Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous metastases**

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Rhenium-186 (tin)hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in skeletal metastases in patients with advanced cancer. A single intravenous administration of approximately 34 mCi (1,258 MBq) resulted in significant improvement in pain in 33 of 43 evaluable patients (77%) following the initial injection, and in 7 of 14 evaluable patients (50%) following a second treatment. Patients responding to treatment experienced an average decrease in pain of about 60%, with one in five treatments resulting in a complete resolution of pain. The only adverse clinical reaction was the occurrence after about 10% of the administered doses of a mild, transient increase in pain within a few days following injection. Statistically significant but clinically unimportant decreases in total white blood cell counts and total platelet counts were observed within the first 8 weeks following the injection; no other toxicity was apparent. Rhenium-186(Sn)HEDP is a useful new compound for the palliation of painful skeletal metastases.

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      Along with uptake in bone tissue, the biodistribution of 186Re-HEDP involves rapid urinary excretion and rapid blood clearance with a plasma half-life of 41 hours, similar to 99mTc-HMDP. Gamma-camera imaging of 186Re-HEDP and 99mTc-HMDP has demonstrated showed excellent correlation, with 89 % of lesions being detected in both85 Maxon et al 34 performed dosimetry in five patients. Absorbed doses were determined in numerous source and target organs: kidney, bladder wall, skeleton, whole body, red bone marrow and bone metastases.

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      However, bisphosphonates are a prominent class of Re/Tc radiopharmaceuticals, which are currently used in the clinic and thus should be mentioned in this review. These compounds have been known to target bone cancer/metastases for over 30 years and clinical trials are ongoing [175–181]. Specifically, a clinical trial initiated in spring 2018 is currently recruiting patients and involve a combination of 223Ra chloride and 188Re-HEDP treatment.

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      Systemic therapy with radionuclides linked to bone seeking agents is a treatment option for patients with disseminated skeletal metastases, owing to its efficacy, low cost and low toxicity.12 Radionuclides suitable for systemic metabolic radiotherapy of bone pain include Phosphorous-32 (P-32), Strontium-89 (Sr-89), Rhenium-186 (Re-186) chelated with hydroxyethylidene diphosphonate (HEDP) and Samariumm-153 (Sm-153) chelated with ethylenediamine tetramethylene phosphonate (EDTMP).13–16 Considerable bone marrow suppression due to the presence of higher energy β particles is a major constraint toward a widespread use of P-32 (mean β = 695 keV, t1/2 = 14.3 days) and Sr-89 (mean β = 583 keV, t1/2 = 50.5 days).

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    **

    Supported by grants from the National Cancer Institute, National Institutes of Health (CA-32863) and General Clinical Research Center (MO1-RR00068), and through the University Reactor Sharing Program of the Department of Energy for the production of rhenium-186 by the University of Missouri Research Reactor Facility, Columbia, MO.

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