pH-Responsive Carboxymethylcellulose Nanoparticles for 68Ga-WBC Labeling in PET Imaging.

Carboxymethylcellulose (CMC) is a well-known pharmaceutical polymer, recently gaining attention in the field of nanomedicine, especially as a polyelectrolyte agent for the formation of complexes with oppositely charged macromolecules. Here, we report on the application of pH-sensitive pharmaceutical grade CMC-based nanoparticles (NP) for white blood cells (WBC) PET imaging. In this context and as an alternative to 99mTc-HMPAO SPECT labeling, the use of 68Ga3+ as PET radionuclide was investigated since, at early time points, it could provide the greater spatial resolution and patient convenience of PET tomography over SPECT clinical practices. Two operator-friendly kit-type formulations were compared, with the intention of radiolabeling within a short time (10 min), under mild conditions (physiological pH, room temperature) and in agreement with the actual clinically applied guidelines. NP were labeled by directly using 68Ga3+ eluted in HCL 0.05 N, from hospital suited 68Ge/68Ga generator and in absence of chelator. The first kit type approach involved the application of 68Ga3+ as an ionotropic gelation agent for in-situ forming NP. The second kit type approach concerned the re-hydration of a proper freeze-dried injectable NP powder. pH-sensitive NP with 250 nm average diameter and 80% labeling efficacy were obtained. The NP dispersant medium, including a cryoprotective agent, was modulated in order to optimize the Zeta potential value (-18 mV), minimize the NP interaction with serum proteins and guarantee a physiological environment for WBC during NP incubation. Time-dependent WBC radiolabeling was correlated to NP uptake by using both confocal and FT-IR microscopies. The ready to use lyophilized NP formulation approach appears promising as a straightforward 68Ga-WBC labeling tool for PET imaging applications.

Miniaturized Radiochemical Purity Testing for 99mTc-HMPAO, 99mTc-HMDP, and 99mTc-Tetrofosmin.

Quick methods are functional in clinical practice to ensure the fastest availability of radiopharmaceuticals. For this purpose, we investigated the radiochemical purity of the widely used 99mTc-hydroxymethylene diphosphonate, 99mTc-hexamethylpropyleneamine oxime, and 99mTc-tetrofosmin by reducing time as compared with the manufacturer's method. Methods: We applied a miniaturized chromatographic method with a reduced strip development from 18 cm to 9 cm for all 3 radiopharmaceuticals. The specific support medium and solvent system of the manufacturer's methods was kept unchanged for 99mTc-hydroxymethylene diphosphonate and 99mTc-tetrofosmin, whereas for 99mTc-hexamethylpropyleneamine oxime the instant thin-layer chromatography (ITLC) polysilicic gel (silicic acid [SA]) was replaced with a monosilicic gel (silicic gel [SG]) in the chromatographic system that uses methyl ethyl ketone as solvent. The method was applied and compared with the routine ITLC insert method in a total of 30 batches for each radiopharmaceutical. The precision of repeated tests was determined by comparison with the results of 10 replications on the same batch. Small volumes of concentrated 99mTcO4-, and 99mTc-albumin nanocolloid were used to produce potential radiochemical impurities. Correlation between the quick methods and the insert methods was analyzed using a nonparametric 2-tailed test and a 2 × 2 contingency table with the associated Fisher exact test to evaluate sensitivity and specificity. A receiver-operating-characteristic analysis was performed to evaluate the best cutoff. Results: The percentage radiochemical purity of the quick methods agreed with the standard chromatography procedures. We found that 99mTcO4 and colloidal impurities are not the only common radiochemical impurities with 99mTc-tetrofosmin, and shortening of the ITLC strip with respect to the manufacturer's method will worsen system resolution and may produce inaccuracy. Conclusion: The miniaturized methods we described represent a fast and reliable alternative for 99mTc-exametazime and 99mTc-oxidronate quality control, with the upper cutoff for acceptable radiochemical purity values being 84% and 95%, respectively. For 99mTc-tetrofosmin radiochemical purity testing, a longer strip as described in the standard method is warranted.

111In-DTPA-Biotin uptake by Staphylococcus aureus.

The potential of indium-111 labelled diethylenetriaminepentaacetic acid α,ω-bis(biocytinamide) (In-DTPA-Biotin) as a specific tracer in nuclear medicine imaging of vertebral osteomyelitis has been shown in a large series of consecutive patients. Biocytin is known to serve as a biotin source for a number of different microorganisms and quantitative studies on staphylococci indicated that on a molar basis biocytin seemed to have an activity equal to that of biotin. In this study, we evaluated the possibility of an illicit transport of In-DTPA-Biotin in cultures of Staphylococcus aureus on continued incubation for 24 h. Radiolabelled biocytin was prepared as described earlier and the stability and radiochemical purity was assessed in vitro for 24 h after labelling. Our data seem to demonstrate a passive transport of In-DTPA-Biotin into the cells of the microorganisms.