Absolute counting of 188Re radiopharmaceuticals.

The Institute of Nuclear Energy Research (INER) has provided 188Re radiopharmaceuticals for hospitals in Taiwan. To enhance the accuracy of commercial radionuclide calibrators used by radiopharmacies and hospitals, and to ensure that patients receive proper doses of these radiopharmaceuticals, it is very important to standardize this nuclide. The 4pibeta-gamma coincidence counting method was used to standardize the mass activities of 188Re in this study. At the same time, three well type ionization chambers, Centronic IG11-N20, Centronic IG11-A20, and ISOCAL-IV, were calibrated by the standardized solutions of the nuclide. In this research, the calibration figures of ISOCAL-IV for the nuclide were consistent with the results of National Physical Laboratory (NPL, UK). The outcome implied that the results of coincidence counting did mutually agree. On the other hand, the radionuclide calibrator in the radiopharmacy was producing measurement errors of about 20% when using the manufacturers recommended calibration setting: an accurate correction factor has now been determined in this study.

Precise measurement of the activity of 186Re, 188Re radiopharmaceuticals.

The paper presents the results obtained in the assurance of traceability along the whole chain: production, distribution, use in hospitals, for the activity measurement of radiopharmaceuticals containing 186Re, 188Re and 186Re + 188Re mixtures. Standardization of the solutions, 4piPC-beta-efficiency relations and responses of a Centronic IG 12/20A ionization chamber and other radioisotope calibrators are presented. Gamma-ray and bremsstrahlung radiation contributions in the total response were evaluated. Some of the relevant results were compared with literature data.

Labeling and quality control of 188Re-lanreotide.

Lanreotide was labelled with 188Re obtained from 188W/188Re generator, using stannous ion as reducing agent, ascorbic acid as stabilizers and hydroxy ethylidene bisphosphonate (HEDP) as intermediary ligand at different molar ratios, pH and incubation times. Best yields (>95%) were obtained using molar ratios SnF2/lanreotide, ascorbic/lanreotide and HEDP/lanreotide of 40, 12 and 260, respectively, pH 1-2 with an incubation at 100 degrees C for 30 min. Quality control evaluation and stability of the radiolabel compound was done by the following selected methods: chromatography in Whatman 3 MM with MEK and NaCl 0.15 M as solvents, ITLC-SG with ethanol-HCl 0.01N (90:10); reverse phase extraction cartridge (Sep-pak C18, Waters Associated) and RP-HPLC with radiometric and UV detection (220 nm) using MCH-5 n-capp column with linear gradient from 90% H2O (TFA 0.1%): 10% ACN (TFA 0.1%) up to 10% H2O (TFA 0.1%):90% ACN (TFA 0.1%) in 30 min, at flow 1 ml/min. Biodistribution in normal mice showed that 188Re-lanreotide is excreted mainly through the hepatobiliary system: more than 70% I.D. is present in gallbladder and intestines at 2 hr post injection. The stability of the 188Re-peptide bond by cysteine challenge test at 37 degrees C, during 2 and 24 hr of incubation time, reveals that approximately 300 and 100 molar ratio cys/peptide is required to displace 50% of the 188Re from the complex. In vitro stability of 188Re-lanreotide at room temperature (Rt) was demonstrated during 24 hr Future works must be done in order to investigate its binding capacity to somatostatin receptors.

Direct radiolabeling of monoclonal antibodies with rhenium-188 for radioimmunotherapy of solid tumors--a review of radiolabeling characteristics, quality control and in vitro stability studies.

188Re is one of the radioisotopes expected to emerge as useful for therapy. Development of new radiopharmaceuticals based on 188Re depends on the radiolabeling methods used, which would give stable complexes having predefined radiochemical properties and in vitro and in vivo stability. This paper has attempted to provide a perspective of 188Re-labeled monoclonal antibodies, their radiolabeling characteristics, methods for quality control of radioimmunoconjugates and in vitro stability for radioimmunotherapy of solid tumors. The direct method of 188Re radiolabeling of antibodies by reductive attachment of 188Re in which free sulfhydryl groups have been generated by reduction of the intramolecular S-S disulfide bonds has been shown to be a promising approach in particular. Moreover, excellent methods have been developed to test the radionuclide, radiochemical purity and stability of 188Re-radioimmunoconjugates using high performance liquid chromatography (HPLC) and paper chromatography.

Experimental determination of dose calibrator settings and study of associated volume dependence in v-vials for rhenium-186 perrhenate solution sources.

OBJECTIVE: Accurate activity measurements of glass conical v-vials are only possible if dose calibrator dial settings are experimentally determined for the specific vial and volume range over which the measurements of a particular radionuclide is to be made. V-vials are used to transport and store unit doses of radiopharmaceuticals containing high-energy beta-emitters, such as 186Re. We have determined the correct dose calibrator dial settings for measuring 186Re in 3-mL glass conical v-vials from 2 manufacturers. METHODS: The 186Re solutions used were calibrated for radioactivity content at the National Institute of Standards and Technology (NIST) using liquid scintillation counting with 3H-standard efficiency with a maximum expanded (k = 2) uncertainty of 1.2% on the activity. Volumes of the solutions then were accurately dispensed into a set of v-vials from each of the 2 manufacturers and assayed in the dose calibrator maintained at NIST. RESULTS: For filling volumes above 1 mL, the dose calibrator response was found to be constant for both of the vials studied, enabling a single dial setting to be used for each vial type. The expanded uncertainties on the activity from uncertainty in the dial setting in that volume range were 0.4%-0.7%. Variability in vial construction contributed another 0.2%-0.3% in the uncertainty in the activity determination. CONCLUSION: These studies indicate a strong volume dependence on the response of the dose calibrator and highlight the need for experimental verification of dose calibrator settings for nonstandard geometries.

A new experimental determination of the dose calibrator setting for 188Re.

UNLABELLED: Accurate activity measurements of radionuclides using commercial dose calibrators requires that the correct dial setting (or calibration factor) be applied. The dose calibrator setting for the medical radionuclide 188Re (as 188ReO4-) has been determined experimentally using solution sources prepared and calibrated at the National Institute of Standards and Technology (NIST). METHODS: The specific activity of two sources (in units of MBq/g) in the standard 5-mL NIST ampoule and in a 5-mL SoloPak dose vial were calibrated using 4pibeta liquid scintillation counting with 3H-standard efficiency tracing and gamma-ray/bremmstrahlung counting in the NIST "4pi" gamma ionization chamber on gravimetrically related sources. RESULTS: The newly determined settings for the NIST Capintec CRC-12 dose calibrator are (631+/-4) x 10 and (621+/-3) x 10 for the respective ampoule and dose vial geometries with an expanded (at a presumed 95% confidence level) uncertainty of 0.4%-0.5% in the activity determination. The setting for the dose vial geometry was independently confirmed using a Capintec CRC-15R at Cedars-Sinai Medical Center using sources calibrated against a NIST standard. CONCLUSION: These new settings result in activity readings 28%-30% lower than those obtained using the previously recommended setting of 496 x 10. This discrepancy most likely results from underestimating the total radiation yield from 188Re decay when calculating the dose calibrator response. This study emphasizes the need for experimental determinations of dose calibrator settings in the geometry in which the measurements will be performed.

National radioactivity standards for beta-emitting radionuclides used in intravascular brachytherapy.

The uses of beta-particle emitting radionuclides in therapeutic medicine are rapidly expanding. To ensure the accurate assays of these nuclides prior to administration, radioactivity standards are needed. The National Institute of Standards and Technology (NIST), the national metrological standards laboratory for the United States, uses high-efficiency liquid scintillation counting to standardize solutions of such beta emitters, including 32P, 90Sr/90Y, and 188Re. Additional measurements are made on radionuclidic impurities, half lives, and other decay-scheme parameters (such as branching decay ratios or gamma-ray abundances) using HPGe detectors and reentrant ionization chambers. Following such measurements at NIST, standards are disseminated in three ways: Standard Reference Materials (SRMs), calibrations for source manufacturers, and calibration factors for commercial instruments. Uncertainties in the activity calibrations for these nuclides are of the order of +/-0.5% (at approximately 1-standard deviation confidence intervals).