Development of a remote purification apparatus with disposable evaporator for the routine production of high-quality 64Cu for clinical use.

We developed a new apparatus for the routine production of 64Cu in clinical use. The apparatus has many disposable parts that stabilize the product quality (such that there is a low deviation of the concentrations of impurity metals in the product) and reduce the work load of preparation for routine production. We also developed a new evaporator using near-infrared heaters for disposable use. We conducted a production test using the new apparatus and evaluated product quality. The product yield was 6.3 ±â€¯0.32 GBq (end of bombardment) (N = 4), the product quality in terms of the concentrations of impurity metals (Cu2+, Ni2+, Fe3+, Zn2+, Mn2+) was as good as that usually achieved, likely on the order of parts per billion, and the preparation time was reduced from 2 days to 1 day.

Comparative Evaluation of Anti-HER2 Affibody Molecules Labeled with 64Cu Using NOTA and NODAGA.

Imaging using affibody molecules enables discrimination between breast cancer metastases with high and low expression of HER2, making appropriate therapy selection possible. This study aimed to evaluate if the longer half-life of 64Cu (T1/2 = 12.7 h) would make 64Cu a superior nuclide compared to 68Ga for PET imaging of HER2 expression using affibody molecules. The synthetic ZHER2:S1 affibody molecule was conjugated with the chelators NOTA or NODAGA and labeled with 64Cu. The tumor-targeting properties of 64Cu-NOTA-ZHER2:S1 and 64Cu-NODAGA-ZHER2:S1 were evaluated and compared with the targeting properties of 68Ga-NODAGA-ZHER2:S1 in mice. Both 64Cu-NOTA-ZHER2:S1 and 64Cu-NODAGA-ZHER2:S1 demonstrated specific targeting of HER2-expressing xenografts. At 2 h after injection of 64Cu-NOTA-ZHER2:S1, 64Cu-NODAGA-ZHER2:S1, and 68Ga-NODAGA-ZHER2:S1, tumor uptakes did not differ significantly. Renal uptake of 64Cu-labeled conjugates was dramatically reduced at 6 and 24 h after injection. Notably, radioactivity uptake concomitantly increased in blood, lung, liver, spleen, and intestines, which resulted in decreased tumor-to-organ ratios compared to 2 h postinjection. Organ uptake was lower for 64Cu-NODAGA-ZHER2:S1. The most probable explanation for this biodistribution pattern was the release and redistribution of renal radiometabolites. In conclusion, monoamide derivatives of NOTA and NODAGA may be suboptimal chelators for radiocopper labeling of anti-HER2 affibody molecules and, possibly, other scaffold proteins with high renal uptake.

Standardization of 64Cu and 68Ga by the 4π(PC)ß-γ coincidence method and calibration of the ionization chamber.

The paper treats the application of the 4π(PC)ß-γ coincidence method for the standardization of the radionuclides (64)Cu and (68)Ga. The general coincidence equations are written. Two types of extrapolation were described and used in measurement: the positron-annihilation coincidence, and the counting of all emitted radiations; both methods are compared with respect to results, advantages and drawbacks. The impurities' content correction was applied. The standardized solutions were used to calibrate the ionization chamber CENTRONIC IG12/20A and to determine the gamma-rays emission intensities.

Activity standardization and decay data of 64Cu.

The activity of a solution of (64)Cu was measured by 4pibeta(PC)-gamma coincidence counting and liquid scintillation counting using the CIEMAT/NIST method. In addition, 4pi ionization chambers were used to establish and preserve calibration factors for secondary standardizations and for a determination of the half-life, for which a value of 12.704(5)h was measured. The photon emission probabilities were determined using gamma-ray spectrometry, finding values of p(511 keV)=0.3512(22) and p(1346 keV)=0.00474(5). The results were checked for consistency, and an ampoule was submitted to the BIPM to have the activity result entered into the database of the International Reference System (SIR), yielding the first entry for this radionuclide.

The standardization of 62Cu and experimental determinations of dose calibrator settings for generator-produced 62CuPTSM.

The Positron Emission Tomography agent 62Cu Pyruvaldehyde Bis(N4-methyl)thiosemicarbazone (PTSM) has been standardized by the National Institute of Standards and Technology (NIST) using 4 pi beta liquid scintillation counting with 3H-standard efficiency tracing. Using a measurement model developed at NIST for the determination of experimental dose calibrator dial settings for short-lived radionuclides, the correct dial settings for 62CuPTSM in a clinically useful geometry (a 35 ml plastic syringe containing 33 ml of solution) as well as the standard NIST 5 ml glass ampoule have been elucidated. This measurement model is fully described, as is the treatment of associated uncertainties. The correct instrument settings for the NIST Capintec CRC-12 re-entrant ionization chamber ('dose calibrator') were found to be '499 +/- 6' and '489 +/- 8', respectively, for the syringe and ampoule geometries. The stated uncertainties are expanded (k = 2) uncertainties. The expanded uncertainties in the measured activity arising from these new dial settings are +/- 0.8% and +/- 1.4%, respectively, for the syringe and ampoule. The measured activities using these settings are lower than those obtained from the manufacture's recommended setting of '448' by 9.7% for the syringe and 7.7% for the ampoule, and underscore the need for experimental verification of the dose calibrator settings for each radionuclide and each geometry used in the clinic.

Accurate measurement of copper-67 in the presence of copper-64 contaminant using a dose calibrator.

UNLABELLED: The use of 67Cu-labeled antibodies for the treatment of cancer has advanced to the clinical trial phase. Quantitation of 67Cu radiopharmaceuticals is complicated by the presence of the radioimpurity of 64Cu in 67Cu supplies. Here we report a method to assay 67Cu and 64Cu in a mixed sample with a commonly available instrument, the ionization chamber dose calibrator. METHODS: The activities of 67Cu and 64Cu in a mixed sample can be calculated from a single-dose calibrator measurement. The calculation requires (1) instrument-specific response coefficients D67 and D64, generated by gauging the instrument for the efficiency of measurement of 67Cu and 64Cu, and (2) a value for the ratio of 67Cu to 64Cu in the sample, routinely provided by major suppliers of 67Cu. D67 and D64 were empirically determined by measuring samples containing known amounts of 67Cu and 64Cu. The samples were also assayed by gamma ray spectroscopy to verify the isotope ratios given by the suppliers. RESULTS: This method generated accurate response coefficients. At the recommended dose calibrator setting for the measurement of 67Cu, at which D67 = 1.0, the measurement for D67 with this method was 1.02 (+/- 0.04). Isotope ratios provided by the radionuclide suppliers were corroborated by gamma ray spectroscopy. CONCLUSION: A method is presented by which 67Cu and 64Cu in a mixed sample can be assayed using a dose calibrator. Although the derived numeric constants are only correct for a specific dose calibrator and setting, the method can be adapted for use with any dose calibrator.