Target specificity of 188Re-labeled B27.1 monoclonal antibodies to ovarian cancer cells in vivo.

BACKGROUND: Currently we are exploring a new multistep pretargeting approach involving administration of a bispecific antibody (B27.1 x P54) which has an anti-CA-125 (B27.1) and antibiotin (P54) paratope. It is followed by the administration of radiolabeled biotinylated liposomes to target the 188Re to the ovarian cancer cells. As a preliminary step to realize this goal, we determined the target specificity of the monoclonal antibodies (B27.1) to the ovarian cancer cells in vivo. MATERIALS AND METHODS: B27.1 monoclonal antibodies were photoreduced using UV light and incubated with reduced 188Re for 30 min at 25degreesC. 188Re-labeled B27.1 antibodies were purified using size exclusion chromatography. A comparative biodistribution of Re-B27.1 and 188Re was performed in nude mice xenografted with NIH:OVCAR-3 cells. RESULTS: While free rhenium distributed preferentially into thyroid and stomach with insignificant accumulation in the cancer cells, about 20% of the injected dose of 188Re-B27.1 was recovered in ascites cells with insignificant localization in other organs four hours after administration. CONCLUSION: The study validates the affinity of the B27.1 antibodies to the ovarian cancer cells in vivo.

Use of a simulated annealing algorithm to fit compartmental models with an application to fractal pharmacokinetics.

Increasingly, fractals are being incorporated into pharmacokinetic models to describe transport and chemical kinetic processes occurring in confined and heterogeneous spaces. However, fractal compartmental models lead to differential equations with power-law time-dependent kinetic rate coefficients that currently are not accommodated by common commercial software programs. This paper describes a parameter optimization method for fitting individual pharmacokinetic curves based on a simulated annealing (SA) algorithm, which always converged towards the global minimum and was independent of the initial parameter values and parameter bounds. In a comparison using a classical compartmental model, similar fits by the Gauss-Newton and Nelder-Mead simplex algorithms required stringent initial estimates and ranges for the model parameters. The SA algorithm is ideal for fitting a wide variety of pharmacokinetic models to clinical data, especially those for which there is weak prior knowledge of the parameter values, such as the fractal models.

A new and simple calibration-independent method for measuring the beam energy of a cyclotron.

This work recommends a new and simple-to-perform method for measuring the beam energy of an accelerator. The proposed method requires the irradiation of two monitor foils interspaced by an energy degrader. The primary advantage of the proposed method, which makes this method unique from previous energy evaluation strategies that employ the use of monitor foils, is that this method is independent of the detector efficiency calibration. This method was evaluated by performing proton activation of (nat)Cu foils using both a cyclotron and a tandem Van de Graaff accelerator. The monitor foil activities were read using a dose calibrator set to an arbitrary calibration setting. Excellent agreement was noted between the nominal and measured proton energies.

Cyclotron production of (99m)Tc: experimental measurement of the (100)Mo(p,x)(99)Mo, (99m)Tc and (99g)Tc excitation functions from 8 to 18 MeV.

INTRODUCTION: The cyclotron-based (100)Mo(p,2n)(99m)Tc transformation has been proposed as a viable alternative to the reactor based (235)U(n,f)(99)Mo→(99m)Tc strategy for production of (99m)Tc. Despite efforts to theoretically model the amount of ground-state (99g)Tc present at end of bombardment for the (p,2n) reaction, experimental validation has yet to be performed. The co-production of (99g)Tc may have important implications in both the subsequent radiopharmaceutical chemistry and patient dosimetry upon injection. METHODS: To determine the extent of (99g)Tc co-production, we have experimentally measured the (100)Mo(p,x)(99)Mo, (99m)Tc, and (99g)Tc excitation functions in the 8-18 MeV range using a combination of natural abundance and 97.42% enriched (100)Mo foils along with γ-ray spectrometry and ICP-MS. Although the excitation functions for production of (99)Mo and (99m)Tc have been presented previously in the literature, to the best of our knowledge, this work presents the first experimental evaluation of the (100)Mo(p,2n)(99g)Tc excitation function. RESULTS: From the experimental cross-section measurements, the (99m)Tc production yields and (99m)Tc/(99m+g)Tc nuclei ratio were calculated for various thick target irradiation conditions. Results suggest that TBq quantities of (99m)Tc can be achieved with a (99m)Tc/(99m+g)Tc nuclei ratio that is on par with the current (99)Mo/(99m)Tc generator standard eluted at a 24-h frequency. CONCLUSION: These findings suggest that the cyclotron production of (99m)Tc may be a feasible alternative to the current reactor-based production strategy.

A quantitative and comparative study of radionuclidic and chemical impurities in water samples irradiated in a niobium target with Havar vs. niobium-sputtered Havar as entrance foils.

Enriched and natural abundance water samples were irradiated in a niobium (Nb) chamber target with Havar and Nb-sputtered Havar foils. Irradiations were performed with 17.5MeV protons at currents from 35 to 100microA lasting for 1-2.5h. Radionuclidic and chemical (cationic) impurities were determined via gamma spectroscopy and ICP-MS, respectively. Anionic impurities were evaluated by ion chromatography. Impurities in water samples irradiated with the Havar-Nb foils were much lower than the samples irradiated with an unmodified Havar foil. No significant differences were observed in the impurity levels between samples of H(2)(18)O-enriched and natural abundance water. Radionuclidic impurities were observed to decrease after 3-4 irradiations on a fresh Havar entrance foil, and reached a constant value for subsequent irradiations with the same integrated current. For targets covered with Havar foil, radionuclidic impurities were found to be proportional to the beam-integrated current regardless of the beam power and, unexpectedly, dependant of the beam power when using a Havar-Nb foil.