Validation of the HPLC Analytical Method for the Determination of Chemical and Radiochemical Purity of Ga-68-DOTATATE.

Purpose of the Study: Ga-68-DOTA-peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumors imaging using positron emission tomography (PET). A new selective and sensitive high-pressure liquid chromatography (HPLC) method was developed for determining chemical and radiochemical purity of Ga-68-DOTATATE (PET) tracer. The identification of peaks was achieved on a symmetry C18 column 3 µm 120Å (3.0 mm × 150 mm spherical particles) using (A) water + 0.1% trifluoroacetic acid (TFA) and (B) acetonitrile + 0.1% TFA, as the mobile phases at a flow rate of 0.600 mL/min and monitored at 220 nm. The run time was 16 min. Materials and Methods: The method was validated to fulfill International Conference on Harmonization requirements and EDQM guidelines, and it included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision. Results: The calibration curve was linear over the concentration range from 0.5 to 3 µg/ml, with a correlation coefficient (r2) equal to 0.999, average coefficient of variation (CV%) 2%, and average bias% did not deviate more than 5% for all concentrations. The LOD and LOQ for DOTATATE were 0.5 and 0.1 µg/mL, respectively. The method was considered precise, obtaining coefficients of variation between 0.22% and 0.52% for intraday and 0.20% and 0.61% for interday precision. Accuracy of method was confirmed with average bias% that did not deviate more than 5% for all concentrations. Conclusion: All results were acceptable and this confirmed that the method is suitable for its intended use in routine quality control of Ga-68-DOTATATE to guarantee the high quality of the finished product before release.

Performance and long-term consistency of five Galliform 68Ge/68Ga generators used for clinical Ga-68 preparations over a 4 year period.

BACKGROUND: Gallium-68 is a positron emitter for PET applications that can be produced without cyclotron by a germanium (Ge-68) chloride/gallium (Ga-68) chloride generator. Short half-life (67.71 min) of Ga-68, matching pharmacokinetic properties of small biomolecules, facilitates isotope utilization in compounding radiopharmaceuticals for PET imaging. The increasing cost of good manufacturing practice-compliant generators has strengthened the need for radionuclide efficient use by planning specific radiopharmaceutical sessions during the week, careful maintenance of the generator and achievement of high labeling yield and radiochemical purity (RCP) of the radiolabeled molecules. METHODS: The aim of this study was to evaluate the annual performance of five consecutive 68Ge/68Ga generators used for small-scale preparations of 68Ga-radiopharmaceuticals. To assess the long-term efficiency of isotope production we measured the weekly elution yield. To assess process efficiency we measured elution yield, labeling yield and RCP of four radiopharmaceutical preparations (68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68Ga-PENTIXAFOR and 68Ga-DOTATATE). RESULTS: The annual mean elution yield of the generators was 74.7%, higher than that indicated by the manufacturer, and it never went below 65%. The Ge-68 level in the final products was under the detection limits in all the produced batches (mean value 0.0000048%). The RCP of radiopharmaceuticals determined by high-performance liquid chromatography was 98 ± 0.22%. The mean yield of radiolabelling was 64.68, 68.71, 57 and 63.68% for 68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68GaPENTIXAFOR and 68Ga-DOTATATE. CONCLUSION: The ability to prepare in the hospital radiopharmacy high-purity and pharmaceutically acceptable 68Ga-radiolabeled probes on a routine basis facilitates patient access to precision imaging for clinical and research aims.

Novel approach for quality assessment and improving diagnostic accuracy in cell-based infection imaging using 99mTc-HMPAO labeled leukocytes.

BACKGROUND AND AIM: Labeled leukocytes with 99mTc-HMPAO are routinely used for infection imaging. Although cell labeling with 99mTc-HMPAO represents an imaging probe to detect infection sites, the diagnostic efficiency of the probe is largely influenced by cell manipulation, multidisciplinary interventions (i.e., biologist, technicians) and available technology (i.e., SPECT, SPECT/CT). The aim of the study was to assess in vitro and in vivo accuracy of a comprehensive approach for quality assessment (QA) of all steps of the procedure. METHODS: Radiochemical purity (RCP), pH, labeling efficiency (LE) were measured in 320 procedures. White Cell Viability Factor (WVF) was determined in consecutive blood samples. Images (490 studies) were scored using a 5-point scale. Training program was evaluated using a Learning Questionnaire and a score system. RESULTS: Pre/post-labelling WVF was 0.99% (max value 1%) in all blood samples. LE (mean value 72%) and RCP (>80% until 55 minutes) yielded considerably high values. The vast majority of images were scored as diagnostic by three independent observer (90% with score ≥4). CONCLUSIONS: This method appears highly reproducible and easy to use in clinical routine for leukocyte labeling, especially when standardized training and total QA system are implemented.

Radiation dose reduction in myocardial perfusion imaging single-photon emission computed tomography/computed tomography using a dose-tracking software.

OBJECTIVE: We describe our experience with a dose-tracking software (Radimetrics) that was used to optimize, from a dosimetric point of view, the single-photon emission computed tomography/computed tomography protocols used in myocardial perfusion imaging. PATIENTS AND METHODS: We extracted and assessed the major dosimetric indices as the administered activity, the computed tomography dose index, the dose length product and the size-specific dose estimates for a large sample of patients before and after an optimization process. We also evaluated both the effective and the equivalent dose to organs for all the procedures. RESULTS: We achieved a reduction in administered activity by 17.8 and 4.5% for 2- and 1-day protocols, respectively; moreover size-specific dose estimates related to a single computed tomography acquisition was reduced by 50%. The organs that received the highest equivalent dose were the heart and the breast, and with the new protocols, these values were almost halved.The average single-photon emission computed tomography/computed tomography myocardial perfusion imaging effective dose decreased from 21.9±2.5 to 15.6±1.4 mSv for the 2-day protocol and from 17.8±1.7 to 13.6±1.5 mSv for the 1-day protocol. This meant that with a simple but targeted action on acquisition protocols, it was possible to achieve considerable dosimetric reduction.The adoption of a dose-tracking software represented an easy approach to optimization. Furthermore, we could easily calculate the main dosimetric indices and check their trends day by day to perform the necessary corrective actions in real timeVideo abstract: http://links.lww.com/NMC/A135.

Development and Validation of a High-Pressure Liquid Chromatography Method for the Determination of Chemical Purity and Radiochemical Purity of a [68Ga]-Labeled Glu-Urea-Lys(Ahx)-HBED-CC (Positron Emission Tomography) Tracer.

Background: Prostate-specific membrane antigen (PSMA) has gained high attention as a useful biomarker in the imaging evaluation of prostate cancer with positron emission tomography (PET) during recent years. [68Ga]-labeled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]-PSMA-HBED-CC) is a novel PSMA inhibitor radiotracer which has demonstrated its suitability in detecting prostate cancer. Preparation conditions may influence the quality and in vivo behavior of this tracer, and no standard procedure for the quality control (QC) is available. The aim of this study was to develop a new rapid and simple high-pressure liquid chromatography method of analysis for the routine QCs of [68Ga]-PSMA-HBED-CC to guarantee the high quality of the radiopharmaceutical product before release. Methods: A stepwise approach was used based on the quality by design concept of the International Conference of Harmonisation Q2 (R1) and Q8 (Pharmaceutical Development) guidelines in accordance with the regulations and requirements of European Association of Nuclear Medicine, Society of Nuclear Medicine, International Atomic Energy Agency, World Health Organization, and Italian Association of Nuclear Medicine and Molecular Imaging. The developed analytical test method was validated because a specific monograph in the pharmacopoeia is not available for [68Ga]-PSMA-HBED-CC. Results: The purity and quality of the radiopharmaceutical obtained according to the proposed method resulted high enough to safely administrate it to patients. An excellent linearity was found between 0.8 and 5 µg/mL, with a detection limit of 0.2 µg/mL. Assay imprecision (% CV) was <2%. Conclusions: The developed method to assess the radiochemical and chemical purity of [68Ga]-PSMA-HBED-CC is rapid, accurate, and reproducible, allowing routinely the use of this PET tracer as a diagnostic tool for imaging prostate cancer and also assuring patient safety.

Physical characterization of a new CT iterative reconstruction method operating in sinogram space.

Recently a new iterative reconstruction algorithm named Iterative Reconstruction (SAFIRE) has been released by Siemens. This algorithm works in the raw data domain with noise reduction as main purpose, providing five different strengths. In this study, the effect of SAFIRE on image quality has been investigated using selected phantoms and a comparison with standard filtered back projection (FBP) has been carried out. The following quantitative parameters have been evaluated: image noise, impact of different reconstruction kernels on noise reduction, noise power spectrum (NPS), contrast-to-noise ratio (CNR), spatial resolution, and linearity and accuracy of CT numbers. The influence of strengths on image quality parameters has also been examined. Results show that image noise reduction is independent of reconstruction kernel and strongly related to the strength of SAFIRE applied. The peak of NPS curve for SAFIRE reconstructions is shifted towards low frequencies; this effect is more marked at higher levels of strength. Contrast-to-noise ratio is always improved in SAFIRE reconstruction and increases with higher strength. At different dose levels SAFIRE preserves CT number accuracy, linearity, and spatial resolution, both in transversal and coronal planes. These results confirm that SAFIRE allows for image noise reduction with preserved image quality. First clinical data to validate this phantom analysis and confirm that commercially available iterative algorithms can play an effective role in dose containment.