are considerable. Using the CD20-targeting antibody ofatumumab, we evaluated chelation of 227Th4+ for α-particle-emitting and radiotheranostic applications. Methods: We compared 4 bifunctional chelators for thorium radiopharmaceutical preparation: S-2-(4-Isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), 2-(4-isothicyanatobenzyl)-1,2,7,10,13-hexaazacyclooctadecane-1,4,7,10,13,16-hexaacetic acid (p-SCN-Bn-HEHA), p-isothiacyanatophenyl-1-hydroxy-2-oxopiperidine-desferrioxamine (DFOcyclo*-p-Phe-NCS), and macrocyclic 1,2-HOPO N-hydroxysuccinimide (L804-NHS). Immunoconstructs were evaluated for yield, purity, and stability invitro and invivo. Tumor targeting of the lead 227Th-labeled compound invivo was performed in CD20-expressing models and compared with a companion 89Zr-labeled PET agent. Results: 227Th-labeled ofatumumab-chelator constructs were synthesized to a radiochemical purity of more than 95%, excepting HEHA. 227Th-HEHA-ofatumumab showed moderate invitro stability. 227Th-DFOcyclo*-ofatumumab presented excellent 227Th labeling efficiency; however, high liver and spleen uptake was revealed invivo, indicative of aggregation. 227Th-DOTA-ofatumumab labeled poorly, yielding no more than 5%, with low specific activity (0.08 GBq/g) and modest long-term invitro stability (<80%). 227Th-L804-ofatumumab coordinated 227Th rapidly and efficiently at high yields, purity, and specific activity (8 GBq/g) and demonstrated extended stability. In vivo tumor targeting confirmed the utility of this chelator, and the diagnostic analog, 89Zr-L804-ofatumumab, showed organ distribution matching that of 227Th to delineate SU-DHL-6 tumors. Conclusion: Commercially available and novel chelators for 227Th showed a range of performances. The L804 chelator can be used with potent radiotheranostic capabilities for 89Zr/227Th quantitative imaging and α-particle therapy.

Multifunctional 99mTc-5-azacitidine Gold Nanoparticles: Formulation, In Vitro Cytotoxicity, Radiosynthesis, and In Vivo Pharmacokinetic Study.

5-azacitidine is a very potent chemotherapeutic agent that suffers from certain disadvantages. This study aims to prepare gold nanoparticles as a new nano-formula of 5-azacitidine that can improve its bioavailability and decrease its side effects. 5-azacytidine-loaded GA-AuNPs were prepared and characterized by UV-Vis spectroscopy, infrared (IR), and electronic transmission microscope (TEM). This new platform was characterized in vitro by measuring its zeta potential, particle size, and drug loading efficacy, and the anti-proliferative effect on the MCF-7 cell line was evaluated. In vivo biodistribution studies of 99mTc-5-aza solution and 99mTc-5-aza-gold nano formula were conducted in tumor-bearing mice by different routes of administration (intravenous and intra-tumor). 5-Aza-GA-AuNPs formula was successfully prepared with an optimum particle size of ≈34.66 nm, the zeta potential of -14.4 mV, and high entrapment efficiency. 99mTc-5-Aza-GA-AuNPs were successfully radiosynthesized with a labeling yield of 95.4%. Biodistribution studies showed high selective accumulation in tumor and low uptake in non-target organs in the case of the 5-Aza-GA-AuNPs formula than the 99mTc-5-azacitidine solution. 99mTc-5-Aza-GA-AuNPs improved the selectivity and uptake of 5-azacitidine in cancer. Moreover, 99mTc-5-Aza-GA-AuNPs could be used as hopeful theranostic radiopharmaceutical preparation for cancer.

18F]Tosyl fluoride as a versatile [18F]fluoride source for the preparation of 18F-labeled radiopharmaceuticals

Positron emission tomography (PET) is an in vivo imaging technology that utilizes positron-emitting radioisotope-labeled compounds as PET radiotracers that are commonly used in clinic and in various research areas, including oncology, cardiology, and neurology. Fluorine-18 is the most widely used PET-radionuclide and commonly produced by proton bombardment of 18O-enriched water in a cyclotron. The [18F]fluoride thus obtained generally requires processing by azeotropic drying in order to completely remove H2O before it can be used for nucleophilic radiofluorination. In general, the drying step is important in facilitating the radiofluorination reactions and the preparation of 18F-labeled PET radiotracers. In this communication, we have demonstrated the feasibility of using [18F]tosyl fluoride ([18F]TsF) as a versatile [18F]fluoride source for radiofluorination to bypass the azeotropic drying step, and we have developed a continuous flow solid-phase radiosynthesis strategy to generate [18F]TsF in a form that is excellent for radiofluorination. [18F]TsF shows high reactivity in radiofluorination and provides the features suitable for preparing PET radiotracers on a small scale and exploring novel radiolabeling technologies. Thus, using [18F]TsF as a [18F]fluoride source is a promising strategy that facilitates radiofluorination and provides a convenient and efficient solution for the preparation of 18F-labeled radiopharmaceuticals that is well matched to the emerging trends in PET imaging technologies.

Occupational exposure level and requirements for radiation protection of nuclear medical staff

With the rapid development of nuclear medicine, the number of nuclear medical staff has increased a lot in the past few years in China. Close-range operations, such as preparation and injections of radiopharmaceuticals, are usually carried out in nuclear medicine department. And the use of unsealed radionuclides may also create internal exposure risk. So, occupational exposure of nuclear medical staff is a main issue of occupational health management in China. In this paper, the occupational exposure level and requirements for radiation protection of nuclear medical staff are introduced to provide references for the related work that radiological health technical institutions carry out.

Finger doses due to 68Ga-labelled pharmaceuticals in PET departments—results of a multi-centre pilot study

Introduction: Although the use of 68Ga has increased substantially in nuclear medicine over the last decade, there is limited information available on occupational exposure due to 68Ga. The purpose of this study is to determine the occupational extremity exposure during the preparation, dispensing and administration of 68Ga-labelled radiopharmaceuticals. Method: Workers in eight centres wore a ring dosimeter for all tasks involving 68Ga-labelled radiopharmaceuticals for a minimum of one month. Additionally, the fingertip dose was monitored in two centres and the hand with the highest ring dose during 68Ga procedures was also identified in one centre. Results: The median normalised ring dose for 68Ga procedures was found to be 0.25 mSv GBq−1 (range 0.01–3.34). The normalised 68Ga ring doses recorded in this study are similar to that found in the literature for 18F. This study is consistent with previous findings that the highest extremity dose is found on the non-dominant hand. A limited sub study in two of the centres showed a median fingertip to base of the finger dose ratio of 4.3. Based on this median ratio, the extrapolated annual 68Ga fingertip dose for 94% of the workers monitored in this study would be below Category B dose limit (150 mSv) and no worker would exceed Category A dose limit (500 mSv). Conclusion: When appropriate shielding and radiation protection practices are employed, the extremity dose due to 68Ga is comparable to that of 18F and is expected to be well below the regulatory limits for the majority of workers.

Electrochemical separation and purification of no-carrier-added 177Lu for radiopharmaceutical preparation: Translation from bench to bed

The entry of no-carrier-added (NCA) 177Lu in the arena of clinical nuclear medicine has revolutionized the practice of targeted radionuclide tumor therapy. In this study, we report the development of an electrochemical separation and purification procedure to obtain NCA 177Lu in a clinically usable form. The overall yield of the process developed was > 70% and it was reproducible in multiple batches. The effective specific activity of NCA 177Lu was 3.32 ± 0.04 TBq/mg and the radioisotope was found suitable for formulation of therapeutically relevant doses of [177Lu]Lu-DOTA-TATE with >98% radiolabeling yield. As a proof of concept, [177Lu]Lu-DOTA-TATE synthesized using electrochemically purified NCA 177Lu was administered in patients with proven neuroendocrine tumor (NET) and satisfactory preliminary clinical outcome was obtained. The feasibility of recovery of enriched (in 176Yb) target in chemical form suitable for reuse in the production of a fresh batch of NCA 177Lu was demonstrated, which makes the process economically viable. Overall, this robust and efficient radiochemical separation and purification technology might aid towards introduction of new 177Lu-based radiopharmaceuticals for use in clinical context in the foreseeable future.

Partie 3. Aspects structurels spécifiques du service de médecine nucléaire

A nuclear medicine department is made up of several sectors whose layout, governed by the level of exposure to radiation (“cold” or “hot” sectors), must necessarily take into account the constraints of preparation and distribution of radiopharmaceuticals, storage/management of contaminated waste and effluent, and the patient pathway (reception, MRP injection, image acquisition. ASN Guide No. 32 specifically specifies the rules for the design and operation of nuclear medicine departments. Without forgetting that the ASN is not the only body with requirements concerning the structuring of a service, it is sometimes complex to modulate the premises in an optimal way with all the difficulties and architectural specificities that this can cause. anticipated RIV, through its impact on the layout of the service, is a structural issue in the short/medium term.

Determination of volume-specific correction factors and geometry effects of 90Y activity measurement in dose calibrators

Background: Yttrium-90 (90Y) is widely used in nuclear medicine for therapeutic purposes. The radiation dose of radiopharmaceuticals relates to the activity of the radionuclide which is measured in the dose calibrator during radiopharmaceutical preparations. Objectives: The objectives of this study were to determine volume-specific correction factors and investigate the geometry effects of 90Y activity measurement in dose calibrators. Materials and methods: Four dose calibrators from two institutes were independently measured. The 3-mL plastic syringe and the 10-mL glass vial were used to investigate the geometry effects using the initial calibration factors for each dose calibrator. The comparison between actual activity and measured activity was expressed as the percentage errors. For volume-specific correction factor, the value for each volume was calculated based on the actual and measured activity at 0.5, 1.0, 1.5, 2.0 and 2.5 mL. Results: Percentage error showed that 90Y activity measured in the 3-mL plastic syringe and the 10-mL glass vial were inaccurate. The activity measurements in the 3-mL plastic syringe were more accurate than in the 10-mL glass vial at all volumes for both containers in all dose calibrators. Our findings showed that increasing the volume of 90Y could result in underestimate of the measured activity. The maximum volume dependence in the 10-mL glass vial was about 20%. Hence, the volume-specific correction factors were determined for the 3-mL plastic syringe and the 10-mL glass vial for all dose calibrators. Conclusion: The geometry effect could impact the 90Y activity measurement on the dose calibrators. Using the volume-specific correction factor for each geometry of 90Y to compensate for the geometry effect could improve the accuracy of 90Y activity measurement. However, the volume-specific correction factors are depended on the dose calibrators. Therefore, the institutes need to establish their own volumespecific correction factors for 90Y activity measurement.