Rhenium is a member of the same Family VIIA of the Periodic Table as Tc, and their chemical properties are predictably quite similar, although Re is more easily oxidized to the perrhenate than Tc is to pertechnetate. To take advantage of the beta-emitting characteristics of Re-186 (and Re-188, described in Table 1), Re-186 etidronate was synthesized. This compound has the same affinity for bone as the Tc-99m etidronate analog, as well as all the other radiopharmaceuticals under discussion. Because Re-186 is more easily reoxidized, one finds this radionuclide in the urine of patients receiving it for a longer period than with Sm-153-lexidronam. Similar to Sm-153 lexidronam, this compound appears to chemisorb to bone, through coordination with the oxygen atoms, and also forms a rhenium oxide compound on the hydroxyapatite surface. While not approved for use in the United States, it is widely employed in Europe. The early studies on Re-186 etidronate suggested response rates as high as 77%, but with more rigorous criteria, the Utrecht group has published response rates closer to 55% for both painful metastatic breast and prostate cancer. Using the tridimensional analysis referred to before, the Utrecht group found a response rate of 6/18 at 35 mCi, 7/9 at 50-60 mCi, and 7/10 at 80-95 mCi. Pain reduction was counted as significant only if it lasted at least two weeks. Fifty-four percent of the patients met this criterion, but only 35% of responses lasted four weeks. As with the rest of the radiopharmaceuticals under discussion, there is a threshold of efficacy beyond which higher doses lead only to greater toxicity but not to greater pain relief. Thirteen studies of Re-186 etidronate which have been analyzed reveal response rates ranging between a low of 54% and a high of 87%, close to the 90% found in the IAEA study of P-32 and Sr-89. It is clear that the stricter the criteria one employs, especially taking into account the changes in activities of daily living and medication for each patient following injection, the lower the response rate observed.
A small double-blind crossover study established that Re-186 etidronate is more active than placebo. A more recent published comparison of Sr-89 and Re-186 etidronate found no difference in response rates, 84% for the former, 92% for the latter, with no difference found also in the mean duration of pain relief, 125 days with Sr-89 and 107 days with Re-186 etidronate. Myelotoxicity was also similar, but platelet and leukocyte counts returned to baseline by six weeks after Re-186 etidronate and 12 weeks after Sr-89, a statistically significant difference.
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