C. Pascali

Radiation dose to technicians per nuclear medicine procedure: comparison between technetium-99m, gallium-67, and iodine-131 radiotracers and fluorine-18 fluorodeoxyglucose

Abstract.The aim of this study was to determine the non-extremity gamma dose received by a technician while performing an ordinary nuclear medicine procedure or a static (i.e. without blood sampling) fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) study. The dose per patient was measured by means of a commercial electronic pocket Geiger Mueller dosimeter, worn in the upper left pocket of the overalls. This was previously tested by exposure to known point sources of technetium-99m, gallium-67, iodine-131 and fluorine-18 in the air. A further test was performed with 99mTc, 131I and 18F sources inserted in a water phantom to simulate the condition of high scattering degradation of the primary radiation due to the patient’s tissues. Subsequently, the dose was measured by two technicians for a total of 314 clinical cases, covering the most common nuclear medicine procedures, including 44 static, two-level FDG PET studies with repositioning of the patient on the couch between the transmission and the emission scan and seven whole-body PET studies. The dose read by the dosimeter was corrected for environmental background and for detector efficiency measured with sources in the air. For a limited subset of cases, the time spent close to patients was also measured. Doses were then estimated by a crude non-absorbing point source approximation and by using experimental dose rates. A comparison between experimental and estimated doses, as well as with previously published data, completed the work. For most of the conventional procedures, the measured dose per procedure proved to be within the range 0.2–0.4 μSv, except for equilibrium angiocardioscintigraphy (1.0±0.5 μSv) and 99mTc-sestamibi single-photon emission tomography (1.7±1.0 μSv). Comparison with data published in the last 20 years shows that our values are generally lower. The current more favourable working conditions are a result of technological improvements (for instance two-head gamma cameras capable of whole-body studies), and safer shielding and distance from patients. Two-level PET gave 11.5±4.4 μSv and whole-body PET 5.9±1.2 μSv. In a subset of patients these values could be subdivided into the separate contributions from each phase of the procedure. They were: 0.11±0.04 μSv for daily quality assurance, 2.9±3.0 μSv for two transmission scans, 0.3±0.1 μSv for syringe preparation, 2.8±1.8 μSv for injection and escorting the patient to the waiting room, 1.7±1.5 μSv for a whole-body emission scan, 7.7±5.2 μSv for two emission scans, and 0.8±0.2 μSv for patient departure. The higher value from PET by comparison with conventional procedures is attributable to the higher specific gamma constant of 18F, as well as the longer time required for accurate positioning.

Comparison of three different methods for radiolabelling human activated T lymphocytes

One approach in the treatment of ovarian cancer MOv18/anti-CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian carcinomas and the CD3 T cell receptor. However, little is known about the in vivo biodistribution of injected activated lymphocytes, information that could be obtained by scintigraphic imaging of radiolabelled T cells in order to visualize the migratory pattern. We compared the efficiency, stability and toxicity of technetium-99m hexamethylpropylene amine oxime (HMPAO),indium-111 oxine and fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of111In-oxine and18F-FDG using 2.5×108 lymphocytes (68% and 64%, respectively) were more than twice that of99mTc-HMPAO (31%). Retention of the radionuclide in the cell was highest in the case of111In-oxine labelling (less than 25% of the initial cell-bound activity released after 240 min, as compared with 44% of the99mTc label in the same period and 45% of18F radionuclide released after 150 min). None of the three radiolabelling reagents induced any significant alteration in cell viability or immunophenotype. However, both111In-oxine and18F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian carcinoma cell line IGROV1, and all three radiolabelling reagents caused a significant reduction in the proliferative ability of labelled lymphocytes compared to controls, with cell death occurring after 8–9 days. Radiolabelling with the more stable111In-oxine reagent using a higher number of lymphocytes (1.4x109) but the same total activity (around 55.5 MBq) resulted in improved labelled T cell viability and proliferative ability, although the mean labelling efficiency decreased (35.8%). Together the data suggest that111In-oxine at low activity per cell is the most appropriate reagent for radiolabelling activated retargeted T lymphocytes useful for in vivo biodistribution studies.

The influence of blood glucose levels on [18F]fluorodeoxyglucose (FDG) uptake in cancer: A pet study in liver metastases from colorectal carcinomas

Aims and background To study the influence of blood glucose levels on the clinical reliability of positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) in the detection of liver metastases from colorectal carcinomas and in the analysis of tumor uptake of FDG. Methods After having given their informed consent, 8 patients with 20 liver metastases (mean size, 31.5 mm; range, 10–75 mm) detected by means of CT were submitted to a first FDG-PET examination under fasting conditions and, 2 days later, to a second FDG-PET examination performed after iv infusion of a glucose solution (4 mg/kg/min for 2 hrs). The results of the two studies were compared in each patient, considering both the localization of the metastases and the FDG uptake in the lesions. A non-kinetic method was used, calculating the Standardized Uptake Value (SUV). Results All 20 metastases were clearly visible on FDG-PET under fasting conditions. Moreover, in 2 patients FDG-PET detected a number of unknown liver metastases. The blood glucose levels after glucose infusion were significantly higher than the levels under fasting conditions, 158 ± 13.8 mg/100 ml (mean ± sd) and 92.4 ± 10.2, respectively (P « 0.001), and the quality of the FDG-PET images showed a marked deterioration. FDG-PET was unable to detect 6 of the 20 lesions and another 10 lesions were localized less clearly. Moreover, 80% of the unknown liver metastases were not detected after glucose loading. The SUVs of metastases decreased from 9.4 ± 5.7 (mean ± sd) under fasting conditions to 4.3 ± 8.3 after glucose loading (P « 0.001). Conclusions FDG-PET studies may be particularly unreliable under conditions of high levels of blood glucose. Therefore, patients entering FDG-PET studies should fast, and blood glucose concentration needs to be taken into account when evaluating FDG uptakes in follow-up studies.

A simple loop method for the automated preparation of (11C)raclopride from (11C)methyl triflate.

A simple automated preparation of [11C]raclopride by reaction of [11C]methyl triflate with demethylraclopride triflate is described. The conventional bubbling of [11C]methyl triflate into the precursor solution was compared with two alternative methods which used a commercially available C18 cartridge (on-column method) or an empty PTFE tube (loop method) as support for the precursor solution. The influence of several solvents was assessed for all three methods. The on-column method showed excellent trapping efficiencies of [11C]methyl triflate but gave the lowest radiochemical yields. The loop method proved to be a simplified alternative to the bubbling method, giving comparable radiochemical yields with less precursor and offering an easy way to transfer the reaction mixture into an HPLC column. By the simple-loop method [11C]raclopride could be prepared in over 40% radiochemical yields (decay-corrected and based on [11C]methyl triflate).

A new, convenient method for the preparation of 4-[18F]fluorobenzyl halides

A convenient method suitable for automated preparation of 4-[18F]fluorobenzyl halides from no-carrier-added [18F]fluoride has been developed. 4-[18F]Fluorobenzaldehyde, synthesized from [18F]fluoride by aromatic nucleophilic substitution on 4-trimethylammoniumbenzaldehyde triflate, was first retained on a C18 cartridge and there efficiently reduced to 4-[18F]fluorobenzyl alcohol simply by flowing an aqueous solution of NaBH4. The conversion of 4-[18F]fluorobenzyl alcohol to 4-[18F]fluorobenzyl halide was investigated using PBr3, PI3, P2I4, Ph3PBr2 and Ph3PI2 in CH2Cl2. 4-[18F]Fluorobenzyl halides were purified by passing through a disposable silica cartridge. The conversion rapidly proceeded in radiochemical yields of nearly 90% at 40 degrees C with P2I4 and almost quantitatively at room temperature with Ph3PBr2. With this last reagent 4-[18F]fluorobenzyl bromide was obtained in overall radiochemical yields of 50-60% within 30 min from EOB.

On-line [11C]methylation using [11C]methyl iodide for the automated preparation of 11C-radiopharmaceuticals

A novel method for the efficient preparation of 11C-radiopharmaceuticals by on-line [11C]methylation using [11C]methyl iodide has been developed and applied to a rapid, convenient automated system. [11C]Methyl iodide is first trapped in a short column, containing an adsorber and coated substrate, which is connected to an HPLC injector. DMF is then introduced. Alternatively the substrate is added with the DMF. A whole reaction mixture can be easily injected onto an HPLC column for purification by switching the injector valve immediately after the reaction. Thus, radiochemical yields in the preparation of 11C-labeled doxepin, benztropine, cyproheptadine and N-methylspiperone have been improved remarkably and the synthetic procedure simplified.

Improved preparation of l-[Methyl-11C]methionine by on-line [11C]methylation

Abstract On-line [ 11 C]methylation using [ 11 C]methyl iodide has been successfully applied to the preparation of l -[methyl- 11 C]-methionine ( 11 C-Met). [ 11 C]Methyl iodide is first trapped in a short column that contains Porapak Q and l -homocysteine thiolactone coated on inert support. The column is then charged with NaOH dissolved in a mixture of ethanol and water to cause the [ 11 C]methylation. The present method can provide practically pure 11 C-Met in radiochemical yield of over 98%. The whole procedure including the sterilization of final product has been completely automated for routine PET use.

Stability of L-[S-methyl-11C]methionine solutions

For clinical PET studies L-[S-methyl-11C]methionine ([11C]MET) solutions have been prepared in both high doses and specific activities (up to 48.1 GBq and 370 GBq/mmol, respectively) with high radiochemical purity (>99%). The stability of these preparations was investigated by HPLC to ensure the radiopharmaceutical efficacy during the usable shelf life. Under our routine conditions the observed radiochemical purity loss never exceeded 3.5% one hour after EOS. The decomposition rate was affected by total activity and chemical composition of the solutions.

A System for the automatic monitoring and safe disposal of short-lived radioactive gaseous compounds from hot-cells in a PET facility

Abstract A novel automated system for the detection and disposal of radioactive gases emitted within the walls of a hot-cell is described. The system has been designed and installed at the Nuclear Medicine Divisions FET Unit of the National Cancer Institute of Milan (Italy). Basically, a radiation detector monitors the air exhausted from the hot-cell, which is normally released through the hospital main chimmey. Beyond a selected threshold of radioactivity concentration, the air flow is automatically conveyed to a buffer tank. A set of measures to ensure radiation safety to the chemist is also reported.

Minimization of the amount of Kryptofix 222 - KHCO3 for applications to microscale 18F-radiolabeling

Conversion of aqueous [18F]fluoride to reactive [18F]fluoride is an important first step in the radiosynthesis of 18F-labeled compounds by nucleophilic substitution. A versatile method for the rapid preparation of reactive [18F]fluoride by the combined use of an Oasis MAX cartridge and a methanolic solution of the Kryptofix 222-KHCO3 complex (K.222/KHCO3) was developed. The latter amount was optimized with the aim to keep it as low as possible while achieving recovery yields of [18F]fluoride comparable to those attained with the commonly used QMA cartridge. Thus, a 97% recovery yield was obtained with just 2µmol of K.222/KHCO3 methanolic solution (10mM, 200µL) within 7min. This result allowed in turn to optimize the microscale radiosynthesis of [18F]FDG. Moreover, the method was successfully applied to the 100µL-scale 18F-substitution reactions of several precursors.