Evaluation of bone metastatic burden by bone SPECT/CT in metastatic prostate cancer patients: defining threshold value for total bone uptake and assessment in radium-223 treated patients

Objectives

To establish a new three-dimensional quantitative evaluation method for bone metastasis, we applied bone single photon emission tomography with computed tomography (SPECT/CT). The total bone uptake (TBU), which measures active bone metastatic burden, was calculated as the sum of [mean uptake obtained as standardized uptake value (SUV) above a cut-off level]?×?(the volume of the lesion) in the trunk using bone SPECT/CT. We studied the threshold value and utility of TBU in prostate cancer patients treated with radium-223 (Ra-223) therapy.

Methods

To establish the threshold value of TBU, we compared bone metastatic and non-metastatic regions in 61 prostate cancer patients with bone metastasis and 69 without. Five fixed sites in each patient were selected as evaluation points and divided into bone metastatic and non-metastatic sites. Sensitivity and specificity analysis was applied to establish the threshold level. Using the obtained threshold value, we then calculated the TBU in nine prostate cancer patients who received Ra-223 therapy, and compared the results with the bone scan index (BSI) by BONENAVI^® and visual evaluation of bone scintigraphy.

Results

Uptake was significantly lower in non-metastatic sites in patients with bone metastasis than in patients without metastasis. Sensitivity and specificity analysis revealed SUV?=?7.0 as the threshold level. There was a discrepancy between TBU and BSI change in two of the nine patients, in whom TBU change correlated with visual judgement, but BSI change did not. In two patients, BSI was nearly 0 throughout the course, but the TBU was positive and changed, although the change was not large. These results suggest that TBU may be more accurate and sensitive than BSI for quantitative evaluation of active bone metastatic burden.

Conclusion

We established a threshold value (SUV?>?7.0) for three-dimensional TBU for evaluating active bone metastatic burden in prostate cancer patients using bone SPECT/CT. Despite the small number of patients, we expect the change in TBU could be more accurate and sensitive than the change in BSI among patients who received Ra-223.

     

Impact of treatment delay in Radium-223 therapy of metastatic castration-resistant prostate cancer patients

Background

Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities. The aim of this study was to assess whether prolonged interval between Ra-223 cycles to non-disease related causes had a negative impact on clinical outcome of therapy.

Materials and methods

Retrospective single-center study of mCRPC patients who initiated Ra-223 therapy in the period from March 2014 to February 2015. End points were number of completed Ra-223 cycles, overall survival (OS) and radiographic progression-free survival (rPFS). Bone scintigraphy, CT of thorax and abdomen, hematological status, PSA and alkaline phosphatase were evaluated prior to first dose and after 3rd and 6th treatment, respectively. Follow-up period was 18 months after first Ra-223 cycle.

Results

A total of 50 consecutive patients initiated Ra-223 therapy in the time period. Seventeen of 50 patients (34%) had prolonged interval between cycles due to delivery problems. Median delay was 4 weeks (range 3–9 weeks). Patients with delayed treatment had significantly longer median rPFS [delayed patients: 7.1 months (95% CI 4.9–9.3) vs. 4.5 months (95% CI 2.8–6.3)]. There was no significant difference in number of completed cycles or median OS.

Conclusion

We find no negative impact of prolonged interval between Ra-223 cycles due to non-disease related reasons on OS, rPFS or number of completed treatment cycles.

     

Introduction of the targeted alpha therapy (with Radium-223) into clinical practice in Japan: learnings and implementation

Annals of Nuclear Medicine - Radium-223 dichloride (Ra-223) is the first targeted alpha therapy approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with bone...     

Changes in Skeletal Tumor Activity on 18F-choline PET/CT in Patients Receiving 223Radium Radionuclide Therapy for Metastatic Prostate Cancer

Radium-223 dichloride is an alpha-emitting radiopharmaceutical shown to prolong survival in patients with castrate-resistant prostate cancer (CRPC) and symptomatic skeletal metastases. This report describes in two patients the acute changes in bone metastatic activity detected by F-18 choline PET/CT imaging midway during treatment with radium-223 dichloride. In addition to visual and standardized uptake value analysis, changes in the whole-body tumor burden were quantified by measuring the difference in net metabolically active tumor volume (MATV) and total lesion activity (TLA) between pre- and mid-treatment PET scans. After the third dose of radium-223 dichloride, near-total disappearance of abnormal skeletal activity was observed in one case (net MATV change from 260.7 to 0.8 cc; net TLA change from 510.7 to 2.1), while a heterogeneous tumor response was observed in the other (net MATV change from 272.2 to 241.3 cc; net TLA change from 987.1 to 779.4). Corresponding normalization and persistent elevation in serum alkaline phosphatase levels were observed in these cases, respectively. Further research is needed to determine the predictive value of serial F-18 choline PET/CT imaging in patients receiving radium-223 dichloride for CRPC.     

Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters

Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer. Different radionuclides that emit β-rays such as ¹⁵³Samarium and ⁸⁹Strontium and achieve palliation are commercially available. In contrast to β-emitters, ²²³Radium as a α-emitter has a short path-length. The advantage of the α-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms. Due to the limited range of the α-particles the bone surface to red bone marrow dose ratio is also lower for ²²³Radium which is expressed in a lower myelotoxicity. The α emitter ²²³Radium dichloride is the first radiopharmaceutical that significantly prolongs life in castrate resistant prostate cancer patients with wide-spread bone metastatic disease. In a phase III, randomized, double-blind, placebo-controlled study 921 patients with castration-resistant prostate cancer and bone metastases were randomly assigned. The analysis confirmed the ²²³Radium survival benefit compared to the placebo (median, 14.9 mo vs 11.3 mo; P < 0.001). In addition, the treatment results in pain palliation and thus, improved quality of life and a delay of skeletal related events. At the same time the toxicity profile of ²²³Radium was favourable. Since May 2013, ²²³Radium dichloride (Xofigo^®) is approved by the US Food and Drug Administration.     

Epithelioid Hemangioendothelioma of the Foot

We describe the case of an 18-year-old male Army reservist presenting with left lower extremity pain for which he was initially diagnosed with a stress injury. After failing conservative treatment, a radiograph was obtained showing a “lacelike” appearance of the medullary bone in the foot and ankle. Magnetic resonance imaging subsequently demonstrated widespread polyostotic marrow replacement with coarsened trabeculations. A biopsy was obtained which diagnosed the patient with polyostotic epithelioid hemangioendothelioma which is the most common malignant vascular tumor of bone. The patient ultimately underwent a below the knee amputation once computed tomography of the chest, abdomen, and pelvis excluded distant metastatic disease. It is important for radiologists to be aware of this diagnosis because osseous epithelioid hemangioendothelioma can present like a stress injury and be mistaken for a less serious diagnosis while potentially having visceral involvement.     

Validation of the 3-variable prognostic score (3-PS) in mCRPC patients treated with 223Radium-dichloride: a national multicenter study

Annals of Nuclear Medicine - Radium-223 (223Ra) has been approved for treatment in patients with metastatic castration-resistant prostatic cancer (mCRPC) and bone metastasis. This α-emitting...     

Treatment of Bone Metastasis with Bone-Targeting Radiopharmaceuticals

Bone is a common metastatic site of cancer. Bone metastasis reduces life expectancy and results in serious symptoms and complications such as bone pain, pathological fractures, and spinal cord compression, decreasing quality of life by restricting sleep and mobility. Treatment for bone metastasis includes drugs (pure analgesics, hormones, cytotoxic chemotherapy, and bisphosphonates, among others), external radiation therapy, surgery, and radionuclide therapy using bone-targeting radiopharmaceuticals. Particulate radiation with α- or β-rays is used as a bone-targeting radiopharmaceutical in radionuclide therapy. β-Emitters have lower energy and a longer range than α-emitters and have less tumoricidal activity and deliver more radiation to adjacent normal tissue. Therefore, the main therapeutic effect of bone-targeting β-emitters such as ⁸⁹Sr-dichloride is bone pain palliation rather than enhanced survival. In contrast, α-emitters such as ²²³Ra-dichloride have high energy and a short range, resulting in greater tumoricidal activity and less radiation damage to adjacent normal tissue. Treatment with bone-targeting α-emitters can improve survival and decrease bone pain. This review focuses on the principles and clinical utility of several clinically available bone-targeting radiopharmaceuticals in metastatic bone disease.     

Radium-223 dichloride in clinical practice: a review

The onset of skeletal metastases is typical of advanced-stage prostate cancer and requires a multidisciplinary approach to alleviate bone pain and try to delay disease progression. The current therapeutic armamentarium includes conventional analgesics, chemotherapeutic agents, immunotherapy, androgen-deprivation therapy, osteoclast inhibitors (bisphosphonates, denosumab), surgical interventions, external-beam radiotherapy and radionuclide metabolic therapy. Many studies in recent decades have demonstrated the efficacy of various radiopharmaceuticals, including strontium-89 and samarium-153, for palliation of pain from diffuse skeletal metastases, but no significant benefit in terms of disease progression and overall survival has been shown. The therapeutic landscape of metastatic skeletal cancer significantly changed after the introduction of radium-223, the first bone-homing radiopharmaceutical with disease-modifying properties. In this paper we extensively review the literature on the use of radium-223 dichloride in metastatic castration-resistant prostate cancer.     

Whole-Body Bone Scan Findings after High-Intensity Focused Ultrasound (HIFU) Treatment

Purpose

This study aims to examine the findings of ^99mTc-diphosphonate bone scans in cancer patients with a history of HIFU treatment.

Methods

Bone scan images of patients with a history of HIFU treatment for primary or metastatic cancer from January 2006 to July 2010 were retrospectively reviewed. Cases of primary bone tumor or HIFU treatment reaching only the superficial soft tissue layer were excluded.

Results

Bone scan images of 62 patients (26 female, 36 male; mean age 57 ± 9 years) were studied. HIFU treatment was performed in the liver (n = 40), pancreas (n = 16), and breast (n = 6). Mean interval time between HIFU treatment and bone scan was 106 ± 105 days (range: 1–572 days). Of 62 scans, 43 showed diffusely decreased uptake of bone within the path of HIFU treatment: antero-axillary and/or posterior arcs of right 5th to 11th ribs in 34 cases after treatment of hepatic lesions; anterior arcs of 2nd to 5th ribs in 5 cases after treatment for breast tumors; and posterior arcs of left 9th to 11th ribs or thoraco-lumbar vertebrae in 4 cases after treatment for pancreas tumor. Of 20 patients who had bone scans more than twice, five showed recovered uptake of the radiotracer in the involved ribs in the follow-up bone scan.

Conclusion

Of 62 bone scans in patients with a history of HIFU treatment for primary or metastatic cancer, 69% presented diffusely decreased uptake in the bone in the path of HIFU treatment.     

A novel tool for improving the interpretation of isotope bone scans in metastatic prostate cancer

Objectives:The isotope bone scan (IBS) is the gold-standard imaging modality for detecting skeletal metastases as part of prostate cancer staging. However, its clinical utility for assessing skeletal metastatic burden is limited due to the need for subjective interpretation. We designed and tested a novel custom software tool, the Metastatic Bone Scan Tool (MetsBST), aimed at improving interpretation of IBSs, and compared its performance with that of an established software programme.Methods:We used IBS images from 62 patients diagnosed with prostate cancer and suspected bone metastases to design and implement MetsBST in MATLAB by defining thresholds used to identify the texture and size of metastatic bone lesions. The results of MetsBST were compared with those of the commercially available automated Bone Scan Index (aBSI) with regression analysis.Results:There was strong agreement between the MetsBST and aBSI results (R² = 0.9189). In a subregional analysis, MetsBST quantified the extent of metastatic disease in multiple bone sites in patients receiving multimodality therapy (radium-223 and external beam radiotherapy) to illustrate the differences in bone metastatic response to different treatments.Conclusion:The results of MetsBST and the commercial software aBSI were highly consistent. MetsBST introduces novel clinical utility by its ability to differentiate between the responses of different bone metastases to multimodality therapies.Advances in knowledge:MetsBST reduces the variability in assessment of tumour burden caused by subjective interpretation. Therefore, it is a useful aid to physicians reporting nuclear medicine scans, and may improve decision-making in the treatment of metastatic prostate cancer.     

Metastatic choriocarcinoma with hemorrhagic complications and spontaneous ovarian hyperstimulation syndrome: A case report

Gestational choriocarcinoma is a malignant trophoblastic tumor arising from any gestational event, even with a long latency period, generally in the reproductive female. It is associated with a high level of beta-human chorionic gonadotropin. Its primary site is usually the uterus but not all patients have a detectable lesion in this site. Regression of the primary tumor after it has metastasized is not uncommon, and one-third of cases manifest as complications of metastatic disease. In this report we present an uncommon case of gestational choriocarcinoma with lung, liver and jejunal metastases at the time of diagnosis without evidence of pelvic disease, in 34-year-old woman. The main points of interest of our case were the development of the ovarian hyperstimulation syndrome with massive multicystic ovarian enlargement induced by high level of beta-human chorionic gonadotropin and the bleeding of jejunal and liver metastases, due to the high vascularity of the tumor tissue, a condition known as “Choriocarcinoma Syndrome”. We will focus on the radiological findings of metastases, bleeding complications and ovarian hyperstimulation syndrome.     

Improved Detection of Lung or Bone Metastases with an I-131 Whole Body Scan on the 7th Day After High-Dose I-131 Therapy in Patients with Thyroid Cancer

Purpose

The purpose of this study is to compare post-therapy third day and seventh day I-131 whole body scans (3DWBS and 7DWBS) in detecting lung or bone metastasis from well-differentiated thyroid cancer.

Materials and Methods

We enrolled 52 patients with lung or bone metastasis out of 1,152 patients who were treated with high-dose I-131 therapy from January 2008 to June 2009. All patients underwent 3DWBS and 7DWBS. I-131 avidity was classified into three grades: no uptake, suspicious for uptake, and definite uptake. We compared the presence and grades of metastatic lesions on each scan. We categorized all cases into three groups based on I-131 uptake on each scan and compared several clinical parameters including FDG uptake and thyroglobulin (Tg) level among the groups.

Results

Sixty metastatic cases from 52 patients (45 lung and 15 bone metastases) were included. In 35 cases, I-131-avid metastatic lesions were detected by both 3DWBS and 7DWBS (group A). In 15 cases, metastatic lesions were missed on 3DWBS but detected on 7DWBS (group B). In 10 cases, I-131 uptake was not detected on either 3DWBS or 7DWBS (group C). Ten of 45 cases (22.2%) of lung metastasis that were negative on 3DWBS were detected on 7DWBS (p = 0.002). Five of 15 cases (33.3%) of bone metastasis that were negative on 3DWBS were detected on 7DWBS (p = 0.0625). The serum Tg level (TSH stimulated) was significantly different among groups A, B, and C (p = 0.0030). However, after exclusion of cases without a history of I-131 therapy, there was no significant difference in serum Tg level among the groups (p = 0.2330). The number of cases with a prior history of metastasis was higher in group A than in group B (p = 0.0069). However, there was no significant difference in prior history of metastasis between groups A and C (p = 0.8107).

Conclusion

7DWBS showed more lung or bone metastatic lesions than 3DWBS. After high-dose I-131 therapy, 7DWBS should be considered regardless of the results of the 3DWBS for the diagnosis of lung or bone metastasis from well-differentiated thyroid cancer.     

Evaluation of procedures for determination of Ra-226 in water by α-particle spectrometry with emphasis on the recovery

Radium-226 is one of the best known long-lived α-emitters abundantly present in the environment. The determination of radium isotopes in environmental samples usually requires a demanding chemical separation before measurement and quantification. Each step in the chemical separation process can involve losses of the analyte, therefore it is of vital importance that the recovery of the whole radiochemical procedure is evaluated. The emphasis of the work presented was determination of the chemical recovery using the different yield tracers Ra-223, Ra-225 and Ba-133.     

Reversibility of castration resistance status after Radium-223 dichloride treatment: clinical evidence and review of the literature

Abstract

In the history of prostate cancer, some of the patients progressed to castration-resistant prostate cancer (CRPC) stage and, although new drugs and treatment protocols have been introduced, CRPC presents poor prognosis. This review is focused on biological mechanisms, underlying CRPC described in scientific literature in order to explain the reversion of resistance to castration. We present the case of a 73-year-old man, affected by bone metastatic CRPC, early treated with Radium-223 with a complete response. After 15 months from Radium-223 treatment, prostate-specific antigen increased with radiological progression. Androgen deprivation therapy was again performed and was effective, despite previous CRPC condition and no known mechanisms that may explain the reversion of this condition. Therefore, to our knowledge, he is the unique described case of the reversion of resistance to castration. Nevertheless, promising aspects may be lack of intrametastatic production of androgen or the suppression of bypass androgen receptor signaling pathways. Furthermore, the cytotoxic action of Radium-223 on cancer stem cell (CSC), due to surrounding clones with high-bone turnover, or the immune response that underlying the abscopal effect, may also modulate the reversion of CRPC after Radium-223. If confirmed by multicenter trials, the reversion of CRPC may impact on the management of prostate cancer.     

The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis

Tumour heterogeneity has, in recent times, come to play a vital role in how we understand and treat cancers; however, the clinical translation of this has lagged behind advances in research. Although significant advancements in oncological management have been made, personalized care remains an elusive goal. Inter- and intratumour heterogeneity, particularly in the clinical setting, has been difficult to quantify and therefore to treat. The histological quantification of heterogeneity of tumours can be a logistical and clinical challenge. The ability to examine not just the whole tumour but also all the molecular variations of metastatic disease in a patient is obviously difficult with current histological techniques. Advances in imaging techniques and novel applications, alongside our understanding of tumour heterogeneity, have opened up a plethora of non-invasive biomarker potential to examine tumours, their heterogeneity and the clinical translation. This review will focus on how various imaging methods that allow for quantification of metastatic tumour heterogeneity, along with the potential of developing imaging, integrated with other in vitro diagnostic approaches such as genomics and exosome analyses, have the potential role as a non-invasive biomarker for guiding the treatment algorithm.Although continual improvements in diagnosis, surgical techniques and radiation oncology have together provided improved survival for many forms of human cancers, a majority of deaths from cancer are caused by the development and continuous growth of metastases that are resistant to conventional therapies. Similarly, although the use of systemic non-targeted and targeted adjuvant therapies has helped to prevent the spread of tumour cells from the primary site and is now a standard practice for many tumour types, the emergence of resistant disease continues to be a significant cause of patient mortality. These features provide an insight into the dynamic nature of the signalling network within the tumour cells,¹ and human cancers are now being increasingly recognized as heterogeneous, characterized by distinct pathological, genomic, clinical and therapeutic features.Nearly 150 years after the original theory of tumours originating from immature cells by Virchow,² innovative technological approaches unequivocally demonstrate the cellular heterogeneity of tumours, composed of distinct subpopulations of cancer cells within (“intra”) and between (“inter”) tumours of individual patients. These subpopulations are characterized by specific genetic and morphological profiles, representing the clonal selection and evolution of that tumour.^3,4 This heterogeneity provides a powerful internal mechanism through which tumour cells can ultimately escape environmental stresses, including oncological therapies, posing a considerable challenge for translational researchers.There is considerable evidence that the tumour microenvironment actively contributes to tumour heterogeneity.⁵ Arguably the best example of this is the “pre-metastatic niche”, defined as the creation of an ideal thriving environment for the primary tumour to “seed” to. Through the secretion of cytokines, chemokines and growth factors, the primary tumour “primes” a distal site to become an ideal niche/target organ, favourable for future metastatic colonization.⁶ Although in some cases the target organ is already primed for metastatic spread and many organs may have “seeding” of cells, only a few will take “root”.⁷ Increasing understanding of tumour heterogeneity demands an effort from researchers to establish and understand pre-metastatic changes within distant organs and their major drivers.This new paradigm of cancer heterogeneity has yet to be fully assimilated into everyday patient management. It has been well documented with certain cancers that imaging signals can show phenotypic tumour heterogeneity and have clinical implications; for example, in radio-iodine imaging of metastatic thyroid cancer, some metastatic lesions may not take up radio-iodine and therefore will be unaffected by radio-iodine therapy. However, for the majority of tumours, biopsies remain the standard of care for assessing tumour biology but cannot be expected to represent the entirety of a tumour in this tumour heterogenic era.⁴ Many physicians advocate the re-biopsy of metastatic disease at re-presentation for histological analysis and comparison with the primary, in an attempt to improve the choice of therapy upon relapse, having taken into account, for instance, intertumoral heterogeneity between the primary and metastatic disease.⁸ Repeated biopsy of tumour tissue is invasive, may be practically difficult, has resource implications and is clearly confounded by intratumoral heterogeneity. These shortcomings give huge potential to the recent advances in molecular imaging, which have the ability to visualize and quantify heterogeneity of tumour receptor expression, metabolism, apoptosis, blood flow or structure, non-invasively over time, i.e. at baseline and to assess response to treatment.Owing to space constraints, we can only select a subset of imaging techniques for illustration purposes; a more comprehensive précis of the different image modalities has been reviewed elsewhere.⁸     

Radioimmunodetection and therapy of breast cancer

Breast cancer is the second most-common cause of cancer death in women in the United States. Although more than 60% of patients can now be cured by initial treatment, the rest, although perhaps receiving palliation with currently available therapy, will die of their disease. Early detection of micrometastasis and improved treatment strategies are needed. Monoclonal antibody (mAb)-based imaging and tumor targeted therapy holds the potential to impact these problems. The most significant results of systemically administered antibody-based radiopharmaceuticals for detection and targeted therapy (radioimmunotherapy [RIT]) of breast cancer give strong evidence that this potential can be realized. Interest in immunoimaging recently has focused on small mAb modules used with 18F, 64Cu, or 124I to detect minimal disease in breast cancer by positron emission tomography or single-photon emission computed tomography. Reported therapy trials in advanced breast cancer have yielded objective responses and minimal toxicity. These studies have spanned several radionuclides as well as several mAb, fragments and approaches, including dose intensification with bone marrow support; combined therapy with other modalities (ie, CM-RIT); biodegradable peptide linkers; and pretargeting. RIT evaluated in clinical breast cancer trials has delivered as much as 4000 cGy to metastatic breast cancer per therapy dose with marrow stem cell support. Preclinical studies have demonstrated further promising strategies for breast cancer. RIT studies must address the key issue: enhancing the therapeutic index (tumor effect verses most sensitive normal tissue (bone marrow) effect). Approaches now include newly engineered mAb, scFv modular constructs, blood clearance on demand, enhanced pretargeting, applications of both alpha and beta emitting radionuclides, and combination therapy using molecular triggers for therapeutic synergy. These strategies for detection and treatment of metastatic breast cancer should lead to notable clinical impact on management and cure of breast cancer.     

A theoretical model for the production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation on a small scale by bombarding Ra-226 with high-energy photons from a medical linear accelerator (linac) to produce Ra-225, which subsequently decays to Ac-225, which can be used as a generator to produce Bi-213 for use in 'targeted alpha therapy' for cancer. This paper examines the possibility of producing Ac-225 with a linac using an accurate theoretical model in which the bremsstrahlung photon spectrum at 18 MV linac electron energy is convoluted with the corresponding photonuclear cross sections of Ra-226. The total integrated yield can then be obtained and is compared with a computer simulation. This study shows that at 18 MV, the photonuclear reaction on Ra-226 can produce low activities of Ac-225 with a linac. However, a high power linac with high current, pulse length and frequency is needed to produce practical amounts of Ac-225 and a useful reduction of Ra-226.     

Enhanced uptake of 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone treatment: potential for increasing delivery of therapeutic agents.

Following androgen ablation therapy, skeletal metastases from prostate cancer appear in some instances to show an increase in 99Tcm-methylene diphosphonate (99Tcm-MDP) uptake. Such a phenomenon could represent a mechanism to increase delivery of bone-seeking therapeutic agents to skeletal metastatic sites. The aim of this study was to characterize more precisely the potential increase in 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone therapy. Baseline bone scans were performed within 1 week of onset of hormone therapy in patients with stage D2 prostate cancer followed by multiple repeat bone scans for up to 4-6 weeks. The count density within metastatic lesions was divided by the average count density from several areas of normal bone to obtain a lesion to normal bone uptake ratio (L/N) for each lesion in each scan. Altogether, 61 skeletal metastases were identified on bone scans from five subjects. Eighty-four percent (51/61) of these lesions showed an increase in 99Tcm-MDP activity relative to normal bone following initiation of hormone therapy with a mean peak increase of 39%. Thirty-nine of these 51 metastatic lesions showed maximum uptake at 3 weeks post-onset of hormone treatment. From our findings, it appears that approximately 3 weeks following initiation of hormone blockade, most skeletal metastases from prostate cancer will demonstrate significantly enhanced 99Tcm uptake relative to normal bone. Consequently, it may be possible to improve the uptake and effectiveness of therapeutic bone-seeking radiopharmaceuticals by administering these agents following hormone therapy in patients with prostate cancer metastases.     

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.