Sterility assurance of technetium-99m radiopharmaceuticals: no specific air conditions are required for their preparation, storage and dispensation.

BACKGROUND: The aim of this study was to ascertain whether the extemporaneous technetium-99m radiopharmaceuticals - prepared by closed procedures - maintain or not sterility throughout their lifespan regardless the quality of the environmental air where they are prepared, stored and dispensed, provided that the basic aseptic rules for closed procedures are followed. METHODS: Three different types of assays were performed in this study: 1) sterility tests of each and every one of the vials with the remains of technetium-99m radiopharmaceuticals, which have been prepared in our hospital radiopharmacy during three years without any special environmental air conditions; 2) integrity tests of punctured rubber plug closures using both microbial challenge testing and dye ingress testing; and 3) simulation of the dispensing process using a liquid growth medium. RESULTS: Sterility tests of more than 6,000 vials with the remains of technetium-99m radiopharmaceuticals - prepared without any special ambient air conditions - were performed, all of them with a negative result (no growth of microorganisms occurs). The integrity of punctured rubber plugs closure was sufficiently proven under extreme conditions by two different methods. The maintenance of sterility during the dispensing process of technetium-99m radiopharmaceuticals was also proven by simulation of the dispensing process using a liquid growth medium. CONCLUSIONS: This study strongly supports that it is not necessary any special ambient air conditions to prepare, store and dispense extemporaneous technetium-99m radiopharmaceuticals in order to preserve their sterility when the basic aseptic rules for closed procedures are followed.

Modulated selection of IGHV gene somatic hypermutation during systemic maturation of human plasma cells.

Systemic antigen-induced PCs are generated in inductive lymphoid tissues. Some of them are selected to travel through the circulation and finally, to home onto BM niches. BM PCs show prolonged survival and secrete high-affinity antibodies. In this study, human PCs were isolated from tonsil, blood, and BM, their IGHV3 and IGHV6 genes were sequenced, and their SHM were evaluated. The SHM analysis reveals the existence of a maturational gradient in these genes, as demonstrated by a progressive increase in the frequency of total and R mutations and total and NC aa changes following the direction: tonsil --> blood --> BM. The ratio of R to S mutations in the CDR1 and -2, but not in the FRs, increases from tonsil to blood and BM; this parameter reaches a maximum threshold when more than 10 mutations/sequence occur. Further analyses indicate that CDR1 and CDR2 SHM followed different strategies to provide appropriate amino acid changes, but both exhibited maximal resistance to incorporating drastic molecular alterations in the BM PCs. Finally, all of the findings are similar in IGHV3 and IGHV6 sequences, indicating that they reflect general rules imposed by in vivo antigen selection.