International Journal of Nuclear Medicine Research  (Special Issue - 2017)
 188Re Zoledronic Acid in the Palliative Treatment of Painful Bone Metastases Nuclear
Pages 92-100

Tatiana Kochetova, Valeriy Krylov, Maxim Smolyarchuk, Dmitriy Sokov, Alexander Lunev, Sergey Shiryaev, Olga Kruglova, Tatiana Makeenkova, Karina Petrosyan, Alexandra Dolgova, Marina Poluektova, Vsevolod Galkin and Andrey Kaprin

DOI: http://dx.doi.org/10.15379/2408-9788.2017.08

Published: 31 July 2017

Abstract

188Re Zoledronic acid (188Re-ZA) is new radiopharmaceutical which may have advantages over other bone seeking β-emitters due to high radiation energy of 188Re, and metabolic effect of zoledronic acid.

In the phase I-II of the study therapeutic dosage of 188Re-ZA was estimated. Pharmacokinetics, dosimetry and safety were assessed in the dose escalation study. Twenty-one (3, 3 and 15) breast and prostate cancer patients with multiple painful bone metastases received 35, 45 and 55 MBq of 188Re-ZA respectively. In the next step 42 new patients were randomized in 2 groups (188Re-ZA in dosage of 45 MBq/kg and 89SrCl2 in dosage of 150 MBq) to assess safety and efficacy of the radiopharmaceuticals, the follow up lasted for 9 weeks.

Absorbed dose to the bone marrow is respectively low 0.26±0.06 Gy. The dose escalation study shows that 188Re-ZA the dosage of 55 MBq/kg is safe, no significant hematologic or any other toxicity is observed. 89SrCl2 in a dosage of 150 MBq, as compared to 188Re-ZA in a dosage of 45 MBq/kg demonstrates similar efficacy, but the effect starts faster in 188Re-ZA group. By the end of the follow up some patients demonstrated pain recurrence, this may indicate the need for repeated courses of treatment. Though many patients with widespread bone metastases and the higher base level of alkaline phosphatase were in the 188Re-ZA group, in the majority of cases of both groups stabilization of the disease was achieved and continued for at least two months. Both radiopharmaceuticals demonstrated acceptable safety profile. Although trend in reduction of hemoglobin level was observed, especially in the group of patients with baseline anemia, both radiopharmaceuticals significantly impact on the platelet counts (PLT) only. As it was predicted by dosimetry data, 188Re-ZA in a dose of 45 MBq/kg is safer, by the week 6 the PLT counts in the 188Re-ZA group became almost the same as baseline and even higher in the week 9, while in the 89SrCl2 group in the week 9 PLT counts remained below the baseline; the difference was statistically proven. It seems that patients with breast cancer, in contrast to those with prostate cancer, have benefit (not statistically significant) in overall survival: 20.7 vs 15.6 months regardless dosage or type of radiopharmaceutical.

Keywords
Bone metastases, 188Re-Zoledronic acid, Radiopharmacy, 153Sm-EDTMP, 89SrCl2.
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