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Objective To study the tolerance to 188Re-1-hydroxy-1 ,1-ethylidene disodium phosphonate(HEDP) in patients with bone pain caused by osseous metastases. Methods Thirty-one patients(10with prostate cancer, 9 with breast cancer, 3 with lung cancer, 5 with liver cancer, 2 with rectal cancer, 1with esophageal cancer and 1 with renal cancer) received a single injection dose of 188Re-HEDP. The patients were divided into four groups according to the injection dose: 20 MBq/kg (6 patients), 30 MBq/kg(6 patients), 40 MBq/kg (9 patients), and 50 MBq/kg (10 patients). Haematological toxicity (WHO grading) of grade Ⅲ- Ⅳ was considered unacceptable. Vital signs and adverse effects after injection were recorded for 8 weeks. Blood counts were measured weekly during a period of 8 weeks. Biochemical parameters and electrocardiogram were assayed at week 4 and 8. Statistical analysis was performed for per-protocol (pp) population (t-test). Results Twenty-seven patients belonged to PP population with 5 in the group of 20 MBq/kg, 5 in the group of 30 MBq/kg, 8 in the group of 40 MBq/kg and 9 in the group of 50 MBq/kg.No obvious adverse effects and no significant change of vital signs, electrocardiogram, liver and renal function were found after injection. Alkaline phosphatase was slightly higher than baseline at week 4 and 8 after therapy, but the difference was not statistically significant. In the 20 MBq/kg group, reversible grade Ⅰ leucopenia was noted in 1 patient. In the 30 MBq/kg group, 2 patients showed reversible grade Ⅰ leucopenia including 1 alone with reversible grade Ⅲ thrombopenia. In the 40 MBq/kg group, reversible grade Ⅰ leucopenia and thrombopenia was observed in 1 patient and reversible grade Ⅱ leucopenia and thrombopenia in another patient. In the .50 MBq/kg group, 3 patients showed reversible grade Ⅱ leucopenia. The lowest level of thrombopenia was at week 4(143.5 × 109/L), leucopenia at week 6 (5.4 × 109/L) and anaemia at week 8(t = 3.1325, 3.3156, 3.4917, all P ＜ 0. 05 compared with baseline). At week 8, the mean level of platelet and leucocyte recovered to baseline. "Bounce pain" was found in 2 of 27 patients (7.41%).Conclusions The dose of 20 MBq/kg, 30 MBq/kg, 40 MBq/kg or 50 MBq/kg of 188Re-HEDP do not cause significant side effects on cancer patients with bone metastases, though there is a tendency that the haematological toxicity may increase as the dose of 188Re-HEDP increases.
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Objective To investigate the biodistribution,excretion and other pharmacokinetics,of 188Re-1-hydroxy-1,1-ethylidene disodium phosphonate (HEDP) in cancer patients with osseous metastases who were suffering form bone pain. Methods A single dose (20,30,40,and 50 MBq/kg,10 patients in every group) of 188Re-HEDP was administered as a bolus injection,meanwhile dynamic images on patient's chest were collected for 30 min. Anterior and posterior whole-body images were obtained at 1,2,4,5,12,24,36,48,60 and 72 h after injection of 188Re-HEDP. By region of interest (ROI) technology,the curve of time-background corrected counts of left cardiac ventricle could be generated,and the background-corrected counts of various organs and total whole body could be calculated as a geometric mean using the anterior and posterior scans,and transformed to the percentage injected dose ( % ID). Urine was collected after injection of 188Re-HEDP. Counts of urine were measured by γ counter. Analysis of variance and t-test were used. Results Linear relationship of metabolism of 188Re-HEDP was observed in the doses from 20 to 50 MBq/kg,with correlation coefficient r2 = 0. 9376. A two-compartment model was the best fit for metabolism of 188Re-HEDP with the parameters median area under curve (AUC) 3.32 × 105,3.97 × 105,7.83 × 105,8.58 ×105,respectively; median α 0.06,0.05,0.04,0.06 respectively; median β 1.16 ×10-3,1.16 × 10-3,1.03 × 10-3,1.15 × 10 -3 respectively; median A 3591.21,4858.23,5642. 48,4167.05 respectively; median B 293.97,352.95,614.41,1063.82 respectively; median T1/2(α) 12.51,12.83,15.41,12.02 min respectively; median T1/2(β) 595.47,596.50,673.09,600.93 min respectively in the doses of 20,30,40and 50 MBq/kg. 188Re-HEDP was taken up mainly by bone up to 40% ID at 4 h. Urine profile showed that 66.79 % ID was eliminated within 24 h,being its 74% collected along the first 5 h after-administration.Conclusions In the doses of 20,30,40 and 50 MBq/kg,metabolism of 188Re-HEDP presented linear model. Pharmacokinetics of 188 Re-HEDP followed a two-compartment model administrated by blood vessel.Following injection,188 Re-HEDP was taken up mainly by bone and excreted by uropoietic system.
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PURPOSE: Re-188-Hydroxyethylidene diphosphonate (HEDP) is a new cost-effective agent for systemic radioisotope therapy of metastatic bone pain. We investigated the influence of carrier for labeling and biodistribution of Re-188-HEDP using HEDP kit with or without carrier (KReO4). MATERALS AND METHODS: The kits (HEDP 15 mg, gentisic acid 4 mg and SnCl2.2H2O 4.5 mg) with or without carrier (KReO4 0.1 mg) were labeled with Re-188 solution, made available from an in-house generator by boiling for 15 min. We compared the labeling efficiency and stability of carrier-added and carrier-free preparations of Re-188-HEDP. Biodistribution and imaging studies of each preparation were performed in ICR mice (1.85~3.7 MBq/0.1 ml) and SD rats (74.1~85.2 MBq/0.5 ml). RESULTS: The carrier-added preparation showed high labeling efficiency (95% at pH 5) and high stability in serum (88%, 3 hr). However, the carrier-free preparation showed low labeling efficiency (59% at pH 5) and low stability (43%, 3 hr). The carrier-added preparation showed high uptake in bone and low uptake in stomach and kidneys. However, the carrier-free preparation showed lower uptake in bone and higher uptake in both stomach and kidneys, which is supposed to be due to released perrhenate. The carrier-added preparation also showed better images with higher skeletal accumulation, lower uptake in other organs and lower soft tissue uptake than the carrier-free preparation. CONCLUSION: The results of these studies clearly demonstrate that addition of carrier perrhenate is required for high labeling efficiency, stability, bone uptake and good image quality of Re-188-HEDP.