DIVALENT COBALT AS A LABEL TO STUDY LYMPHOCYTE DISTRIBUTION USING PETAND SPECT

PET and SPECT allow the study of the distribution of lymphocytes in li ving humans, provided that these cells are adequately prelabeled ex vi vo. Such a labeling technique should not only be nontoxic to lymphocyt es but it also should take into consideration that their kinetics are such that radioactivity must be followed for at least 24 hr. We descri be the potential of divalent cobalt isotopes (Co-55(2+), half-life 17. 5 hr for PET; Co-57(2+), half-life 270 days for SPECT) for labeling ly mphocytes. Methods: Isolated rat lymphocytes were incubated with (CoCl 2)-Co-57 with or without unlabeled CoCl2 or CaCl2 carrier or other com pounds. In some experiments, the accumulation of radioactive cobalt an d calcium in lymphocytes was determined in the presence of phorbol myr istate acetate alone, calcimycine alone or in combination. The toxicit y of cobalt to lymphocytes was assessed with the trypan blue exclusion test and by assessing their proliferative capacity using radioactive thymidine incorporation as a readout. Biodistribution of cobalt-labele d lymphocytes was determined with postmortem analysis and compared wit h that of the free (nonlymphocyte-bound) tracer. Results: At high conc entrations (more than 100 x necessary for adequate labeling), cobalt w as not cytotoxic. Incubation of labeled lymphocytes in tissue culture medium for 24 hr in vitro showed a loss of less than half of the incor porated cobalt radioactivity. Twenty-four hours after in vitro labelin g of lymphocytes and intravenous injection, radioactivity accumulated not only in the liver, kidney and bladder of the rat but in the spleen and lungs, which differed from the distribution of the free tracer. U ptake and binding to rat lymphocytes of Co2+ partly mimicked that of C a2+. The binding of cobalt, however, was stronger and nonsaturable. Co nclusion: These results warrant further exploration of cobalt as a PET or SPECT label of human lymphocytes.