68Ga-Labelled Carbon Nanoparticles for Ventilation PET/CT Imaging: Physical Properties Study and Comparison with Technegas®.

PURPOSE: The use of 68Ga-labelled carbon nanoparticles has been proposed for lung ventilation PET/CT imaging. However, no study has assessed the physical properties of 68Ga-labelled carbon nanoparticles. The aim of this study therefore was to evaluate the shape and size of 68Ga-labelled carbon nanoparticles, and to determine the composition of the aerosol, as opposed to 99mTc-labelled carbon nanoparticles aerosol. PROCEDURES: 99mTc- and 68Ga-labelled carbon nanoparticles, stable gallium carbon nanoparticles, 0.9 % NaCl and 0.1 N HCl-based carbon nanoparticles were produced using an unmodified Technegas® generator, following the usual technique used for clinical Technegas® production. The shape and size of particles were studied by transmission electron microscopy (TEM) after decay of the radioactive samples. The composition of the 68Zn- and 99Tc-labelled carbon nanoparticles aerosols was assessed using scanning electron microscopy (SEM) coupled with energy dispersive X-ray (EDX) analysis after decay of the 68Ga- and 99mTc-labelled carbon nanoparticles, respectively. RESULTS: On TEM, all samples showed similar shape with hexagonally structured primary particles, agglomerated in clusters. The mean diameters of primary stable gallium carbon nanoparticles, 99Tc- and 68Zn-labelled carbon nanoparticles were 22.4 ± 10 nm, 20.9 ± 7.2 nm and 19.8 ± 11.7 nm, respectively. CONCLUSION: Using Technegas® generator in the usual clinical way, 99mTc- and 68Ga-labelled carbon nanoparticles demonstrated similar shape and diameters in the same size range size. These results support the use of 68Ga-labelled carbon nanoparticles for the assessment of regional lung ventilation function with PET imaging.

Clinical Efficacy of Sodium [99mTc] Pertechnetate from Low Specific Activity 99Mo/99mTc Autosolex Generator in Hospital Radiopharmacy Centre.

BACKGROUND: Few nuclear reactors in the world producing high specific activity (HSA) 99Mo using enriched 235U (HEU), are aging and are planned for shut down in the near future. Further, HEU will not be freely available, due to safeguards, and the technology for 99Mo from low-enriched 235U (LEU) is not yet widely accepted since 239Pu contamination in the product is an issue. Production of 99mTc from low specific activity (LSA) 99Mo obtained from 98Mo(n,)99Mo reaction in research reactor and 100Mo(,n)99Mo reaction in accelerator or directly from 100Mo(p,2n)99mTc nuclear reaction in cyclotron, has been explored [1]. The methyl ethyl ketone (MEK) based solvent extraction technique is n well known method for the separation of 99mTc from low specific activity 99Mo. The 99Mo/99mTc autosolex generator [2], a computer controlled automated module, utilizes the conventional MEK solvent extraction method for extraction of 99mTc. Herein, we have validated the usage of autosolex for preparation of pharmacopoeia grade 99mTcO4- from 7.40-27.5 GBq of LSA 99Mo-SodiumMolybdate (99MoO42-) solution and validated the quality of the 99mTcO4- by preparing wide range of 99mTc-radiopharmaceuticals (99mTc-RP). MATERIALS AND METHODS: The 99mTcO4- was extracted from the autosolex as described in [2] starting from 7.40-27.5 GBq of LSA 99MoO42- and subjected to the required physico-chemical and biological quality control (QC) tests. The eluted 99mTcO4- labeled various fourth generation 99mTc radiopharmaceuticals cold kits (99mTc-cold kits) apart from regular 99mTc-cold kits in our centre. Various 99mTc-RP extracted 99mTcO4- using standard procedures [3] were prepared and subjected to required QC as Indian Pharmacopeia monograph [4] and used in scintigraphic imaging in patients. The radiation exposure dose to the operator were compared between autosolex and manual MEK based solvent extraction generator. RESULTS: The extracted 99mTcO4- from autosolex is a clear and colorless solution with pH between 5.0-6.5. The elemental molybdenum (Mo) and aluminum (Al) content <10µg/mL, MEK levels <0.1%, 99Mo breakthrough <0.030% and radiochemical purity (RCP) >98%. All the extracted 99mTcO4- batches complies sterility test, endotoxin limit (EL) <5EU/mL. The RCP of all the labeled 99mTc-RP >95%. The autosolex delivers much less radiation dose to the operator than the convention manually handled MEK based solvent extraction generator. CONCLUSIONS: Autosolex Generator was successfully used to obtain pharmaceutical grade 99mTcO4- from LSA 99MoO42- and generator is safe in radiological and pharmacological point of view. The suitability of the autosolex for use in hospital radiopharmacy was shown by using the 99mTcO4- to prepare various 99mTc-RP and using these 99mTc-RP for scintigraphic imaging in patients.

Potential Applications of 68Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with 99mTcO4 - Salivary Gland Scintigraphy.

Purpose: To preliminarily evaluate the feasibility and potential of using 68Ga-PSMA-11 PET/CT in evaluating the function of salivary glands and lacrimal glands in comparison with 99mTc-pertechnetate (99mTcO4 -) salivary gland scintigraphy (SGS). Methods: A retrospective study was performed in 15 patients with different degrees of xerostomia and suspected salivary gland dysfunction. Each patient underwent 68Ga-PSMA-11 PET/CT first and SGS the next day, and the findings of both scans were compared. Results: The results of 68Ga-PSMA-11 PET/CT and SGS were consistent in 12/15 patients (80%) and were inconsistent in the remaining patients (20%). For 5 (33.3%) of 15 patients, 68Ga-PSMA-11 PET/CT provided more information than did SGS. Additionally, 68Ga-PSMA-11 PET/CT corrected the misdiagnosis by SGS for 1 patient. Conclusions: 68Ga-PSMA-11 PET/CT is a potentially useful imaging tool for evaluating the function of salivary glands and lacrimal glands. 68Ga-PSMA-11 PET/CT can be a promising supplement to SGS, and its clinical value deserves further study.

Quantitative evaluation of salivary gland scintigraphy in Sjögren's syndrome: comparison of diagnostic efficacy and relationship with pathological features of the salivary glands.

OBJECTIVE: The value of salivary gland scintigraphy (SGS) in the evaluation of Sjögren's syndrome (SS) remains controversial. The aim of this study was to evaluate the diagnostic efficacy of quantitative SGS in patients with xerostomia and to assess the correlation between scintigraphic parameters and pathological features of salivary glands. METHODS: Medical records of 165 patients with xerostomia who underwent [99mTc] pertechnetate SGS and labial biopsy were retrospectively reviewed. The maximum accumulation ratio (MAR), maximum secretion ratio (MSR), and time interval from stimulation to minimum count (Tmin) of the parotid glands were calculated to quantify the glandular activity. Furthermore, pre-stimulatory oral activity index (PRI) and post-stimulatory oral activity index (POI) were calculated to quantify the oral activity. RESULTS: All parameters except for Tmin were significantly lower in patients with SS than in those without SS. Among the five SGS parameters, PRI showed the highest areas under the curve value (0.9005; p < 0.001), and PRI > 32.75 was associated with a sensitivity of 78.5% and specificity of 86.4% for the diagnosis of SS. A decrease in MAR, MSR, PRI, and POI and an increase in Tmin correlate significantly with the histopathologic grade of labial gland biopsy and disease severity of SS. No significant differences in glandular parameters (MAR, MSR, and Tmin) were found between the non-SS and early-stage SS groups. CONCLUSION: Conventional scintigraphic parameters could be used as simple, reliable, and sensitive indicators for the early diagnosis of SS and determination of disease severity.

Green synthesis of labeled CeO2 nanoparticles with 99mTc and its biodistribution evaluation in mice.

AIMS: The in vivo targeted diagnostic applications of biosynthetic Cerium oxide nanoparticles (CeO2-NPs), prepared by applying chitosan as a stabilizer, was explored by evaluating the cytotoxicity through MTT assay on WEHI 164 cell line, the Hemolytic activity of CeO2-NPs and biodistribution in rats. MAIN METHODS: The CeO2-NPs were characterized through the use of TGA/DTG, PXRD, FESEM, FTIR, and UV-Vis spectroscopy. The biodistribution of CeO2-NPs were determined by directly labeled nanoparticles with Technetium-99 m (99mTc) radioisotope (99mTc-CeO2-NPs). The labeling efficiency and stability of 99mTc-CeO2-NPs were also measured with Instant Thin Layer Chromatography (ITLC) method. The saturation study was investigated by 1 mCi of 99mTc-CeO2-NPs using different concentrations of WEHI 164 cells after 4 h of incubation. In vivo biodistribution study was performed by intravenous injection of 600 µCi/200 µL 99mTc-CeO2-NPs through rat's tail. KEY FINDINGS: CeO2-NPs seemed to have a low cytotoxic effect on WEHI 164 cell line and did not result in hemolysis. The biodistribution of CeO2-NPs has shown that a huge amount of 99mTc-CeO2-NPs was amassed in the living human organs, including liver, lung, spleen, stomach, and thyroid which shows the in vivo stability of the labeled conjugate. Herein, we have developed a facile, economical, and greener synthetic procedure applying Chitosan template. This green approach is comparable to conventional methods that utilize hazardous materials which are would be a suitable alternative to circumvent synthetic issues related to these materials. SIGNIFICANCE: The bio-applications of nano-sized CeO2-NPs were explored to find new horizon to use nanotechnology as the diagnostic tool.

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.

Highly Effective Radioisotope Cancer Therapy with a Non-Therapeutic Isotope Delivered and Sensitized by Nanoscale Coordination Polymers.

Nuclear medicine with radioisotopes is extremely useful for clinical cancer diagnosis, prognosis, and treatment. Herein, polyethylene glycol (PEG)-modified nanoscale coordination polymers (NCPs) composed of hafnium (Hf4+) and tetrakis (4-carboxyphenyl) porphyrin (TCPP) are prepared via a one-pot reaction. By chelation with the porphyrin structure of TCPP, such Hf-TCPP-PEG NCPs could be easily labeled with 99mTc4+, an imaging radioisotope widely used for single-photon emission computed tomography (SPECT) in a clinical environment. Interestingly, Hf, as a high- Z element in such 99mTc-Hf-TCPP-PEG NCPs, could endow nontherapeutic 99mTc with the therapeutic function of killing cancer cells, likely owing to the interaction of Hf with γ rays emitted from 99mTc to produce charged particles for radiosensitization. With efficient tumor retention, as revealed by SPECT imaging, our 99mTc-Hf-TCPP-PEG NCPs offer exceptional therapeutic results in eliminating tumors with moderate doses of 99mTc after either local or systemic administration. Importantly, those biodegradable NCPs could be rapidly excreted without much long-term body retention. Our work, showing the success of applying NCPs for radioisotope therapy (RIT), presents a potential concept for the realization of highly effective cancer treatment with 99mTc, a short-half-life (6.0 h) diagnostic radioisotope, which is promising for cancer RIT with enhanced efficacy and reduced side effects.

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. INTRODUCTION: More 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. METHODS: We 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. RESULTS: High-yield productions with 22 MeV (400 µA, 6 h) yielded an average isolated [99mTc]TcO4- yield of 878 GBq ±â€¯99 GBq (23.7 Ci ±â€¯2.7 Ci) decay corrected to EOB, n = 8 (isolated saturation yield: 4.36 ±â€¯0.49 GBq/µA). Irradiations with 24 MeV (400 µA, 6 h) resulted in an average isolated [99mTc]TcO4- yield of 993 GBq ±â€¯100 GBq (26.8 Ci ±â€¯2.7 Ci) decay corrected to EOB, n = 7 (isolated saturation yield: 4.97 ±â€¯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. CONCLUSION: Reliable near-TBq production yields for 99mTc can be obtained using medium-energy cyclotrons. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This 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.

Novel Application of Quantitative Single-Photon Emission Computed Tomography/Computed Tomography to Predict Early Response to Methimazole in Graves' Disease.

OBJECTIVE: Since Graves' disease (GD) is resistant to antithyroid drugs (ATDs), an accurate quantitative thyroid function measurement is required for the prediction of early responses to ATD. Quantitative parameters derived from the novel technology, single-photon emission computed tomography/computed tomography (SPECT/CT), were investigated for the prediction of achievement of euthyroidism after methimazole (MMI) treatment in GD. MATERIALS AND METHODS: A total of 36 GD patients (10 males, 26 females; mean age, 45.3 ± 13.8 years) were enrolled for this study, from April 2015 to January 2016. They underwent quantitative thyroid SPECT/CT 20 minutes post-injection of 99mTc-pertechnetate (5 mCi). Association between the time to biochemical euthyroidism after MMI treatment and %uptake, standardized uptake value (SUV), functional thyroid mass (SUVmean × thyroid volume) from the SPECT/CT, and clinical/biochemical variables, were investigated. RESULTS: GD patients had a significantly greater %uptake (6.9 ± 6.4%) than historical control euthyroid patients (n = 20, 0.8 ± 0.5%, p < 0.001) from the same quantitative SPECT/CT protocol. Euthyroidism was achieved in 14 patients at 156 ± 62 days post-MMI treatment, but 22 patients had still not achieved euthyroidism by the last follow-up time-point (208 ± 80 days). In the univariate Cox regression analysis, the initial MMI dose (p = 0.014), %uptake (p = 0.015), and functional thyroid mass (p = 0.016) were significant predictors of euthyroidism in response to MMI treatment. However, only %uptake remained significant in a multivariate Cox regression analysis (p = 0.034). A %uptake cutoff of 5.0% dichotomized the faster responding versus the slower responding GD patients (p = 0.006). CONCLUSION: A novel parameter of thyroid %uptake from quantitative SPECT/CT is a predictive indicator of an early response to MMI in GD patients.

Reductive immobilization of pertechnetate in soil and groundwater using synthetic pyrite nanoparticles.

Radioactive technetium (99Tc) is of intense concern because of its toxicity and high mobility in the environment. Reduction of Tc(VII) to Tc(IV) decreases the mobility and availability of technetium in soil and groundwater. In this study, pyrite nanoparticles (FeS2) were synthesized, characterized and tested for immobilizing/removing 99Tc(VII) in soil and groundwater through batch and column experiments. Influences of particle dosage, dissolved organic matter (DOM), and pH on the reductive immobilization kinetics were examined. At a dosage of 0.28 g/L as Fe, the pyrite nanoparticles were able to rapidly and completely remove 4.88 × 10-7 M of Tc(VII) by converting it to insoluble Tc(IV), with a retarded first-order rate constant of 0.30 h-1. The presence of high concentrations of DOM only moderately inhibited the reduction effectiveness, and acidic pH was more favorable for Tc(VII) reduction. Column experiments showed that embedding a 0.8 cm pyrite layer of the material in a soil bed, simulating a permeable reactive barrier, was able to retard technetium transport 710 times more than a model sandy soil. The results demonstrated that the pyrite particles may serve as a long-lasting reactive material to remediate Tc-contaminated soil, groundwater and solid wastes.

Development of a Radiolabeled Amlodipine Analog for L-type Calcium Channel Imaging.

PURPOSE: The non-invasive imaging and quantification of L-type calcium channels (also known as dihydropyridine channels) in living tissues is of great interest in diagnosis of congestive heart failure, myocardial hypertrophy, irritable bowel syndrome etc. METHODS: Technetium-99m labeled amlodipine conjugate ([99mTc]-DTPA-AMLO) was prepared starting freshly eluted (<1 h) 99mTechnetium pertechnetate (86.5 MBq) and conjugated DTPAAMLO at pH 5 in 30 min at room temperature in high radiochemical purity (>99%, RTLC; specific activity: 55-60 GBq/mmol). The calcium channel blockade activity (CCBA) and apoptosis/necrosis assay of DTPA-amlodipine conjugate evaluations were performed for the conjugate. Log P, stability, bio-distribution and imaging studies were performed for the tracer followed by biodistribution studies as well as imaging. RESULTS: The conjugate demonstrated low toxicity on MCF-7 cells and CCBA (at µm level) compared to the amlodipine. The tracer was stable up to 4 h in final production and presence of human serum and log P (-0.49) was consistent with a water soluble complex. The tracer was excreted through kidneys and liver as expected for dihydropyridines; excluding excretory organs, calcium channel rich smooth muscle cells; including colon, intestine and lungs which demonstrated significant uptake. SPECT images supported the bio-distribution data up to 4 h. CONCLUSION: significant uptake of [99mTc]-DTPA-AMLO was obtained in calcium channel rich organs. The complex can be a candidate for further SPECT imaging for L-type calcium channels.

Bamboo (Acidosasa edulis) shoot shell biochar: Its potential isolation and mechanism to perrhenate as a chemical surrogate for pertechnetate.

In this work, a biochar was prepared from bamboo (Acidosasa edulis) shoot shell through slow pyrolysis (under 300-700 °C). Characterization with various tools showed that the biochar surface was highly hydrophobic and also had more basic functional groups. Batch sorption experiments showed that the biochar had strong sorption ability to perrhenate (a chemical surrogate for pertechnetate) with maximum sorption capacity of 46.46 mg/g, which was significantly higher than commercial coconut shell activated carbon and some adsorbents reported previously. Desorption experiments showed that more than 94% of total perrhenate adsorbed could be recovered using 0.1 mol/L KOH as a desorption medium. Pearson correlation analysis showed that the recovery of perrhenate by the biochars was mainly through surface adsorption mechanisms involving both high hydrophobicity and high basic sites of biochar surface.

99mTc-zolmitriptan: radiolabeling, molecular modeling, biodistribution and gamma scintigraphy as a hopeful radiopharmaceutical for lung nuclear imaging.

Lung imaging radiopharmaceuticals are helpful agents for measuring pulmonary blood flow and allow detection of pulmonary embolism and lung cancer. The goal of this study was to develop a novel potential radiopharmaceutical for lung imaging. Zolmitriptan (a selective serotonin receptor agonist) was successfully labeled with 99mTc via direct labeling method under reductive conditions studying different factors affecting the labeling efficiency. 99mTc-zolmitriptan was obtained with a maximum labeling yield of 92.5 ± 0.61 % and in vitro stability up to 24 h. Molecular modeling was done to predict the structure of 99mTc-zolmitriptan and ensure that radiolabeling did not affect binding ability of zolmitriptan to its receptor. Biodistribution studies showed that maximum lung uptake of 99mTc-zolmitriptan was 23.89 ± 1.2 % injected dose/g tissue at 15 min post-injection and retention in lungs remained high up to 1 h, whereas the clearance from mice appeared to proceed mainly via the renal pathway. Scintigraphic images confirmed the biodistribution results showing a high resolution lung image with low accumulation of radioactivity in other organs except kidneys and urinary bladder. 99mTc-zolmitriptan is not a blood product and so it is more safe than the currently available 99mTc-MAA, and its lung uptake is higher than that of the recently discovered 123I-IPMPD, 99mTc(CO)5I and 99mTc-DHPM. So, 99mTc-zolmitriptan could be used as a hopeful radiopharmaceutical for lung scintigraphic imaging.

Removal of TcO4(-) ions from solution: materials and future outlook.

Technetium mainly forms during artificial nuclear fission; it exists primarily as TcO4(-) in nuclear waste, and it is among the most hazardous radiation-derived contaminants because of its long half-life (t1/2 = 2.13 × 10(5) years) and environmental mobility. The high water solubility of TcO4(-) (11.3 mol L(-1) at 20 °C) and its ability to readily migrate within the upper layer of the Earth's crust make it particularly hazardous. Several types of materials, namely resins, molecular complexes, layered double hydroxides, and pure inorganic and metal-organic materials, have been shown to be capable of capturing TcO4(-) (or other oxoanions) from solution. In this review, we give a brief description about the types of materials that have been used to capture TcO4(-) and closely related oxyanions so far and discuss the possibility of using metal-organic frameworks (MOFs) as next-generation ion-exchange materials for the stated application. In particular, with the advent of ultra-stable MOF materials, in conjunction with their chemical tunability, MOFs can be applied to capture these oxyanions under real-life conditions.

Lingual Thyroid Ectopia: Diagnostic SPECT/CT Imaging and Radioactive Iodine Treatment.

BACKGROUND: Lingual thyroid is a rare abnormality of thyroid development that is usually treated conservatively with levothyroxine replacement. Rarely, it becomes large enough to cause obstructive symptoms in the oral cavity, requiring definitive treatment. PATIENT FINDINGS: This study reports on three patients with lingual thyroid treated with radioactive iodine-131 ((131)I) with successful radioablation of their ectopic thyroid tissues. Measurement of 24-hour radioactive iodine uptake within thyroidal tissues and hybrid single-photon emission computed tomography/computed tomography imaging using either iodine-123 or technetium-99m pertechnetate scans were performed in all patients demonstrating the location and size of lingual thyroid and absence of an orthotopic thyroid gland. SUMMARY: The aim of this study was to describe nonsurgical management of obstructive lingual thyroid tissue with (131)I therapy for lingual thyroid radioablation. Patients were prepared with a low-iodine diet and levothyroxine withdrawal prior to radioablation for optimizing (131)I uptake in ectopic thyroid tissues. Hybrid single-photon emission computed tomography/computed tomography measurement of anatomic size of lingual thyroid tissue and radioactive iodine uptake guided the selection of therapeutic doses, resulting in administration of 10.7, 17.5, and 15.4 mCi of (131)I, respectively. There were no post-therapy complications, and clinical follow-up demonstrated resolution of obstructive oropharyngeal symptoms. CONCLUSIONS: Ectopic lingual thyroid tissue is rarely associated with obstructive oropharyngeal symptoms due to progressive enlargement. Radioiodine therapy with (131)I is an effective treatment modality for ablation of ectopic thyroid tissue as an alternative to surgery.

(99)Tc(VII) Retardation, Reduction, and Redox Rate Scaling in Naturally Reduced Sediments.

An experimental and modeling study was conducted to investigate pertechnetate (Tc(VII)O4(-)) retardation, reduction, and rate scaling in three sediments from Ringold formation at U.S. Department of Energy's Hanford site, where (99)Tc is a major contaminant in groundwater. Tc(VII) was reduced in all the sediments in both batch reactors and diffusion columns, with a faster rate in a sediment containing a higher concentration of HCl-extractable Fe(II). Tc(VII) migration in the diffusion columns was reductively retarded with retardation degrees correlated with Tc(VII) reduction rates. The reduction rates were faster in the diffusion columns than those in the batch reactors, apparently influenced by the spatial distribution of redox-reactive minerals along transport paths that supplied Tc(VII). X-ray computed tomography and autoradiography were performed to identify the spatial locations of Tc(VII) reduction and transport paths in the sediments, and results generally confirmed the newly found behavior of reaction rate changes from batch to column. The results from this study implied that Tc(VII) migration can be reductively retarded at Hanford site with a retardation degree dependent on reactive Fe(II) content and its distribution in sediments. This study also demonstrated that an effective reaction rate may be faster in transport systems than that in well-mixed reactors.

Radioisotopic Purity of Sodium Pertechnetate 99mTc Produced with a Medium-Energy Cyclotron: Implications for Internal Radiation Dose, Image Quality, and Release Specifications.

UNLABELLED: Cyclotron production of 99mTc is a promising route to supply 99mTc radiopharmaceuticals. Higher 99mTc yields can be obtained with medium-energy cyclotrons in comparison to those dedicated to PET isotope production. To take advantage of this capability, evaluation of the radioisotopic purity of 99mTc produced at medium energy (20-24 MeV) and its impact on image quality and dosimetry was required. METHODS: Thick 100Mo (99.03% and 99.815%) targets were irradiated with incident energies of 20, 22, and 24 MeV for 2 or 6 h. The targets were processed to recover an effective thickness corresponding to approximately 5-MeV energy loss, and the resulting sodium pertechnetate 99mTc was assayed for chemical, radiochemical, and radionuclidic purity. Radioisotopic content in final formulation was quantified using γ-ray spectrometry. The internal radiation dose for 99mTc-pertechnetate was calculated on the basis of experimentally measured values and biokinetic data in humans. Planar and SPECT imaging were performed using thin capillary and water-filled Jaszczak phantoms. RESULTS: Extracted sodium pertechnetate 99mTc met all provisional quality standards. The formulated solution for injection had a pH of 5.0-5.5, contained greater than 98% of radioactivity in the form of pertechnetate ion, and was stable for at least 24 h after formulation. Radioisotopic purity of 99mTc produced with 99.03% enriched 100Mo was greater than 99.0% decay corrected to the end of bombardment (EOB). The radioisotopic purity of 99mTc produced with 99.815% enriched 100Mo was 99.98% or greater (decay corrected to the EOB). The estimated dose increase relative to 99mTc without any radionuclidic impurities was below 10% for sodium pertechnetate 99mTc produced from 99.03% 100Mo if injected up to 6 h after the EOB. For 99.815% 100Mo, the increase in effective dose was less than 2% at 6 h after the EOB and less than 4% at 15 h after the EOB when the target was irradiated at an incident energy of 24 MeV. Image spatial resolution and contrast with cyclotron-produced 99mTc were equivalent to those obtained with 99mTc eluted from a conventional generator. CONCLUSION: Clinical-grade sodium pertechnetate 99mTc was produced with a cyclotron at medium energies. Quality control procedures and release specifications were drafted as part of a clinical trial application that received approval from Health Canada. The results of this work are intended to contribute to establishing a regulatory framework for using cyclotron-produced 99mTc in routine clinical practice.

99m-Technetium binding site in bone marrow mononuclear cells.

INTRODUCTION: The increasing interest in 99m-technetium ((99m)Tc)-labeled stem cells encouraged us to study the (99m)Tc binding sites in stem cell compartments. METHODS: Bone marrow mononuclear cells were collected from femurs and tibia of rats. Cells were labeled with (99m)Tc by a direct method, in which reduced molecules react with (99m)Tc with the use of chelating agents, and lysed carefully in an ultrasonic apparatus. The organelles were separated by means of differential centrifugation. At the end of this procedure, supernatants and pellets were counted, and the percentages of radioactivity (in megabecquerels) bound to the different cellular fractions were determined. Percentages were calculated by dividing the radioactivity in each fraction by total radioactivity in the sample. The pellets were separated and characterized by their morphology on electron microscopy. RESULTS: The labeling procedure did not affect viability of bone marrow mononuclear cells. Radioactivity distributions in bone marrow mononuclear cell organelles, obtained in five independent experiments, were approximately 38.5 % in the nuclei-rich fraction, 5.3 % in the mitochondria-rich fraction, 2.2 % in microsomes, and 54 % in the cytosol. Our results showed that most of the radioactivity remained in the cytosol; therefore, this is an intracellular labeling procedure that has ribosomes unbound to membrane and soluble molecules as targets. However, approximately 39 % of the radioactivity remained bound to the nuclei-rich fraction. To confirm that cell disruption and organelle separation were efficient, transmission electron microscopy assays of all pellets were performed. CONCLUSIONS: Our results showed that most of the radioactivity was present in the cytosol fraction. More studies to elucidate the mechanisms involved in the cellular uptake of (99m)Tc in bone marrow cells are ongoing.

Microscopic validation of macroscopic in vivo images enabled by same-slide optical and nuclear fusion.

UNLABELLED: It is currently difficult to determine the molecular and cellular basis for radioscintigraphic signals obtained during macroscopic in vivo imaging. The field is in need of technology that helps bridge the macroscopic and microscopic regimes. To solve this problem, we developed a fiducial marker (FM) simultaneously compatible with 2-color near-infrared (NIR) fluorescence (700 and 800 nm), autoradiography, and conventional hematoxylin-eosin (HE) histology. METHODS: The FM was constructed from an optimized concentration of commercially available human serum albumin, 700- and 800-nm NIR fluorophores, (99m)Tc-pertechnetate, dimethyl sulfoxide, and glutaraldehyde. Lymphangioleiomyomatosis cells coexpressing the sodium iodide symporter and green fluorescent protein were labeled with 700-nm fluorophore and (99m)Tc-pertechnatate and then administered intratracheally into CD-1 mice. After in vivo SPECT imaging and ex vivo SPECT and NIR fluorescence imaging of the lungs, 30-µm frozen sections were prepared and processed for 800-nm NIR fluorophore costaining, autoradiography, and HE staining on the same slide using the FMs to coregister all datasets. RESULTS: Optimized FMs, composed of 100 µM unlabeled human serum albumin, 1 µM NIR fluorescent human serum albumin, 15% dimethyl sulfoxide, and 3% glutaraldehyde in phosphate-buffered saline (pH 7.4), were prepared within 15 min, displayed homogeneity and stability, and were visible by all imaging modalities, including HE staining. Using these FMs, tissue displaying high signal by SPECT could be dissected and analyzed on the same slide and at the microscopic level for 700-nm NIR fluorescence, 800-nm NIR fluorescence, autoradiography, and HE histopathologic staining. CONCLUSION: When multimodal FMs are combined with a new technique for simultaneous same-slide NIR fluorescence imaging, autoradiography, and HE staining, macroscopic in vivo images can now be studied unambiguously at the microscopic level.