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.

Our objective was to develop a software application that allows us to easily manage a portable database of information on radiopharmaceutical interactions with drugs or other agents and on radiopharmaceutical adverse effects. Methods: The application was developed and compiled with a commercially available data management system and programming language. All data entered into the database came from the scientific literature and were accompanied by their bibliographic references. Results: We developed the database, which we have called Datinrad. To date, it contains 275 drug interactions and 44 records of adverse reactions to radiopharmaceuticals. Conclusion: Datinrad contains all the information published to date on drug-radiopharmaceutical interactions and adverse effects of radiopharmaceuticals and allows users to introduce new data from future publications. The collection of these data and their easy availability to all nuclear medicine personnel will be useful in the recognition of a possible adverse reaction or drug interaction that may alter the radiopharmaceutical biodistribution and lead to a misdiagnosis. This open-access database application is available free of charge in both English and Spanish at www.radiopharmacy.net.A radiopharmaceutical is a pharmaceutical that, when ready for use, incorporates one or more radioactive isotopes. Around 95% of radiopharmaceuticals are used for diagnostic purposes, and the rest are used for treatment of human diseases. Radiopharmaceuticals usually have no pharmacologic effects, as they are used in trace quantities. Thus, significantly unlike conventional drugs, there is no dose-response relationship for radiopharmaceuticals. Even when a radiopharmaceutical is used for therapeutic purposes, the effect achieved is not a pharmacologic consequence but a consequence of radioactivity. However, some exceptions exist, because radiolabeled particles present some potential mechanical issues, such as the embolic effect created by 99m Tc-macroaggregated albumin and 90 Y resin particles or beads. In the case of 99m Tc-macroaggregated albumin, a sufficient number of particles need to be administered to avoid a nonuniform spatial distribution of radioactivity in lung regions; on the other hand, an excess of particles can produce acute toxicity, especially in patients with severe pulmonary hypertension. Therefore, it is important to determine the ideal number of particles for a satisfactory lung scan (1,2). As for 90 Y resin particles or beads, which are used for therapy of primary and metastatic cancer in the liver, their particle size is 20-60 mm and about 20-40 million particles per administration are needed to deliver an equivalent amount of radioactivity into the tumor. These factors increase the probability of blood stasis in the arterial vessel that supplies the tumor during therapy (embolizing effect), as well as the probability of a backflow of spheres into small collateral arteries to the stomach, duodenum, or pancreas. This phenomenon may be eliminated by applying SPECT/C...

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