A proof of principle study using radiopharmaceuticals to quantify and localize container-content interactions in medical syringes.

The sorption of drugs onto their contents is a known phenomenon that is difficult to analyse precisely. The purpose of this study was to present a non-invasive method for locating and quantifying sorption phenomena using radiopharmaceuticals. Radiopharmaceutical are medicines armed with a radionuclide enabling quantification and imaging using dedicated scanners. The sorption of nine different radiopharmaceuticals on 2- and 3-part syringes was investigated. These syringes were filled with the studied radiopharmaceutical solutions and stored immobile for 3 h. At different times ranging from 0 to 180 min, 10 µL were taken from the syringes and the radioactivity of these samples was determined by a gamma counter. 5 radiopharmaceuticals exhibited no significant sorption at any time point in both 2 and 3-parts syringes, but 4 radiopharmaceuticals exhibited sorption losses varying from 20 to 33% after 3 h contact with 3-part-syringes, but no sorption on 2-part syringes at any time point. [99mTc]Tc-tetrofosmine Single Photon Emission Computed Tomography/Computed Tomography imaging indicated clearly that the interactions were located on the rubber plunger of the 3-part-syringes. The specific nature of radiopharmaceuticals allowed their use as an innovative method to quantify and localize drug sorption phenomena.

Transferability of a two-strip method for the quality control of technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3).

OBJECTIVES: Technetium-99m mercapto-acetyl-triglycine ([99mTc]Tc-MAG3) is a radiopharmaceutical diagnostic agent used in nuclear medicine intended for the exploration of nephrological and urological disorders. Patient safety and reliability of this imaging procedure especially depend on the radiochemical purity (RCP) of the [99mTc]Tc-MAG3 preparation. Recently, the Summary of Product Characteristics (SPC) of NephroMAG, a kit dedicated to [99mTc]Tc-MAG3 preparation, proposed a two-strip thin layer chromatography (TLC) based quality control (QC) method. Also, Straub et al recently proposed another TLC based QC method. We sought to evaluate the transferability of these QC methods in our hospital radiopharmacy and compared them to our currently employed TLC method and radio-HPLC (high-pressure liquid chromatography) to select the most appropriate in the context of hospital radiopharmacy. METHODS: Ten consecutive [99mTc]Tc-MAG3 preparations were controlled using: HPLC combined with a radiodetector (radio-HPLC), a single strip TLC method (method 1) in current use in our centre, a two-strip TLC method described in the SPC (method SPC) and a two-strip TLC method (method 2) described by Straub et al. Quantitative results for the four tested QC methods were measured and compared in terms of RCP (%), sodium pertechnetate ([99mTc]TcO4 -) (%) and duration of analysis (min). RESULTS: RCP was significantly different between method SPC and radio-HPLC (p<0.001) and method 2 (p<0.001). Also, the percentage of [99mTc]TcO4 - was statistically different between the radio-HPLC and the method SPC (p<0.001), but not with the method 1 and method 2 group (p>0.05). The duration of analysis (min) was significantly different between the four QC procedures (p<0.001) with method 2 and method SPC being the quickest. CONCLUSIONS: Our study showed it is possible to transfer and select a quick and reliable QC method for the preparation of NephroMAG kits in our centre. We therefore advise the widespread use of the method from Straub et al in hospital radiopharmacies.

68 Ga-Prostate-Specific Membrane Antigen PET/CT in Ovarian Tumors : Potential to Differentiate Benign and Malignant Tumors Before Surgery: A Preliminary Report.

PURPOSE OF THE REPORT: Ovarian cancer is usually diagnosed in an advanced stage of disease due to the absence of specific symptoms and a lack of sensitive diagnostic methods. Prostate-specific membrane antigen (PSMA) is expressed on prostate cancer cells but can be found in other tumors such as ovarian cancer.The aim of this pilot study was to evaluate the feasibility of using 68 Ga-PSMA-11 PET/CT in detection of ovarian neoplasm before surgical treatment. PATIENTS AND METHODS: Eight women with mean age of 56.0 ± 16.2 years were included in the study. All patients underwent transvaginal ultrasound followed by CT scan of the chest and abdomen as qualification for surgery. Within a 1-week interval, PET/CT was performed on a Siemens Biograph scanner, 60 minutes after injection of 2 MBq/kg 68 Ga-PSMA-11. RESULTS: In 3 cases (37.5%), the 68 Ga-PSMA-11 PET/CT was positive, whereas histological examination confirmed 2 serous ovarian cancer cases and 1 ovarian borderline tumor. The SUV max in the serous ovarian cancer was 8.7 and 4.1, and in the borderline ovarian tumor, it was 13.8. No correlation was found between antigen CA-125 level and 68 Ga-PSMA expression. Range of tumor SUV max was not correlated with stage of disease. The remaining 62.5% (5/8) were negative in 68 Ga-PSMA-11 PET/CT, and histopathology confirmed benign pelvic tumor. CONCLUSIONS: The initial experience supports the potential to use 68 Ga-PSMA-11 in ovarian cancer to differentiate malignant and benign tumors before surgery.This study was approved by the Ethical Committee of the Medical University of Warsaw (KB/2/A/2018).

Development and Validation of an Analytical HPLC Method to Assess Chemical and Radiochemical Purity of [68Ga]Ga-NODAGA-Exendin-4 Produced by a Fully Automated Method.

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in pancreatic islets, especially in ß-cells, and highly expressed in human insulinomas and gastrinomas. In recent years several GLP-1R-avid radioligands have been developed to image insulin-secreting tumors or to provide a tentative quantitative in vivo biomarker of pancreatic ß-cell mass. Exendin-4, a 39-amino acid peptide with high binding affinity to GLP-1R, has been labeled with Ga-68 for imaging with positron emission tomography (PET). Preparation conditions may influence the quality and in vivo behavior of tracers. Starting from a published synthesis and quality controls (QCs) procedure, we have developed and validated a new rapid and simple UV-Radio-HPLC method to test the chemical and radiochemical purity of [68Ga]Ga-NODAGA-exendin-4, to be used in the clinical routine. Methods: Ga-68 was obtained from a 68Ge/68Ga Generator (GalliaPharma®) and purified using a cationic-exchange cartridge on an automated synthesis module (Scintomics GRP®). NODAGA-exendin-4 contained in the reactor (10 µg) was reconstituted with HEPES and ascorbic acid. The reaction mixture was incubated at 100 °C. The product was purified through HLB cartridge, diluted, and sterilized. To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document released by the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. Therefore, a range of concentrations of Ga-NODAGA-exendin-4, NODAGA-exendin-4 (5, 4, 3.125, 1.25, 1, and 0.75 µg/mL) and [68Ga]Ga-NODAGA-exendin-4 were analyzed. To validate the entire production process, three consecutive batches of [68Ga]Ga-NODAGA-exendin-4 were tested. Results: Excellent linearity was found between 5-0.75 µg/mL for both the analytes (NODAGA-exendin-4 and 68Ga-NODAGA-exendin-4), with a correlation coefficient (R2) for calibration curves equal to 0.999, average coefficients of variation (CV%) < 2% (0.45% and 0.39%) and average per cent deviation value of bias from 100%, of 0.06% and 0.04%, respectively. The calibration curve for the determination of [68Ga]Ga-NODAGA-exendin-4 was linear with a R2 of 0.993 and CV% < 2% (1.97%), in accordance to acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed using 10 µg of peptide. The mean radiochemical yield was 45 ± 2.4% in all the three validation batches of [68Ga]Ga-NODAGA-exendin-4. The radiochemical purity of [68Ga]Ga-NODAGA-exendin-4 was >95% (97.05%, 95.75% and 96.15%) in all the three batches. Conclusions: The developed UV-Radio-HPLC method to assess the radiochemical and chemical purity of [68Ga]Ga-NODAGA-exendin-4 is rapid, accurate and reproducible like its fully automated production. It allows the routine use of this PET tracer as a diagnostic tool for PET imaging of GLP-1R expression in vivo, ensuring patient safety.

Utility of 18F-FDG-PET for detecting acute lymphoblastic leukemia: a case series of pediatric acute lymphoblastic leukemia without hematological symptoms.

Acute leukemia is typically diagnosed from presenting features related to hematological symptoms, but certain patients present with prominent musculoskeletal pain without signs of hematological abnormality. We reviewed the medical records of 58 children diagnosed with acute lymphoblastic leukemia (ALL) at our hospital to evaluate initial features. Forty six of these patients had hematological symptoms, anemia, or hemorrhage (Group H), while 12 patients had prominent musculoskeletal pain without hematological symptoms (Group P). Diagnosis of leukemia took significantly more time for those 12 patients (Group H, 17.1 days; Group P, 48.5 days). In three of the 12 patients in Group P, localized abnormal imaging findings and unremarkable blood test results led to initial diagnoses of chronic recurrent multifocal osteomyelitis, bone fracture, and septic osteomyelitis. However, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) revealed multiple intense bone foci or systemic bone marrow uptake, leading to the diagnosis of ALL. A review of 18F-FDG-PET results from 23 patients with ALL who underwent a PET scan (Group H, n = 15; Group P, n = 8) showed multiple bone foci or systemic bone marrow uptake in all cases. In conclusion, lack of hematological symptoms in ALL patients can delay diagnosis, and 18F-FDG-PET is useful for diagnosing leukemia in such cases.

A generic gas chromatography method for determination of residual solvents in PET radiopharmaceuticals.

A novel gas chromatography (GC) method for quantitation of volatile organic compounds (VOCs) in 18F- and 11C-radiopharmaceuticals listed in the European Pharmacopoeia (Ph. Eur.) was proposed. Optimized chromatographic parameters were used for separation of ethanol, acetone, acetonitrile, tetrahydrofuran (THF), dibromomethane (DBM), 2-dimethylaminoethanol (deanol), N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) which could be detected in radioactive drug samples. The calculated peak resolutions (RS) were higher than 2.0 at ethanol concentration of up to 11 m/m%. Reproducible results could be obtained using base deactivated fused silica wool as packing material of inlet liner. Validation parameters showed excellent linearity (r2 ≥0.9998) in the range from 10 to at least 120% of concentration limit of solvents. The accuracy was determined as recovery of concentrations which ranged from 99.3% to 103.8%. Additionally, the relative standard deviation (RSD) of each solvent for inter-day and intra-day precision were in the range of 0.5-4.2% and 0.4-4.4%, respectively. The limit of quantitation (LOQ) for ethanol, acetone, acetonitrile, THF, DBM, deanol, DMF and DMSO was 0.48, 0.42, 0.43, 0.46, 4.35, 0.73, 0.68 and 0.50 mg/L, respectively. The developed procedure was successively applied for quantitation of ethanol, acetone, acetonitrile and deanol in radioactive drug samples of [11C]methionine, [11C]choline, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET). The proposed GC method applying flame ionization detection (FID) could be adapted in routine quality control of most frequently used positron emission tomography (PET) radiopharmaceuticals to perform the determination of residual solvents with analysis time of 12 min.

Potential of [11C]UCB-J as a PET tracer for islets of Langerhans.

Biomarkers for the measurement of islets of Langerhans could help elucidate the etiology of diabetes. Synaptic vesicle glycoprotein 2 A (SV2A) is a potential marker reported to be localized in the endocrine pancreas. [11C]UCB-J is a novel positron emission tomography (PET) radiotracer that binds to SV2A and was previously evaluated as a synaptic marker in the central nervous system. Here, we evaluated whether [11C]UCB-J could be utilized as a PET tracer for the islets of Langerhans in the pancreas by targeting SV2A. The mRNA transcription of SV2A was evaluated in human isolated islets of Langerhans and exocrine tissue. In vitro autoradiography was performed on pancreas and brain sections from rats and pigs, and consecutive sections were immunostained for insulin. Sprague-Dawley rats were examined with PET-MRI and ex vivo autoradiography at baseline and with administration of levetiracetam (LEV). Similarly, pigs were examined with dynamic PET-CT over the pancreas and brain after administration of [11C]UCB-J at baseline and after pretreatment with LEV. In vivo radioligand binding was assessed using a one-compartment tissue model. The mRNA expression of SV2A was nearly 7 times higher in endocrine tissue than in exocrine tissue (p < 0.01). In vitro autoradiography displayed focal binding of [11C]UCB-J in the pancreas of rats and pigs, but the binding pattern did not overlap with the insulin-positive areas or with ex vivo autoradiography. In rats, pancreas binding was higher than that in negative control tissues but could not be blocked by LEV. In pigs, the pancreas and brain exhibited accumulation of [11C]UCB-J above the negative control tissue spleen. While brain binding could be blocked by pretreatment with LEV, a similar effect was not observed in the pancreas. Transcription data indicate SV2A to be a valid target for imaging islets of Langerhans, but [11C]UCB-J does not appear to have sufficient sensitivity for this application.

[18F]Atorvastatin Pharmacokinetics and Biodistribution in Healthy Female and Male Rats.

Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that are widely used to prevent cardiovascular diseases. However, a series of pleiotropic mechanisms have been associated with statins, particularly with atorvastatin. Therefore, the assessment of [18F]atorvastatin kinetics with positron emission tomography (PET) may elucidate the mechanism of action of statins and the impact of sexual dimorphism, which is one of the most debated interindividual variations influencing the therapeutic efficacy. [18F]Atorvastatin was synthesized via a previously optimized 18F-deoxyfluorination strategy, used for preclinical PET studies in female and male Wistar rats (n = 7 for both groups), and for subsequent ex vivo biodistribution assessment. PET data were fitted to several pharmacokinetic models, which allowed for estimating relevant kinetic parameters. Both PET imaging and biodistribution studies showed negligible uptake of [18F]atorvastatin in all tissues compared with the primary target organ (liver), excretory pathways (kidneys and small intestine), and stomach. Uptake of [18F]atorvastatin was 38 ± 3% higher in the female liver than in the male liver. The irreversible 2-tissue compartment model showed the best fit to describe [18F]atorvastatin kinetics in the liver. A strong correlation (R2 > 0.93) between quantitative Ki (the radiotracer's unidirectional net rate of influx between compartments) and semi-quantitative liver's SUV (standard uptake value), measured between 40 to 90 min, showed potential to use the latter parameter, which circumvents the need for blood sampling as a surrogate of Ki for monitoring [18F]atorvastatin uptake. Preclinical assays showed faster uptake and clearance for female rats compared to males, seemingly related to a higher efficiency for exchanges between the arterial input and the hepatic tissue. Due to the slow [18F]atorvastatin kinetics, equilibrium between the liver and plasma concentration was not reached during the time frame studied, making it difficult to obtain sufficient and accurate kinetic information to quantitatively characterize the radiotracer pharmacokinetics over time. Nevertheless, the reported results suggest that the SUV can potentially be used as a simplified measure, provided all scans are performed at the same time point. Preclinical PET-studies with [18F]atorvastatin showed faster uptake and clearance in female compared to male rats, apparently related to higher efficiency for exchange between arterial blood and hepatic tissue.

A survey among German-speaking radiation oncologists on PET-based radiotherapy of prostate cancer.

BACKGROUND: Positron emission tomography-(PET) has evolved as a powerful tool to guide treatment for prostate cancer (PC). The aim of this survey was to evaluate the acceptance and use of PET-especially with prostate-specific membrane antigen (PSMA) targeting tracers-in clinical routine for radiotherapy (RT) and the impact on target volume definition and dose prescription. METHODS: We developed an online survey, which we distributed via e-mail to members of the German Society of Radiation Oncology (DEGRO). The survey included questions on patterns of care of RT for PC with/without PET. For evaluation of doses we used the equivalent dose at fractionation of 2 Gy with α/ß = 1.5 Gy [EQD2(1.5 Gy)]. RESULTS: From 109 participants, 78.9% have the possibility to use PET for RT planning. Most centers use PSMA-targeting tracers (98.8%). In 39.5%, PSMA-PET for biochemical relapse after prior surgery is initiated at PSA ≥ 0.5 ng/mL, while 30.2% will perform PET at ≥ 0.2 ng/mL (≥ 1.0 ng/mL: 16.3%, ≥ 2.0 ng/mL: 2.3%, regardless of PSA: 11.7%). In case of PET-positive local recurrence (LR) and pelvic lymph nodes (LNs), 97.7% and 96.5% of the participants will apply an escalated dose. The median total dose in EQD2(1.5 Gy) was 70.00 Gy (range: 56.89-85.71) for LR and 62.00 Gy (range: 52.61-80.00) for LNs. A total number of ≤ 3 (22.0%) or ≤ 5 (20.2%) distant lesions was most often described as applicable for the definition as oligometastatic PC. CONCLUSION: PSMA-PET is widely used among German radiation oncologists. However, specific implications on treatment planning differ among physicians. Therefore, further trials and guidelines for PET-based RT are warranted.

Longitudinal evaluation of a novel BChE PET tracer as an early in vivo biomarker in the brain of a mouse model for Alzheimer disease.

Purpose: The increase in butyrylcholinesterase (BChE) activity in the brain of Alzheimer disease (AD) patients and animal models of AD position this enzyme as a potential biomarker of the disease. However, the information on the ability of BChE to serve as AD biomarker is contradicting, also due to scarce longitudinal studies of BChE activity abundance. Here, we report 11C-labeling, in vivo stability, biodistribution, and longitudinal study on BChE abundance in the brains of control and 5xFAD (AD model) animals, using a potent BChE selective inhibitor, [11C]4, and positron emission tomography (PET) in combination with computerised tomography (CT). We correlate the results with in vivo amyloid beta (Aß) deposition, longitudinally assessed by [18F]florbetaben-PET imaging. Methods: [11C]4 was radiolabelled through 11C-methylation. Metabolism studies were performed on blood and brain samples of female wild type (WT) mice. Biodistribution studies were performed in female WT mice using dynamic PET-CT imaging. Specific binding was demonstrated by ex vivo and in vivo PET imaging blocking studies in female WT and 5xFAD mice at the age of 7 months. Longitudinal PET imaging of BChE was conducted in female 5xFAD mice at 4, 6, 8, 10 and 12 months of age and compared to age-matched control animals. Additionally, Aß plaque distribution was assessed in the same mice using [18F]florbetaben at the ages of 2, 5, 7 and 11 months. The results were validated by ex vivo staining of BChE at 4, 8, and 12 months and Aß at 12 months on brain samples. Results: [11C]4 was produced in sufficient radiochemical yield and molar activity for the use in PET imaging. Metabolism and biodistribution studies confirmed sufficient stability in vivo, the ability of [11C]4 to cross the blood brain barrier (BBB) and rapid washout from the brain. Blocking studies confirmed specificity of the binding. Longitudinal PET studies showed increased levels of BChE in the cerebral cortex, hippocampus, striatum, thalamus, cerebellum and brain stem in aged AD mice compared to WT littermates. [18F]Florbetaben-PET imaging showed similar trend of Aß plaques accumulation in the cerebral cortex and the hippocampus of AD animals as the one observed for BChE at ages 4 to 8 months. Contrarily to the results obtained by ex vivo staining, lower abundance of BChE was observed in vivo at 10 and 12 months than at 8 months of age. Conclusions: The BChE inhibitor [11C]4 crosses the BBB and is quickly washed out of the brain of WT mice. Comparison between AD and WT mice shows accumulation of the radiotracer in the AD-affected areas of the brain over time during the early disease progression. The results correspond well with Aß accumulation, suggesting that BChE is a promising early biomarker for incipient AD.

The development and validation of a high performance liquid chromatography method to determine the radiochemical purity of [177Lu]Lu-HA-DOTA-TATE in pharmaceutical preparations.

Lutetium-177 [177Lu] tetra-azacyclododecanetetra-acetic acid [DOTA]-(Tyr3)-octreotate [TATE] ([177Lu]Lu-DOTA-TATE) is a radiopeptide used for peptide receptor radionuclide therapy in patients with neuroendocrine tumours (NETs). This radiopeptide is made by labelling the ligand octreotate with Lutetium-177 using the linker DOTA. After labelling, and before clinical application quality control of the radiopeptide is needed and the radiochemical purity is assessed. Acceptance limits for radiochemical purity should be within 90-110% of the label claim for radiopharmaceuticals for diagnostic use and within 95-105% of the label claim for radiopharmaceuticals for therapeutic use. Moreover, the amount of unlabelled [177Lu]LuCl3 cannot exceed 2% of the radioactive dose. Since no monograph is available for [177Lu]Lu-DOTA-TATE in the European Pharmacopeia (Ph Eur), this article describes the development and validation of a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection and radiodetection. A Waters Acquity Arc UHPLC system equipped with a Waters 2998 photodiode array (PDA) detector was used coupled to a Berthold Lb 514 Flowstar detector equipped with a BGO-X gamma measuring cell. A reversed phase Symmetry Shield C18 column (4.6 mm × 250 mm, 5 µm) was used for chromatographic separation. A flow of 1.5 mL/min was maintained during analysis, using 0.1% TFA in water as mobile phase A and 0.1% TFA in ACN as mobile phase B. The retention time was around 1.7 min and 13.5 min for [177Lu]LuCl3 and [177Lu]Lu-HA-DOTA-TATE, respectively. Stock solutions of [177Lu]LuCl3 were made by serial dilution and were injected to test for linearity, accuracy and precision, carry over and signal-to-noise ratio. A [177Lu]Lu-HA-DOTA-TATE sample was prepared and injected to determine the carry over. The results showed that the method is linear over a range of 0.300-130 MBq/mL, which covers the range for clinical samples, provided that the clinical sample is diluted ten times before analysis. The LLOQ can be measured accurately even after dilution, with a signal-to-noise ratio of at least 5. In short, the method is accurate, precise and sensitive and can be implemented as part of the quality control of [177Lu]Lu-HA-DOTA-TATE.

Synthesis and Initial Characterization of a Reversible, Selective 18F-Labeled Radiotracer for Human Butyrylcholinesterase.

PURPOSE: A neuropathological hallmark of Alzheimer's disease (AD) is the presence of amyloid-ß (Aß) plaques in the brain, which are observed in a significant number of cognitively normal, older adults as well. In AD, butyrylcholinesterase (BChE) becomes associated with Aß aggregates, making it a promising target for imaging probes to support diagnosis of AD. In this study, we present the synthesis, radiochemistry, in vitro and preliminary ex and in vivo investigations of a selective, reversible BChE inhibitor as PET-tracer for evaluation as an AD diagnostic. PROCEDURES: Radiolabeling of the inhibitor was achieved by fluorination of a respective tosylated precursor using K[18F]. IC50 values of the fluorinated compound were obtained in a colorimetric assay using recombinant, human (h) BChE. Dissociation constants were determined by measuring hBChE activity in the presence of different concentrations of inhibitor. RESULTS: Radiofluorination of the tosylate precursor gave the desired radiotracer in an average radiochemical yield of 20 ± 3 %. Identity and > 95.5 % radiochemical purity were confirmed by HPLC and TLC autoradiography. The inhibitory potency determined in Ellman's assay gave an IC50 value of 118.3 ± 19.6 nM. Dissociation constants measured in kinetic experiments revealed lower affinity of the inhibitor for binding to the acylated enzyme (K2 = 68.0 nM) in comparison to the free enzyme (K1 = 32.9 nM). CONCLUSIONS: The reversibly acting, selective radiotracer is synthetically easily accessible and retains promising activity and binding potential on hBChE. Radiosynthesis with 18F labeling of tosylates was feasible in a reasonable time frame and good radiochemical yield.

Supplemental minimal-activity PET/CT to validate ambiguous findings with less than 1 mSv: Proof of concept.

Short-term follow-up examinations could verify ambiguous findings in PET/CT diagnostics, but are often avoided due to radiation and financial burdens. We demonstrate the feasibility of a focused, minimal-activity PET protocol as a supplemental examination for uncertain findings after standard PET/CT. After changing conditions, e.g. patient positioning, preparation and bypassing an interval as well as a targeted tracer change, an additional examination with less than 1 mSv of additional radiation exposure was performed. Lowered administered activity of radiopharmaceuticals could be compensated by prolonged acquisition time, which was made possible by the limitation to a single body region. A sufficient visual and quantitative image quality of scans could be achieved. In all cases, the ambiguous finding could be clarified, so further diagnostic procedures or unnecessary interventions were avoided.

Ambient and personnel occupational dose assessment in a Hospital's PET/CT center.

This study used thermoluminescent dosimeters (TLDs) to measure cumulative radiation doses in a PET/CT center. It covered 18 areas and four personnel groups. Because the isolated lead shielding separated the patients from the nurses, wearing protective clothing when injecting radiopharmaceuticals was unnecessary. Fingertip doses of the dispensing and nurse groups were below the occupational limit. Current radiopharmaceutical transportation and injection operations in this PET/CT center provide considerable radiation protection to medical personnel.

Extremity Exposure with 99mTc - Labelled Radiopharmaceuticals in Diagnostic Nuclear Medicine.

BACKGROUND: Extremity exposures may raise the risk of cancer induction among radiographers involved in the preparation and administration of technetium-99m labelled radiopharmaceuticals. OBJECTIVE: To estimate finger doses on radiographers at a South African tertiary hospital. METHODS: Adhesive tape was used to securely fix a calibrated thermoluminescent dosimeter (TLD) on fingertips and bases of ring and index fingers of both hands of five radiographers who prepared and administered technetium-99m labelled radiopharmaceuticals. Rubber gloves were worn to avoid TLD contamination. TLDs doses were read with a Harsaw TLD Reader (Model 3500) after a week. RESULTS: Five radiographers prepared and administered technitium-99m labelled radiopharmaceuticals (activity range; 78.20 GBq - 132.78 GBq during a one-week measurement period). A radiographer handling 132.78 GBq received 4.74±0.52 mSv on both hands; 5.52, 4.55, 5.11 and 4.60 mSv on the fingertip of the index finger of the dominant hand (FIDH), fingertip of the ring finger of the dominant hand (FRDH), fingertip of the index finger of the non-dominant hand (FINDH) and fingertip of the ring finger of the non-dominant hand (FRNDH), respectively. The respective doses received on the finger bases were 4.50 mSv, 4.60, 4.21 and 3.48 mSv. The radiographer handling 78.20 GBq received 0.85±0.18 mSv on both hands, 1.04, 1.17, 0.77 and 1 mSv for the FIDH, FRDH, FINDH and FRNDH, respectively, while respective doses for the bases were 0.8, 0.9, 0.6 and 0.8 mSv. CONCLUSION: The extremity exposures were below the annual limit (500 mSv). However, the use of syringe shields could still reduce the finger doses further.

Analytical GC-FID Method for the Determination of Organic Solvents in Radiopharmaceuticals.

BACKGROUND: Organic solvents play an indispensable role in most of the radiopharmaceutical production stages. It is almost impossible to remove them entirely in the final formulation of the product. OBJECTIVE: In this presented work, an analytical method by gas chromatography coupled with flame ionization detection (GC-FID) has been developed to determine organic solvents in radiopharmaceutical samples. The effect of injection holding time, temperature variation in the injection port, and the column temperature on the analysis time and resolution (R ≥ 1.5) of ethanol and acetonitrile was studied extensively. METHODS: The experimental conditions were optimized with the aid of further statistical analysis; thence, the proposed method was validated following the International Council for Harmonisation (ICH) Q2 (R1) guideline. RESULTS: The proposed analytical method surpassed the acceptance criteria including the linearity > 0.990 (correlation coefficient of R2), precision < 2%, LOD, and LOQ, accuracy > 90% for all solvents. The separation between ethanol and acetonitrile was acceptable with a resolution R > 1.5. Further statistical analysis of Oneway ANOVA revealed that the increment in injection holding time and variation of temperature at the injection port did not significantly affect the analysis time. Nevertheless, the variation in injection port temperature substantially influenced the resolution of ethanol and acetonitrile peaks (p < 0.05). CONCLUSION: The proposed analytical method has been successfully implemented to determine the organic solvent in the [18F]fluoro-ethyl-tyrosine ([18F]FET), [18F]fluoromisonidazole ([18F]FMISO), and [18F]fluorothymidine ([18F]FLT).

Cellular S-value evaluation based on real human cell models using the GATE MC package.

Exploring the spatial distribution of the energy loss of ionising radiation at the subcellular level is indispensable for evaluating the radiobiological effects of targeted radionuclide therapy accurately. Believing that S-values are important for obtaining the target dose, the Committee on Medical Internal Radiation Dose (MIRD) proposed a method to obtain the cellular dosimetric parameter. However, most available data on cellular S-values were calculated based on simple geometric models, such as ellipsoids or spheres, which do not accurately reflect biological reality. To investigate the influence of the cellular model on S-values, calculations were performed for two kinds of polygon-surface phantom models of realistic, individual human cells, the lung epithelial cell model (the B2B Phantom model) and the hepatocyte model (the Liver Phantom model), using the Monte Carlo (MC) software package GATE. To analyse the influence of cell geometry on the final S-value, the differences in the S-values between the realistic cell models and simple geometric sphere and ellipsoid models with similar volumes were calculated and compared for six different combinations of source and target regions. The irradiation conditions were 0.01-1.10 MeV monoenergetic electron sources and the Auger electronic therapy nuclides Ga-67, Tc-99m, In-111, I-125 and Tl-201, which are commonly used in nuclear medicine. The S-values calculated in this study are different from the results of the simple geometry models proposed by previous researchers. Two more precise polygon-surface phantom models of realistic, individual human cells were used, which provided more accurate information about the cell dose and will be very useful for the diagnostic application of radiotherapy in the future.

Investigation of the new non-invasive semi-quantitative method of 123I-IMP pediatric cerebral perfusion SPECT.

In pediatric cases requiring quantification of cerebral blood flow (CBF) using 123I-N-isopropyl-p-iodoamphetamine (123I-IMP) single-photon emission computed tomography (SPECT), arterial blood sampling is sometimes impossible due to issues such as movement, crying, or body motion. If arterial blood sampling fails, quantitative diagnostic assessment becomes impossible despite radiation exposure. We devised a new easy non-invasive microsphere (e-NIMS) method using whole-body scan data. This method can be used in conjunction with autoradiography (ARG) and can provide supportive data for invasive CBF quantification. In this study, we examined the usefulness of e-NIMS for pediatric cerebral perfusion semi-quantitative SPECT and compared it with the invasive ARG. The e-NIMS estimates cardiac output (CO) using whole-body acquisition data after 123I-IMP injection and the body surface area from calculation formula. A whole-body scan was performed 5 minutes after the 123I-IMP injection and CO was estimated by region of interest (ROI) counts measured for the whole body, lungs, and brain using the whole-body anterior image. The mean CBF (mCBF) was compared with that acquired via ARG in 115 pediatric patients with suspected cerebrovascular disorders (age 0-15 years). Although the mCBF estimated by the e-NIMS indicated a slight deviation in the extremely low- or high-mCBF cases when compared with the values acquired using the invasive ARG, there was a good correlation between the two methods (r = 0.799; p < 0.001). There were no significant differences in the mCBF values based on physical features, such as patients' height, weight, and age. Our findings suggest that 123I-IMP brain perfusion SPECT with e-NIMS is the simplest semi-quantitative method that can provide supportive data for invasive CBF quantification. This method may be useful, especially in pediatric brain perfusion SPECT, when blood sampling or identifying pulmonary arteries for CO estimation using the graph plot method is difficult.

Attenuation of Gamma Radiation Using ClearView Radiation ShieldingTM in Nuclear Power Plants, Hospitals and Radiopharmacies.

Radiation protection materials, such as lead (Pb), water, concrete, steel, and aluminum, have been successfully used for decades. Although they are effective shields, these materials do have limitations. For example, lead is heavy and toxic, and water and concrete must be thick to provide significant shielding, all of which renders these materials prohibitive for certain applications. For example, the half-value layer for water to shield against Co is 30.48 cm (12"), which makes it an extremely bulky material. The development of ClearView Radiation Shielding addresses some of the limitations that are faced by traditional radiation protection shields. The product is a transparent liquid gamma radiation shield that can be fabricated in custom sizes and thicknesses. Here, we describe applications of ClearView Radiation Shielding in nuclear plants and hospitals. ClearView Radiation Shielding is used to shield nuclear power plant workers from Co in critical path and high dose in refueling outages to observe automated operations inside the containment, and operations such as cylindrical frisking stations and benchtop sampling. ClearView Radiation Shielding is designed as rolling shields and radionuclide containments in hospitals to protect staff and families during unsealed radionuclide treatment such as MIBG and Lutetium therapies. For successful implementation in hospitals, the product was tested against various radioisotopes, also described in this work. Operational uses of ClearView Radiation Shielding in commercial nuclear and medical industries allows staff working in radioactive environments visibility, better communication and similar levels of radiation protection compared with traditional shielding materials. The product helps improve workflows and reduced total dose received by workers. Additionally, attenuation measurements using ClearView Radiation Shielding against multiple isotopes was performed. With 1.25 cm (0.5") ClearView Radiation Shielding thickness, the shield attenuated 1) 65% of the effective dose from I, 2) 35.15% of the effective dose from Cs, and 3) 22.5% of the effective dose from Co. Isotopes in the range of 35 keV to 1899 keV. 3.81 were attenuated greater than 90% with a ClearView Radiation Shielding shield thickness of 7.62 cm (3"). The half-value layer for Co with a ClearView Radiation Shielding thickness of 3.81 cm (1.5") attenuated the effective dose of F gammas by 85.59%. With a density of 2.3 g cm, ClearView Radiation Shielding was measured to be half the weight of lead for equal shielding. ClearView Radiation Shielding is transparent, lightweight, and an alternative material to conventional radiation shields to reduce radiation exposure.

Radionuclide calibrator intercomparison study of clinical PET centres in England to a single traceable 68Ge syringe source.

OBJECTIVES: The aim of this study was to characterize national variation in radionuclide calibrator activity response to a single National Institute of Standards and Technology (NIST) traceable reference Ge source used as a surrogate for F at clinical PET centres in England using National Physical Laboratory approved techniques. METHODS: Readings from 20 instruments at 13 centres using local F and Ge factor settings were recorded with the source located in vial and syringe positions. Ten repeat measurements were conducted to investigate repeatability using % coefficient of variability (COV). Comparison ratios to investigate accuracy were made between calibrator responses and decay-corrected NISTref reference activity for syringe and vial position measurements. RESULTS: The maximum %COV was 0.79%, while 90, 95 and 80% of calibrators conformed to 5% accuracy for F syringe, Ge syringe and Ge vial position readings, respectively. We revealed a trend towards reduced bias in measurements using Veenstra devices for F and using Capintec devices for Ge factor settings. CONCLUSIONS: This study demonstrated good repeatability in local device measurements. In total, 70% of English calibrators tested and 88% of all measurements performed achieved 5% accuracy. While statistically significant bias was exhibited between different vendor equipment dependent upon radioisotope selected, our study recommends regular traceability checks for optimum instrument performance conducted within National Metrology Institutes guidelines.