Re-HEDP : pharmacokinetic characterization, clinical and dosimetric evaluation in osseous metastatic patients with two levels of radiopharmaceutical dose

BACKGROUND: A study for pain relief therapy with (188)Re-HEDP was done in patients with bone metastases secondary to breast and prostate cancer. MATERIALS AND METHODS: Patients received 1.3 or 2.2 GBq, in single or multiple doses. Platelets, white and red cells were evaluated during 11 weeks. Pharmacokinetic characterization was done from blood and urine samples for 5 patients along 24 hours. Urinary excretion was evaluated in other 16 patients during 6 hours. Bone uptake was estimated as remaining activity in whole body. Scintigraphic images were acquired at 2 and 24 hs post-administration. Absorbed dose in bone marrow was estimated with Mirdose3. Analgesics intake and pain score were daily recorded. Tumour markers (PSA, and Tn-structure) were monitored in 9 patients during 4 to 6 months. Single doses of low activity (1.3 GBq) were given to twelve patients. Nine patients received multiple doses. RESULTS: All except one patient had normal levels of platelets, white and red cells. Remaining dose in blood at 2 hours was 9%. Urinary elimination was 58%. Bone uptake at 24 hours was 43% (mean value; n = 5). No changes of the haematological parameters were detected along follow-up period. Pain relief was evidenced by decrease or supression of opioid analgesic and by subjective index. PSA showed a decrease in prostate cancer patients (n = 4). Tn-structure showed a significant increase after 4 to 8 months. CONCLUSION: Single or multiple dose scheme could be safely used, with administered activity of (188)Re-HEDP up to 60 mCi, with low bone marrow absorbed doses

Palliation of Metastatic Bone Pain with Radiolabeled Phosphonates

This chapter reviews the role of various radiolabeled phosphonates in the palliation of bone pain from osteoblastic metastatic and primary bone disease. Various radiophosphonates are available for this purpose. These include Samarium-153 ethylenediaminetetramethylenephosphonate (Samarium-153 EDTMP), Rhenium-188 hydroxyethylidenediphosphonate (Rhenium-188 HEDP), and Lutetium-177 ethylenediaminetetramethylene phosphonic acid (Lutetium-177 EDTMP). They generally have comparatively short physical half-lives and high dose rates and can be administered as either monotherapy or fractionated therapy with low toxicity. They also can be imaged to both assess efficacy and conduct dosimetry studies. One agent that has been studied extensively and approved for bone palliation in a variety of cancers, including prostrate, breast, lung, and other primary cancers, is Samarium-153 EDTMP. It has been shown to be effective with single-dose treatment in 65–85% of patients, with pain relief seen within 4–6 weeks of treatment. Initial positive responses have been sustainable over longer periods, with significant reduction in opioid and other analgesic needs, overall improvement in quality of life, and survival benefits with minimal short- and long-term adverse events. Additionally, more recent studies have demonstrated that it can be safe to combine Samarium-153 EDTMP with chemotherapy, external beam radiation therapy, and nonradioactive bisphosphonates, to palliate metastatic bone pain and provide an antitumor strategy especially for metastatic castration-resistant prostate cancer. More recently, studies have shown that Rhenium-188 HEDP holds promise because it appears to be effective in rapidly relieving pain and improving overall survival in patients with prostate cancer when given as repeated therapy, it is readily available from a generator, and it is cost-effective