[en] A simple and rapid procedure was developed for purification of cyclotron produced ⁸⁶Y via the ⁸⁶Sr(p,n) ⁸⁶Y reaction. A commercially available Sr(II) selective resin was used to separate ⁸⁶Y from the cyclotron irradiated Sr(II) target with a recovery of the enriched Sr(II) target while yielding a 75-80% recovery of ⁸⁶Y suitable for radiolabeling either proteins or peptides. To demonstrate the utility of this methodology, the anti-HER2 monoclonal antibody Herceptin^TM was radiolabeled with the purified ⁸⁶Y and compared to ¹¹¹In labeled Herceptin^TM. The biodistribution study demonstrated that ¹¹¹In-Herceptin^TM, while a suitable surrogate for ⁹⁰Y in the major organs, did not parallel the uptake of ⁸⁶Y-Herceptin^TM in the bone, and thus may not accurately predict the level of ⁹⁰Y accumulation in the bone for clinical RIT applications. This result exemplifies the requirement of employing appropriate matched pair isotopes for imaging and therapy to insure that dosimetry considerations may be addressed accurately

[en] Recycling of [¹⁸O]water for [¹⁸F]fluoride production can be accomplished with reliable results. We have developed sensitive, robust, and rapid analyses of impurities in [¹⁸O]water. Anions were quantitated by capillary electrophoresis and organic residuals were quantitated by gas chromatography using methods with excellent reproducibility and linearity. Kryptofix 222 (K-222) was quantitated by a sensitive LC-MS-MS technique. Isotopic composition was determined by GC-MS with satisfactory accuracy and precision. These methods were employed to evaluate recovered [¹⁸O]water purified by a novel electrolysis method. 2-[¹⁸F]FDG yields using purified [¹⁸O]water with very low levels of impurities are indistinguishable from newly purchased [¹⁸O]water. High (> 300 ppm) carbonate concentration reduces the fluoride trapping efficiency of QMA. The analyses of anions, organics, and isotopic enrichment were applied routinely for quality control of [¹⁸O]water to predict a satisfactory outcome of 2-[¹⁸F]FDG production

[en] The separation of ⁸⁶Y from ⁸⁶Sr was optimized by a semi-automated purification system involving the passage of the target sample through three sequential columns. The target material was dissolved in 4 N HNO₃ and loaded onto a Sr-selective (Sr-Spec) column to retain the ⁸⁶Sr. The yttrium was eluted with 4 N HNO₃ onto the second Y-selective (RE-Spec) column with quantitative retention. The RE-Spec column was eluted with a stepwise decreasing concentration of HNO₃ to wash out potential metallic impurities to a waste container. The eluate was then pumped onto an Aminex A5 column with 0.1 N HCl and finally with 3 N HCl to collect the radioyttrium in 0.6-0.8 mL with a >80% recovery. This method enabled us to decontaminate Sr by 250,000 times and label 30 μ g of DOTA-Biotin with a >95% yield

[en] A simple and rapid procedure was developed for the purification of cyclotron-produced ²⁰³Pb via the ²⁰³Tl(d,2n) ²⁰³Pb reaction. A Pb(II) selective ion-exchange resin, with commercial name Pb Resin from Eichrom Technologies, Inc., was used to purify ²⁰³Pb from the cyclotron-irradiated Tl target with excellent recovery of the enriched Tl target material. The purified ²⁰³Pb was used to radiolabel the monoclonal antibody Herceptin. The in vitro and in vivo properties of the ²⁰³Pb radioimmunoconjugate were evaluated

[en] Multi-instrument activity estimation and decay correction techniques were developed for radionuclide mixtures, motivated by the desire for accurate quantitation of Tc-94m positron emission tomography (PET) studies. Tc-94m and byproduct Tc isotopes were produced by proton irradiation of enriched Mo-94 and natural Mo targets. Mixture activities at the end of bombardment were determined with a calibrated high purity germanium detector. The activity fractions of the greatest mixture impurities relative to 100% for Tc-94m averaged 10.0% (Tc-94g) and 3.3% (Tc-93) for enriched targets and 10.1% (Tc-94g), 11.0% (Tc-95), 255.8% (Tc-96m), and 7.2% (Tc-99m) for natural targets. These radioisotopes have different half-lives (e.g., 52.5 min for Tc-94m, 293 min for Tc-94g), positron branching ratios (e.g., 0.72 for Tc-94m, 0.11 for Tc-94g) and gamma ray emissions for themselves and their short-lived, excited Mo daughters. This complicates estimation of injected activity with a dose calibrator, in vivo activity with PET and blood sample activity with a gamma counter. Decay correction using only the Tc-94m half-life overestimates activity and is inadequate. For this reason analytic formulas for activity estimation and decay correction of radionuclide mixtures were developed. Isotope-dependent sensitivity factors for a PET scanner, dose calibrator, and gamma counter were determined using theoretical sensitivity models and fits of experimental decay curves to sums of exponentials with fixed decay rates. For up to 8 h after the end of bombardment with activity from enriched and natural Mo targets, decay-corrected activities were within 3% of the mean for three PET studies of a uniform cylinder, within 3% of the mean for six dose calibrator decay studies, and within 6% of the mean for four gamma counter decay studies. Activity estimation and decay correction for Tc-94m mixtures enable routine use of Tc-94m in quantitative PET, as illustrated by application to a canine Tc-94m sestamibi study

[en] Significant improvement of in vivo stability of ²¹¹At-labeled radioimmunoconjugates achieved upon employment of a recently reported new linker, succinimidyl N-2-(4-[²¹¹At]astatophenethyl)succinamate (SAPS), prompted additional studies of its chemistry. The ²¹¹At radiolabeling of succinimidyl N-2-(4-tributylstannylphenethyl)succinamate (1) was noted to decline after storage at -15^oC for greater than 6 months. Compound 1 was found to degrade via a ring closure reaction with the formation of N-2-(4-tributylstannylphenethyl)succinimide (3), and a modified procedure for the preparation of 1 was developed. The N-methyl structural analog of 1, succinimidyl N-2-(4-tributylstannylphenethyl)-N-methyl succinamate (SPEMS), was synthesized to investigate the possibility of improving the stability of reagent-protein linkage chemistry. Radiolabeling of SPEMS with ²¹¹At generates succinimidyl N-2-(4-[²¹¹At]astatophenethyl)-N-methyl succinamate (Methyl-SAPS), with yields being consistent for greater than 1 year. Radiolabelings of 1 and SPEMS with ¹²⁵I generated succinimidyl N-2-(4-[¹²⁵I]iodophenethyl)succinamate (SIPS) and succinimidyl N-2-(4-[¹²⁵I]iodophenethyl)-N-methyl succinamate (Methyl-SIPS), respectively, and showed no decline in yields. Methyl-SAPS, SAPS, Methyl-SIPS and SIPS were conjugated to Herceptin for a comparative assessment in LS-174T xenograft-bearing mice. The conjugates of Herceptin with Methyl-SAPS or Methyl-SIPS demonstrated immunoreactivity equivalent to if not superior to the SAPS and SIPS paired analogs. The in vivo studies also revealed that the N-methyl modification resulted in a superior statinated product

[en] A method for assessing the impurity ²¹⁰At in cyclotron-produced ²¹¹At via isotope dilution alpha spectrometry is presented. The activity of ²¹⁰At is quantified by measuring the activity of daughter nuclide ²¹⁰Po. Counting sources are prepared by spontaneous deposition of Po on a silver disc. Activity of ²¹⁰At (at the time of ²¹⁰Po maximum activity) is found to be 83.5+/-9.0Bq, corresponding to an atom ratio (²¹⁰At:²¹¹At at the time of distillation) of 0.010+/-0.007% (k=2). The method produces high-quality alpha spectra, with baseline alpha-peak resolution and chemical yields of greater than 85%

[en] The syntheses, radiolabeling, antibody conjugation and in vivo evaluation of new linkers for ²¹¹At labeling of monoclonal antibodies are described. Syntheses of the N-succinimidyl esters and labeling with ²¹¹At to form succinimidyl 4-methoxymethyl-3-[²¹¹At]astatobenzoate (9) and succinimidyl 4-methylthiomethyl-3-[²¹¹At]astatobenzoate (11) from the corresponding bromo-aryl esters is reported. Previously reported succinimidyl N-{4-[²¹¹At]astatophenethyl}succinamate (SAPS) is employed as a standard of in vivo stability. Each agent is conjugated with Herceptin in parallel with their respective ¹²⁵I analogue, succinimidyl 4-methoxymethyl-3-[¹²⁵I]iodobenzoate (10), succinimidyl 4-methylthiomethyl-3-[¹²⁵I]iodobenzoate (12) and succinimidyl N-{4-[¹²⁵I]iodophenethyl}succinamate (SIPS), respectively, for comparative assessment in LS-174T xenograft-bearing mice. With 9 and 11, inclusion of an electron pair donor in the ortho position does not appear to provide in vivo stability comparable to SAPS. Variables in radiolabeling chemistry of these three agents with ²¹¹At are notable. Sequential elimination of acetic acid and oxidizing agent, N-chlorosuccinimide (NCS), from the ²¹¹At radiolabeling protocol for forming SAPS improves yield, product purity and consistency. NCS appears to be critical for the radiolabeling of 6 with ²¹¹At. Formation of 11, however, is found to require the absence of NCS. Elimination of acetic acid is found to have no effect on radiolabeling efficiency or yield for either of these reactions