Dose estimation in strontium-89 radiotherapy of metastatic prostatic carcinoma.

Strontium-89 radiotherapy is becoming an important treatment in the palliation of bone pain from osteoblastic metastases. The absorbed dose delivered to bone metastases during 89Sr radiotherapy has been estimated in four patients with metastatic prostatic carcinoma. Patients were injected with a tracer dose of 85Sr-chloride. Blood and urine samples were obtained during the week following injection. Strontium-85 scintigrams of metastases and normal bone were obtained up to 8 wk postinjection. Half of the patients showed elevated whole-body retention; plasma-strontium concentrations were decreased from normal values. Uptake of strontium in metastases was 2-25 times that in normal bone but rates of washout of strontium from metastases were similar to those from normal bone. Absorbed doses delivered in infinite time to the metastases by 89Sr ranged from 21 +/- 4 to 231 +/- 56 cGy/MBq with a median value of 68 cGy/MBq. Doses to red marrow were less by a factor of 2 to 50. These absorbed doses are sufficiently large to be expected to produce a therapeutic benefit.     

Treatment of metastatic bone pain with repeated doses of strontium-89 in patients with prostate neoplasm

This study has aimed to evaluate the usefulness of repeated treatment with 89Sr in patients with prostate neoplasm and metastatic bone pain. Seventeen patients with partial or complete response after the first dose were retreated with two or more doses (total of 39 doses). The Karnofsky functional status, pain and degree of analgesia were assessed. After the first dose the response was good in 68% of the patients and partial in 32%. After the second dose, the response was good in 62% of the patients, partial in 15% and there was no response in 23% of the cases. The pre-treatment Karnofsky functional status and duration of the effect of 89Sr was lower after the second dose (p = 0.03, p = 0.02), but there were no statistically significant differences in the type of response. In conclusion, re-treatment with 89Sr can be administered safely and with a similar response to that achieved after the first dose.     

Results of strontium-89 therapy in patients with prostate cancer resistant to chemotherapy

PURPOSE: Strontium-89 (Sr-89) chloride is an effective palliative treatment of the bone metastases of prostate cancer. Chemotherapy has also been shown to have a palliative benefit in this disease. We aimed to determine the benefits and complications of Sr-89 therapy in patients with prostate cancer who had become refractory to chemotherapy. We conducted a retrospective review of 14 treatments administered to 13 patients with chemotherapy-resistant and hormone-resistant prostate cancer. RESULTS: Of the 14 administered treatments, 8 (57%) resulted in improved pain control, with 2 patients able to stop analgesia. The median duration of response was 56 days. No prostate-specific antigen response was seen in the 8 patients tested. There was significant and prolonged bone marrow toxicity, with 6 patients requiring red blood cell transfusion. Prolonged thrombocytopenia was seen, with platelet counts remaining below baseline levels after treatment in all but one patient. Leukopenia was generally mild and not associated with infection. CONCLUSIONS: Sr-89 is an effective treatment of patients with chemotherapy-refractory prostate cancer, but careful and prolonged monitoring of hematologic parameters after therapy is required.     

Usefulness of strontium-89 for bone pain palliation in metastatic breast cancer patients

Most studies of prostate cancer have shown that strontium-89 chloride (89Sr) is effective in the palliation of metastatic bone pain, refractory to conventional analgesia. The aim of this study was to evaluate the usefulness of 89Sr for bone pain palliation in breast cancer patients. Forty women were treated with 148 MBq of 89Sr. Six patients were retreated, receiving two or more doses. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. The response was good in 60% of the patients and partial in 32%; there was no response in the remaining 8% (pre-treatment Karnofsky < or = 60). The duration of the response was 120+/-143 days. In the patients retreated, the response was good in 83% and partial in 17%, without significant differences compared with the first dose, but the pre-treatment Karnofsky and the duration of the efficacy were lower (P < 0.05). A transient and slight decrease of leukocyte and platelet counts after the first month of treatment with 59Sr was observed. In conclusion, breast cancer patients with metastatic bone pain can benefit from therapy with 89Sr. If necessary, the treatment may be repeated safely and with the same efficacy as is achieved after the first dose. A low functional performance status could be a cause of the lower effectiveness of 89Sr.     

Indium-111 platelet scintigraphy in a patient with chronic disseminated intravascular coagulation

The authors describe a relation between the in vivo localized consumption of In-111 platelets and results of laboratory tests in a 82-year-old man with an aortic graft prosthesis who had chronic disseminated intravascular coagulation. In-111 platelets accumulated markedly over the abdominal aortic graft with a shortened platelet survival time and reflected changes in hematologic studies, which showed low platelet counts and a high concentration of fibrinogen degradation products in the plasma. If a strong clinical likelihood of local disseminated intravascular coagulation exists, then In-111 platelets may be valuable in localizing the focus of platelet consumption.     

Iodine-131 MIBG uptake in metastatic medullary carcinoma of the thyroid. A patient treated with somatostatin

A 47-year-old man with multiple endocrine neoplasia (MEN) type 2a syndrome in whom metaiodobenzylguanidine (MIBG) concentrated in lesions from metastatic medullary carcinoma of the thyroid is reported. A somatostatin analogue (Sandostatin SMS 201-995) alleviated the symptoms of flushing and diarrhea associated with the elevated calcitonin levels but it did not alter either the course of the disease or the MIBG images. A review of the literature is presented of the noncatecholamine secreting tumors associated with MIBG uptake. Similarities between this case and metastatic carcinoid syndrome are discussed.     

EORTC QLQ-BM22 and QLQ-C30 quality of life scores in patients with painful bone metastases of prostate cancer treated with strontium-89 radionuclide therapy

Purpose

Approximately 80?% of patients with prostate cancer will develop bone metastases, which often lead to bone pain and skeletal-related events. Sr-89 is an established alternative for the palliation of bone pain in prostate cancer. We aimed to assess the effect of Sr-89 radionuclide therapy on quality of life (QOL) in prostate cancer patients with painful bone metastases.

Materials and methods

Thirteen patients received a single intravenous injection of Sr-89 at a dose of 2.0?MBq/kg. All patients underwent QOL evaluation prior to Sr-89 treatment and 1, 2, and 3?months afterward using the Japanese version of the EORTC QLQ-BM22, EORTC QLQ-C30, a VAS, and face scale. We also evaluated PSA and ALP response and toxicity of the Sr-89 therapy.

Results

The pain characteristics subscale of the EORTC QLQ-BM22 was significantly reduced from 1?month onward compared with the baseline. The functional interference and psychosocial aspects subscales were significantly higher than baseline from 2?months onward. At 2?months, VAS indicated a significant reduction in pain as compared to the baseline. Sr-89 therapy caused a nonsignificant reduction in PSA and ALP levels. No patients had leukocyte toxicity, and one patient had grade 3 platelet toxicity.

Conclusion

Sr-89 radionuclide therapy can provide not only reduced pain characteristics but also better psychosocial aspects and functional interference in patients with painful bone metastases of prostate cancer.     

Bone pain palliation with strontium-89 in cancer patients with bone metastases.

Strontium-89 is a pure beta-emitting radioisotope, a chemical analogue of calcium, and it is therefore avidly concentrated by areas of high osteoblastic activity. Selective uptake and prolonged retention at sites of increased bone mineral turnover provide precise bone lesions targeting. 89Sr chloride (commercialised as Metastron) is typically administered in a single 150 MBq parenteral dose. Its radioactive emission poses very little radioprotection concerns. Overall, studies show pain relief in up to 80% of patients, of which 10 to 40% became effectively pain free. The mean duration of palliation was 3-4 months. The mechanism of pain relief is controversial ; it is probably, but not only, related to the absorbed dose in the tumour and bone. There is no clear dose-response relationship. The only reported toxicity is temporary myelosuppression. WBC and platelets should be monitored at least on a weekly basis until they return to baseline. It seems that only patients with a reasonably good general condition stand to benefit from this treatment. In conclusion, systemic radionuclide therapy using 89Sr represents a feasible, safe, effective, well tolerated and cost-effective palliative treatment in patients with refractory bone pain.     

89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

Purpose

Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. ⁸⁹Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection.

Methods

Ten patients with metastatic prostate cancer received 5 mCi of ⁸⁹Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by ⁸⁹Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of ⁸⁹Zr-huJ591 was done. Optimal time for imaging post-injection was determined.

Results

The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of ⁸⁹Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1–14 h) and 62 ± 13 h (range 51–89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153–317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on ⁸⁹Zr-huJ591, while the remaining 11 lesions were ⁸⁹Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on ⁸⁹Zr-huJ591 study, while the conventional imaging modality was negative.

Conclusion

⁸⁹Zr-huJ591 PET imaging of prostate-specific membrane antigen expression is safe and shows good localization of disease in prostate cancer patients. Liver is the critical organ for dosimetry, and 7 ± 1 days is the optimal imaging time. A larger study is underway to determine lesion detection in an expanded cohort of patients with metastatic prostate cancer.     

Characteristic X-ray imaging for palliative therapy using strontium-89 chloride: understanding the mechanism of nuclear medicine imaging of strontium-89 chloride

Strontium-89 (Sr-89) chloride is a targeted palliative therapy used for painful bone metastasis in which repeated doses can be administered, and its usefulness has been reported in the case of bone metastasis of various primary tumors. However, the effectiveness of the pain relief treatment is only described using a subjective index such as the visual analog scale, which lacks objectivity. Although various attempts at quantifying the effectiveness of Sr-89 chloride therapy have been reported using nuclear medicine imaging for energy peaks around 70–80 keV, the principle of Sr-89 chloride imaging has not been explained. In this study, the principle of nuclear medicine imaging for Sr-89 chloride was evaluated using a fundamental study. Additionally, the optimal collimator for acquiring Sr-89 chloride image data was evaluated. Based on the results, the principle of nuclear medicine imaging for Sr-89 chloride could be explained: the energy peaks were characteristic X-rays produced by interactions between gamma rays (514 keV) emitted from Sr-85, which is included during the manufacturing process of the Sr-89 chloride solution, and the lead collimator used in the imaging. The optimal collimator for generating characteristic X-rays efficiently was identified as a middle-to-high energy collimator.     

89Sr治疗老年患者前列腺癌骨转移骨痛的临床观察

目的 评价89^SrCl2对老年患者前列腺癌骨转移伴骨痛的临床疗效及不良反应.方法 对外科去势治疗术后的老年患者前列腺癌骨转移伴有不同程度骨痛患者48例,使用89^SrCl2静脉注射治疗,观察其镇痛效果、骨转移灶的变化、前列腺特异性抗原（PSA）及不良反应等.结果 48例患者接受89^Sr治疗后,止痛的总有效率达89.6%,无效10.4%,骨转移灶有明显减少.对PSA有不同程度的下降.所有治疗者均未发现严重的不良反应和毒副作用.结论 89^SrCl2对去势治疗术后的老年患者前列腺癌骨转移骨痛的临床止痛疗效明显,特别是对多发骨转移癌伴骨痛患者是一种有效的治疗方法.     

Iliopelvic lymphoscintigraphy as a predictor of early metastatic disease in patients with prostate carcinoma.

Fifty-one patients had iliopelvic lymphoscintigraphy (IPL) as part of the initial assessment of newly diagnosed prostate carcinoma over a 3-year period. Investigations other than IPL showed that all patients had disease confined to the prostate, and they received radiotherapy to the prostate and regional pelvic lymph nodes. Patients with complete absence of activity in an iliac chain on IPL were excluded from the analysis because that finding could have resulted from tumor replacement or a failed injection. Of the remaining 41 patients, 12 had abnormal scintigrams, and 6 (50%) had recurrence within a mean 15-month follow-up period. Of 29 patients with normal scintigrams, 26 (90%) remain disease free over an average 27-month follow-up period.     

Renal cell carcinoma in a patient successfully treated for Wilms's tumor.

A woman who had received successful therapy for Wilm's tumor of one kidney in childhood developed renal cell carcinoma in the opposite kidney 21 years later. Such an occurrence has not been reported previously. A discussion of the differential diagnosis of calcified renal mass lesions and the angiographic differentiation between Wilms's tumor and renal cell carcinoma is presented. The possible relationship between these two primary renal tumors is considered.     

Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement

This retrospective study evaluated the toxicity and efficacy of strontium-89 chloride (Metastron, Amersham) in 94 patients with painful bone metastases of prostate cancer (117 injections of 150 MBq) and compared the efficacy of treatment in patients with moderate and extensive bone involvement. The predictive value of flare response with regard to analgesic response was also studied. High-grade leukothrombopenias were observed after only 5% of injections. An improvement in quality of life was obtained in 65% of cases, a decrease in pain in 78% (31% complete response) and a reduction of analgesics in 60%. Efficacy was significantly better for pain decrease (P=0.005) and reduction of analgesics (P=0.018), and response was significantly longer (P<0.0035) in patients with moderate than in patients with extensive bone involvement. The flare response observed in 23% of cases was not predictive of pain response (P=0.919) or reduction of analgesics (P=0.353). A second dose prolonged analgesia in three-quarters of cases without any apparent increase in toxicity. These results confirm the benefit of 89Sr chloride for the treatment of metastatic bone pain and suggest that internal radiotherapy should be started earlier. A bone scan could be proposed at the time of hormonal escape resulting in bone pain, and internal radiotherapy could be initiated when several metastatic foci exist, even if only one is painful. In this way, pain-free follow-up could be prolonged, and the transition to other therapeutic approaches, particularly opioids, delayed.     

Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement

This retrospective study evaluated the toxicity and efficacy of strontium-89 chloride (Metastron, Amersham) in 94 patients with painful bone metastases of prostate cancer (117 injections of 150 MBq) and compared the efficacy of treatment in patients with moderate and extensive bone involvement. The predictive value of flare response with regard to analgesic response was also studied. High-grade leukothrombopenias were observed after only 5% of injections. An improvement in quality of life was obtained in 65% of cases, a decrease in pain in 78% (31% complete response) and a reduction of analgesics in 60%. Efficacy was significantly better for pain decrease (P=0.005) and reduction of analgesics (P=0.018), and response was significantly longer (P<0.0035) in patients with moderate than in patients with extensive bone involvement. The flare response observed in 23% of cases was not predictive of pain response (P=0.919) or reduction of analgesics (P=0.353). A second dose prolonged analgesia in three-quarters of cases without any apparent increase in toxicity. These results confirm the benefit of ⁸⁹Sr chloride for the treatment of metastatic bone pain and suggest that internal radiotherapy should be started earlier. A bone scan could be proposed at the time of hormonal escape resulting in bone pain, and internal radiotherapy could be initiated when several metastatic foci exist, even if only one is painful. In this way, pain-free follow-up could be prolonged, and the transition to other therapeutic approaches, particularly opioids, delayed.     

Decreased serum E-selectin concentration after 89Sr-chloride therapy for metastatic prostate cancer bone pain.

Palliative systemic radionuclide therapy with 89Sr-chloride is a useful intervention for patients with bone pain from metastatic prostatic cancer. Although this radionuclide is highly effective, its mechanism of action remains unresolved. This investigation sought to determine whether systemic radionuclide therapy decreases the production of cell adhesion molecules (E-selectins) that participate in the metastatic process. METHODS: Sera were collected from 25 men with metastatic (stage IV) prostate carcinoma who received 89Sr-chloride palliative therapy and from 10 age-matched healthy volunteers. The serum concentration of E-selectin was quantified by an enzyme-linked immunosorbent assay. Sera from 5 patients who received 2 courses of radionuclide therapy were also included in the analysis. RESULTS: A 2.8-fold decrease in serum E-selectin concentration occurred within 2 mo of radionuclide therapy (P < 0.0001). At 10 mo, however, the concentration increased to a mean (+/- SD) of 151.2 +/- 51.3 ng/mL, surpassing the baseline concentration. This pattern coincided with symptomatic improvement and subsequent health status deterioration. For patients who received 2 courses of radionuclide therapy, a second fall in serum E-selectin concentration followed the second radionuclide treatment. CONCLUSION: A significant decrease in serum E-selectin concentration was observed after systemic radionuclide therapy. This finding suggests that expression of cell adhesion molecules, an important determinant of metastatic progression, may be inhibited by 89Sr-chloride.     

Resolved splenic accumulation of Tc-99m HMDP after recovery of disseminated intravascular coagulation in a patient with rhabdomyosarcoma.

Unusual, intense splenic radioactivity was seen on bone scintigraphy with Tc-99m HMDP in a 14-year-old boy with alveolar rhabdomyosarcoma complicated by disseminated intravascular coagulation. Abnormal splenic radioactivity was resolved after recovery from the disseminated intravascular coagulation. During treatment of disseminated intravascular coagulation and tumors, the patient received repeated blood transfusions, resulting in iron overload, but this did not prevent the abnormal splenic uptake from resolving. This case indicates that disseminated intravascular coagulation may be a cause of splenic accumulation of bone-seeking agents, and that abnormal splenic uptake can be resolved.     

Comparison of strontium-89 solution sources in UK hospitals, 2003.

Concerns have been raised within the nuclear medicine field about the accuracy of measurements of 89Sr. The 85Sr impurity present in the 89Sr solution has a significant effect on the response of radionuclide calibrators used in hospitals. A comparison was conducted between the National Physical Laboratory (NPL) and the UK hospital physics community. Only 58% of the results were within 5% of the NPL value. Work at NPL has resulted in correction factors for the NPL secondary standard radionuclide calibrator and for Capintec calibrators, which will produce a significant improvement in performance.