Compatibility of [99mTc]Tc-EDDA/HYNIC-TOC and [68Ga] Ga-DOTA-TOC in a syringe for intravenous administration.

OBJECTIVE: Drug quality in medical devices is not evaluated during the marketing authorization of radiopharmaceuticals. Therefore, the extemporaneous change of packaging made for preparation of patient unit doses in a syringe is the responsibility of radiopharmacists. The present study aimed to determine the impact of packaging and storage in a polypropylene syringe on the quality of hydrophilic drugs [Tc]Tc-EDDA/HYNIC-TOC (Tektrotyd) and [Ga]Ga-DOTA-TOC (Somakit-TOC). METHODS: Appearance, pH, radiochemical purity, sterility, and endotoxin tests were performed according the current European Pharmacopoeia. Subvisible and visible particles tests of the European Pharmacopoeia were adapted due to limited preparation volume (<25 ml). Sorption tests were performed according to the literature. RESULTS: After 2 h storage in a syringe, drug sorption of Tektrotyd and Somakit-TOC was of less than 2.5% and similar to other Tc-radiopharmaceuticals (range: from 1.1 ± 0.5% to 4.2 ± 0.6%). For Tektrotyd, this sorption phenomenon was positively influenced by the drug concentration and a short contact with the medical device (4.8 ± 0.2% up to 5 s vs. 2.3 ± 0.2%, n = 4; P < 0.001). For Somakit-TOC, the duration of contact with syringe had no impact (1.6 ± 0.2% up to 5 s vs. 1.7 ± 0.6%; P = 1.000). No drug radiolysis or alteration of microbiological aspects were observed. No impurity from a 3-piece-syringe was observed according to drug aspect, pH, and subvisible and visible particles, which remained within specification of the current European Pharmacopoeia. CONCLUSION: This study found that drug sorption to packaging was compatible with clinical use and absence of drug alteration of Tektrotyd and Somakit-TOC after repackaging in a syringe in polypropylene and prolonged storage during 2 h.

Feasibility and Evaluation of Automated Methods for Radiolabeling of Radiopharmaceutical Kits with Gallium-68.

OBJECTIVES: Recent gallium-68 labeled peptides are of increasing interest in PET imaging in nuclear medicine. Somakit TOC® is a radiopharmaceutical kit registered in the European Union for the preparation of [68Ga]Ga-DOTA-TOC used for the diagnosis of neuroendocrine tumors. Development of a labeling process using a synthesizer is particularly interesting for the quality and reproducibility of the final product although only manual processes are described in the Summary of Product (SmPC) of the registered product. The aim of the present study was therefore to evaluate the feasibility and value of using an automated synthesizer for the preparation of [68Ga]Ga-DOTA-TOC according to the SmPC of the Somakit TOC®. METHODS: Three methods of preparation were compared; each followed the SmPC of the Somakit TOC®. Over time, overheads, and overexposure were evaluated for each method. RESULTS: Mean±SD preparation time was 26.2±0.3 minutes for the manual method, 28±0.5 minutes for the semi-automated, and 40.3±0.2 minutes for the automated method. Overcost of the semi-automated method is 0.25€ per preparation for consumables and from 0.58€ to 0.92€ for personnel costs according to the operator (respectively, technician or pharmacist). For the automated method, overcost is 70€ for consumables and from 4.06€ to 6.44€ for personnel. For the manual method, extremity exposure was 0.425mSv for the right finger, and 0.350mSv for the left finger; for both the semi-automated and automated method extremity exposure were below the limit of quantification. CONCLUSION: The present study reports for the first time both the feasibility of using a [68Ga]- radiopharmaceutical kit with a synthesizer and the limits for the development of a fully automated process.

Radiolabeling of annexin A5 with (99m)Tc: comparison of HYNIC-Tc vs. iminothiolane-Tc-tricarbonyl conjugates.

In the perspective of expanding the use of annexin A5 (anx A5) as radioactive tracer of cell death in vivo, we recently described its radiolabeling with (99m)Tc-tricarbonyl [(99m)Tc(H(2)O)(3)(CO)(3)](+) via the mercaptobutyrimidyl group (anx A5-SH). The aim of the present article was to compare this new method with the HYNIC strategy (anx A5-HYNIC), recognized at present as the reference for the radiolabeling of proteins with (99m)Tc. Similar radiolabeling yields and better chemical stability were obtained with the [anx A5-SH-(99m)Tc-tricarbonyl] complex. Since the [anx A5-HYNIC-(99m)Tc(tricine)(2)] conjugate shows isomeric forms which can affect the biological properties whereas [anx A5-SH-(99m)Tc-tricarbonyl] is less or not prone to such drawback, the latter seems superior to the former. Furthermore, (anx A5-SH) is readily obtained via commercial sources of Traut's reagent whereas (anx A5-HYNIC) is not. The results provide encouraging evidence in the development of anx A5-labeled reagent for apoptose imaging.

Fractionated elution of 99Mo/99mTc generators using calibrated vials.

Fractionated elution consists in collecting the fractions of an eluate with the highest radioactive concentration. It may be useful to meet the requirements of a subset of clinical radiopharmacy procedures. This study aims to describe and evaluate straightforward procedures allowing to readily perform fractionated elution on dry and wet columns Mo/Tc generators by using calibrated vials. The main objectives of this study consisted in determining the relationship between eluate volume and elution yield using different vials calibration and assessing repeatability of the procedure. Elution vials were calibrated to obtain different eluate volumes by addition of air for wet column generator (WCG) and subtraction of saline for dry column generator (DCG) (n≥5 for each calibration). The relationship between the eluate volume and the elution yield was determined by a regression model for both DCG and WCG. Then repeatability evaluation was performed using 3-ml vial calibration. Relationships between the eluate volume (V) and the elution yield (Y) for DCG and WCG were Y=57.551 ln(V)+10.526 and Y=50.256 ln(V)+17.597, respectively. For repeatability assessment (n=30 for DCG and n=31 for WCG), the median volume and the interquartile range for DCG and WCG were 2.98 ml (2.92-3.01) and 3.28 ml (2.71-3.40), respectively, and median (interquartile range) eluate yields were 84.73% (81.30-86.33) and 81.78% (78.91-85.20), respectively. The volume was significantly higher for WCG than DCG (P=0.036) and also significantly more variable (P<0.001). The elution yield was significantly lower for WCG than DCG (P=0.025), but no difference in variability between the two generators was found (P=0.874). Easy-to-handle fractionated elution methods are compatible with both DCG and WCG. Fractionation using calibrated vials exhibits a better reproducibility with DCG than WCG generators and represents the only proposed method so far to master fractionated elution with DCG.

Improving radiopharmaceutical supply chain safety by implementing bar code technology.

The aim of this study was to describe and evaluate an approach for improving radiopharmaceutical supply chain safety by implementing bar code technology. We first evaluated the current situation of our radiopharmaceutical supply chain and, by means of the ALARM protocol, analysed two dispensing errors that occurred in our department. Thereafter, we implemented a bar code system to secure selected key stages of the radiopharmaceutical supply chain. Finally, we evaluated the cost of this implementation, from overtime, to overheads, to additional radiation exposure to workers. An analysis of the events that occurred revealed a lack of identification of prepared or dispensed drugs. Moreover, the evaluation of the current radiopharmaceutical supply chain showed that the dispensation and injection steps needed to be further secured. The bar code system was used to reinforce product identification at three selected key stages: at usable stock entry; at preparation-dispensation; and during administration, allowing to check conformity between the labelling of the delivered product (identity and activity) and the prescription. The extra time needed for all these steps had no impact on the number and successful conduct of examinations. The investment cost was reduced (2600 euros for new material and 30 euros a year for additional supplies) because of pre-existing computing equipment. With regard to the radiation exposure to workers there was an insignificant overexposure for hands with this new organization because of the labelling and scanning processes of radiolabelled preparation vials. Implementation of bar code technology is now an essential part of a global securing approach towards optimum patient management.

Comparison of three radiochemical purity control methods of (99m)Tc-macroaggregated albumin.

(99m)Tc-macroaggregated albumin is widely used to diagnose pulmonary embolism. To control the radiochemical purity of this radiopharmaceutical, three rapid control methods using filter, thin layer chromatography or centrifugation, are described in the academic literature. In this paper, the interactions between impurities and (99m)Tc-macroaggregated albumin were presented. For each control method, the influence of these interactions on the determination of the radiochemical purity of labeled macroaggregated albumin was evaluated. Then, a comparison of radiochemical purity obtained by these three methods was performed in normal condition and with different addition of pertechnetate. Finally, a correlation between these three methods was investigated. The results show a specificity difference between these three control methods. However in practice, this difference has no impact on the evaluation of the radiochemical purity of (99m)Tc-macroaggregated albumin by these three methods. In additions, methods are still correlated with pertechnetate additions in (99m)Tc-macroaggregated albumin suspension. Thus, this study demonstrates that these three control methods are exchangeable in radiopharmacy.