Divalent cobalt as a label to study lymphocyte distribution using PET and SPECT

PET and SPECT allow the study of the distribution of lymphocytes in living humans, provided that these cells are adequately prelabeled ex vivo. Such a labeling technique should not only be nontoxic to lymphocytes but it also should take into consideration that their kinetics are such that radioactivity must be followed for at least 24 hr. We describe 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 lymphocytes. Methods: Isolated rat lymphocytes were incubated with (CoCl2)-Co-57 with or without unlabeled CoCl2 or CaCl2 carrier or other compounds. In some experiments, the accumulation of radioactive cobalt and calcium in lymphocytes was determined in the presence of phorbol myristate acetate alone, calcimycine alone or in combination. The toxicity 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-labeled lymphocytes was determined with postmortem analysis and compared with that of the free (nonlymphocyte-bound) tracer. Results: At high concentrations (more than 100 x necessary for adequate labeling), cobalt was not cytotoxic. Incubation of labeled lymphocytes in tissue culture medium for 24 hr in vitro showed a loss of less than half of the incorporated cobalt radioactivity. Twenty-four hours after in vitro labeling 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. Uptake and binding to rat lymphocytes of Co2+ partly mimicked that of Ca2+. The binding of cobalt, however, was stronger and nonsaturable. Conclusion: These results warrant further exploration of cobalt as a PET or SPECT label of human lymphocytes.