Published methods for radiolabelling of 1,4,7-triazacyclononane-1,4,7-triacetic acid ubiquicidin (NOTA-UBI) 29-41 to date describe manual or kit-based procedures. The purpose of this study was to develop an automated synthesis method for the synthesis of [ 68 Ga]Ga-NOTA-UBI. NOTA-UBI was successfully labelled with gallium-68 using the three different automated procedures. The use of radical scavengers to improve radiochemical purity is also discussed. The automated procedures showed a high degree of robustness and repeatability. The validated automated synthesis protocols using a Scintomics GRP Module will contribute to provide GMP-compliant [ 68 Ga]Ga-NOTA-UBI for clinical infection imaging.

The labeling of peptides with gallium-68 is often initially performed by manual labeling, but with high clinical demand, other alternatives are needed. Coldkits or automated synthesis are viable options for standardized methods and deemed pharmaceutically more acceptable. This study compares these [ 68 Ga] Ga-PSMA-11 production methods. Data from 40 kit-based and 40 automated syntheses of [ 68 Ga]Ga-PSMA-11 were analyzed. Pre-set criteria were evaluated including radiochemical purity, radionuclidic purity, chemical purity, physiological acceptability and sterility. The operator time and radiation dose received were measured. The robustness and repeatability of each method were assessed and a comparison of the running costs of each method is also provided. For both the methods all the analyzed products met the release criteria. No differences were found in radiochemical purity, radiochemical identity, radionuclidic purity, and sterility. However, radiochemical yield and apparent molar activity showed significant differences. For both methods, whole body radiation exposure to operators was lower than with manual labeling (25-40 μSv). The exposure during kit-based labeling (14.5 ± μSv) was seven times higher than that of automated synthesis (2.05 ± 0.99 μSv). The automated synthesis was the more expensive method. Both methods are sound alternatives to manual synthesis and offer higher quality, better radiation protection and a more reliable manufacturing of radiopharmaceuticals.

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The single vial kit formulations met the quality release specifications for human administration and appear to be highly advantageous over using peptide stock solutions in terms of stability and user-friendliness.

Purpose. Striatal single photon emission computed tomography (SPECT) imaging of the dopaminergic system is becoming increasingly used for clinical and research studies. The question about the value of nonuniform attenuation correction has become more relevant with the increasing availability of hybrid SPECT-CT scanners. In this study, the value of nonuniform attenuation correction and correction for collimator blurring were determined using both phantom data and patient data. Methods. SPECT imaging was performed using 7 anthropomorphic phantom measurements, and 14 patient studies using [I-123]-FP-CIT (DATSCAN). SPECT reconstruction was performed using uniform and nonuniform attenuation correction and collimator blurring corrections. Recovery values (phantom data) or average-specific uptake ratios (patient data) for the different reconstructions were compared at similar noise levels. Results. For the phantom data, improved recovery was found with nonuniform attenuation correction and collimator blurring corrections, with further improvement when performed together. However, for patient data the highest average specific uptake ratio was obtained using collimator blurring correction without nonuniform attenuation correction, probably due to subtle SPECT-CT misregistration. Conclusions. This study suggests that an optimal brain SPECT reconstruction (in terms of the lowest bias) in patients would include a correction for collimator blurring and uniform attenuation correction.

HEPES (4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) is a buffer that is used in the radiolabelling of gallium-68 compounds. The beneficial effects of HEPES on molar activity in bioconjugates have been well described. Current strict regulations on the HEPES content in radiopharmaceuticals limit its use when intended for parenteral administration.This short communication summarizes data from the literature on the toxicity of HEPES in dogs after intravenous infusion and the subsequent use in humans. We also highlight the use of HEPES in an FDA labelled intravenous drug formulation. Regulatory institutions may consider this data to review current strict limits.

The amount of radioactivity excreted in breast milk following administration of 11 different radiopharmaceuticals, including technetium-99m labelled microspheres, pyrophosphate, diisopropyl-iminodiacetic acid (DISIDA) and sestamibi, has been measured. This report summarises the data collected from 60 patients. An effective decay constant for the series of samples from each patient was calculated from exponential curves fitted by least squares to the data. It is difficult to compare values from individual patients, since times of expression, volumes of milk and the activity administered are not uniform. In order to formulate reliable guidelines, we therefore calculated the total activity theoretically excreted in milk until complete decay of the radionuclide, which is usually higher than that actually measured over the actual period of collection. Of the various 99mTc compounds, pertechnetate clearly reaches the highest concentrations in breast milk. The wide variability of data from different patients who received the same radiopharmaceutical despite identical methods of sample collection and data processing confirms the impression gained from literature that transfer of radionuclides into milk varies greatly between individuals. Although we have calculated average values for each compound, very large standard deviations were obtained, and we believe that for radiation protection purposes, a "worst case" approach is the most appropriate. With new data available and the revision of ICRP recommendations, the guidelines applicable when radiopharmaceuticals are administered to breast-feeding mothers are reviewed. The effective dose resulting from close contact between patient and infant was included in these calculations. Breast feeding need not be interrupted after administration of 99mTc-DISIDA, -sulphur colloid, -gluconate and -methoxyisobutylisonitrile (MIBI). However, after administration of 99mTc-MIBI, close contact should be restricted. 99mTc-pyrophosphate and -microspheres require interruption periods of several hours. High activities of 99mTc-pertechnetate may require interruption longer than 2 days. For pertechnetate and 99mTc-labelled red blood cells, interruption of breast feeding with measurement of activity in expressed milk samples is recommended. Breast feeding is contra-indicated after administration of 67Ga and 131I. General guidelines regarding breast feeding after administration of radiopharmaceuticals are summarised.

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