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1.
Curr Med Chem ; 27(19): 3187-3249, 2020.
Article in English | MEDLINE | ID: mdl-30714520

ABSTRACT

Bone pain arising from secondary skeletal malignancy constitutes one of the most common types of chronic pain among patients with cancer which can lead to rapid deterioration of the quality of life. Radionuclide therapy using bone-seeking radiopharmaceuticals based on the concept of localization of the agent at bone metastases sites to deliver focal cytotoxic levels of radiation emerged as an effective treatment modality for the palliation of symptomatic bone metastases. Bone-seeking radiopharmaceuticals not only provide palliative benefit but also improve clinical outcomes in terms of overall and progression-free survival. There is a steadily expanding list of therapeutic radionuclides which are used or can potentially be used in either ionic form or in combination with carrier molecules for the management of bone metastases. This article offers a narrative review of the armamentarium of bone-targeting radiopharmaceuticals based on currently approved investigational and potentially useful radionuclides and examines their efficacy for the treatment of painful skeletal metastases. In addition, the article also highlights the processes, opportunities, and challenges involved in the development of bone-seeking radiopharmaceuticals. Radium-223 is the first agent in this class to show an overall survival advantage in Castration-Resistant Prostate Cancer (CRPC) patients with bone metastases. This review summarizes recent advances, current clinical practice using radiopharmaceuticals for bone pain palliation, and the expected future prospects in this field.


Subject(s)
Bone Neoplasms , Quality of Life , Bone Neoplasms/radiotherapy , Bone Neoplasms/secondary , Humans , Male , Pain , Radiopharmaceuticals
2.
Nucl Med Biol ; 43(11): 692-720, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27589333

ABSTRACT

Because of the broad incidence, morbidity and mortality associated with prostate-derived cancer, the development of more effective new technologies continues to be an important goal for the accurate detection and treatment of localized prostate cancer, lymphatic involvement and metastases. Prostate-specific membrane antigen (PSMA; Glycoprotein II) is expressed in high levels on prostate-derived cells and is an important target for visualization and treatment of prostate cancer. Radiolabeled peptide targeting technologies have rapidly evolved over the last decade and have focused on the successful development of radiolabeled small molecules that act as inhibitors to the binding of the N-acetyl-l-aspartyl-l-glutamate (NAAG) substrate to the PSMA molecule. A number of radiolabeled PSMA inhibitors have been described in the literature and labeled with SPECT, PET and therapeutic radionuclides. Clinical studies with these agents have demonstrated the improved potential of PSMA-targeted PET imaging agents to detect metastatic prostate cancer in comparison with conventional imaging technologies. Although many of these agents have been evaluated in humans, by far the most extensive clinical literature has described use of the 68Ga and 177Lu agents. This review describes the design and development of these agents, with a focus on the broad clinical introduction of PSMA targeting motifs labeled with 68Ga for PET-CT imaging and 177Lu for therapy. In particular, because of availability from the long-lived 68Ge (T1/2=270days)/68Ga (T1/2=68min) generator system and increasing availability of PET-CT, the 68Ga-labeled PSMA targeted agent is receiving widespread interest and is one of the fastest growing radiopharmaceuticals for PET-CT imaging.


Subject(s)
Antigens, Surface/metabolism , Diagnostic Imaging/methods , Enzyme Inhibitors/therapeutic use , Glutamate Carboxypeptidase II/antagonists & inhibitors , Glutamate Carboxypeptidase II/metabolism , Molecular Targeted Therapy/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Humans , Male , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology
4.
Nucl Med Mol Imaging ; 49(2): 85-107, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26085854

ABSTRACT

BACKGROUND: This review provides a comprehensive summary of the production of (177)Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of (177)Lu having the required quality for preparation of a variety of (177)Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of (177)Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. METHODS: While both "direct" and "indirect" reactor production routes offer the possibility for sustainable (177)Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. RESULTS: This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. CONCLUSION: A broad understanding and discussion of the issues associated with (177)Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of (177)Lu-labeled radiopharmaceuticals, but also help future developments.

5.
Curr Radiopharm ; 8(2): 107-18, 2015.
Article in English | MEDLINE | ID: mdl-25771377

ABSTRACT

This article presents a concise review of the production of no-carrier-added (NCA) (177)Lu by the 'indirect' route by irradiating ytterbium-176 ((176)Yb)-enriched targets. The success of this production method depends on the ability to separate the microscopic amounts of NCA (177)Lu from bulk irradiated ytterbium targets. The presence of Yb(+3) from the target in the final processed (177)Lu will adversely affect the quality of (177)Lu by decreasing the specific activity and competing with Lu(+3) complexation since ytterbium will follow the same coordination chemistry. Ytterbium and lutetium are adjacent members of the lanthanide family with very similar chemical properties which makes the separation of one from the other a challenging task. This review provides a summary of the methods developed for the separation and purification of NCA (177)Lu from neutron irradiated (176)Yb-enriched targets, a critical assessment of recent developments and a discussion of the current status of this (177)Lu production method.


Subject(s)
Lutetium/chemistry , Radioisotopes/chemistry , Ytterbium/chemistry , Isotopes/chemistry , Neutrons
6.
Curr Radiopharm ; 8(2): 78-85, 2015.
Article in English | MEDLINE | ID: mdl-25771380

ABSTRACT

Lutetium-177 ((177)Lu) is a late entrant into the nuclear medicine therapy arena but is expected to become one of the most widely used therapeutic radionuclides. This paper analyses the reason for the increasing preference of (177)Lu as a therapeutic radionuclide. While the radionuclidic properties favor its use for several therapeutic applications, the potential for large scale production of (177)Lu is also an important aspect for its acceptability as a therapeutic radionuclide. This introductory discussion also summarizes some developing clinical uses and suggested future directions for applications of (177)Lu.


Subject(s)
Lutetium/therapeutic use , Nuclear Medicine/methods , Radioisotopes/therapeutic use , Drug Design , Humans
8.
Cancer Biother Radiopharm ; 30(2): 47-71, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25710506

ABSTRACT

Peptide receptor radionuclide therapy (PRRT) is a site-directed targeted therapeutic strategy that specifically uses radiolabeled peptides as biological targeting vectors designed to deliver cytotoxic levels of radiation dose to cancer cells, which overexpress specific receptors. Interest in PRRT has steadily grown because of the advantages of targeting cellular receptors in vivo with high sensitivity as well as specificity and treatment at the molecular level. Recent advances in molecular biology have not only stimulated advances in PRRT in a sustainable manner but have also pushed the field significantly forward to several unexplored possibilities. Recent decades have witnessed unprecedented endeavors for developing radiolabeled receptor-binding somatostatin analogs for the treatment of neuroendocrine tumors, which have played an important role in the evolution of PRRT and paved the way for the development of other receptor-targeting peptides. Several peptides targeting a variety of receptors have been identified, demonstrating their potential to catalyze breakthroughs in PRRT. In this review, the authors discuss several of these peptides and their analogs with regard to their applications and potential in radionuclide therapy. The advancement in the availability of combinatorial peptide libraries for peptide designing and screening provides the capability of regulating immunogenicity and chemical manipulability. Moreover, the availability of a wide range of bifunctional chelating agents opens up the scope of convenient radiolabeling. For these reasons, it would be possible to envision a future where the scope of PRRT can be tailored for patient-specific application. While PRRT lies at the interface between many disciplines, this technology is inextricably linked to the availability of the therapeutic radionuclides of required quality and activity levels and hence their production is also reviewed.


Subject(s)
Neoplasms/radiotherapy , Radioisotopes/pharmacology , Radioisotopes/therapeutic use , Radiopharmaceuticals/pharmacology , Radiopharmaceuticals/therapeutic use , Receptors, Peptide/administration & dosage , Animals , Humans
9.
J Nucl Med ; 56(1): 159-61, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25537991

ABSTRACT

This paper discusses the benefits of obtaining (99m)Tc from non-fission reactor-produced low-specific-activity (99)Mo. This scenario is based on establishing a diversified chain of facilities for the distribution of (99m)Tc separated from reactor-produced (99)Mo by (n,γ) activation of natural or enriched Mo. Such facilities have expected lower investments than required for the proposed chain of cyclotrons for the production of (99m)Tc. Facilities can receive and process reactor-irradiated Mo targets then used for extraction of (99m)Tc over a period of 2 wk, with 3 extractions on the same day. Estimates suggest that a center receiving 1.85 TBq (50 Ci) of (99)Mo once every 4 d can provide 1.48-3.33 TBq (40-90 Ci) of (99m)Tc daily. This model can use research reactors operating in the United States to supply current (99)Mo needs by applying natural (nat)Mo targets. (99)Mo production capacity can be enhanced by using (98)Mo-enriched targets. The proposed model reduces the loss of (99)Mo by decay and avoids proliferation as well as waste management issues associated with fission-produced (99)Mo.


Subject(s)
Molybdenum/isolation & purification , Radiochemistry/instrumentation , Radionuclide Generators/instrumentation , Technetium/isolation & purification , Technetium/supply & distribution , Cyclotrons , Investments , Molybdenum/chemistry , Radiochemistry/economics , Radionuclide Generators/economics , Technetium/chemistry
11.
J Nucl Med ; 52(11): 1721-6, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21976530

ABSTRACT

UNLABELLED: This retrospective study compared the effects of single and multiple administrations of (186)Re-hydroxyethylidenediphosphonate ((186)Re-HEDP) on palliation and survival of prostate cancer patients presenting with more than 5 skeletal metastases. METHODS: A total of 60 patients were divided into 3 groups. Group A (n = 19) consisted of patients who had received a single injection; group B (n = 19), patients who had 2 injections; and group C (n = 22), patients who had 3 or more successive injections. The (188)Re-HEDP was prepared using non-carrier-added (188)Re obtained from an in-house (188)W/(188)Re generator after dilution with carrier perrhenate. Patients' data available from the referring physicians-including prostate-specific antigen levels-were entered into a Windows-based matrix and analyzed using a statistical program. The Gleason scores were similar for all 3 groups. RESULTS: Mean survival from the start of treatment was 4.50 ± 0.81 mo (95% confidence interval [CI], 2.92-6.08) for group A, 9.98 ± 2.21 mo (95% CI, 5.65-14.31) for group B, and 15.66 ± 3.23 (95% CI, 9.33-22.0) for group C. Although the 3 groups did not differ in Gleason score, the number of lost life-years was significantly lower in group C than in groups A and B. Pain palliation was achieved in 89.5% of group A, 94.7% of group B, and 90.9% of group C. CONCLUSION: Posttreatment overall survival could be improved from 4.50 to 15.66 mo by multiple-injection bone-targeted therapy with (188)Re-HEDP, when compared with a single injection. Significant pain palliation was common and independent of administration frequency.


Subject(s)
Bone Neoplasms/secondary , Bone Neoplasms/therapy , Drug Resistance, Neoplasm/radiation effects , Etidronic Acid/therapeutic use , Hormones/pharmacology , Organometallic Compounds/therapeutic use , Palliative Care/methods , Prostatic Neoplasms/pathology , Aged , Bone Neoplasms/drug therapy , Bone Neoplasms/radiotherapy , Etidronic Acid/administration & dosage , Follow-Up Studies , Hormones/therapeutic use , Humans , Male , Middle Aged , Organometallic Compounds/administration & dosage , Retrospective Studies , Survival Analysis
12.
Coron Artery Dis ; 17(4): 371-7, 2006 May.
Article in English | MEDLINE | ID: mdl-16707961

ABSTRACT

BACKGROUND: In cases of in-stent restenosis, intracoronary radiotherapy with beta-emitters and gamma-emitters has been shown to reduce the risk of repeat restenosis. The present randomised, placebo-controlled study addresses the question of whether intracoronary radiotherapy applied by the easy-to-handle Rhenium liquid-filled angioplasty balloon system is also able to reduce the angiographic re-restenosis rate in stents. METHODS AND RESULTS: At our center, from May 2000 to December 2003, 165 patients (mean age 64+/-10, median 65 years; 127 men, 38 women) with symptomatic in-stent restenosis underwent either intracoronary brachytherapy or sham procedure. Index clinical and angiographic parameters were largely comparable in both groups. Radiation therapy was performed with a standard percutaneous transluminal coronary angioplasty (PTCA) balloon catheter inflated with liquid Rhenium in the redilated in-stent restenosis for 240-890, mean 384+/-125 s with low pressure (3 atm) in order to reach 30 Gy at 0.5 mm depth of the vessel wall. In 82 patients, intracoronary radiotherapy was carried out without complications, but one of the 83 patients who underwent sham procedure suffered small myocardial infarction. During follow-up, stent thrombosis with subsequent non-Q-wave myocardial infarction occurred in one patient in each group (6 days and 8 months after the procedure, respectively). At 6 months after the index procedure, repeat angiography was performed in 156 of the 164 patients with successful procedure (rate 95%): restenosis (stenosis >50% in diameter) or reocclusion was observed in only 19 of 78 (=24%) patients of the radiation but in 31 of 78 (=40%) patients of the sham procedure group (P=0.04). Event-free survival (free of death, myocardial infarction, target vessel revascularization) at 1 year was 87% for patients being radiated and 74% for patients having undergone sham procedure (P=0.05). CONCLUSIONS: Intracoronary radiation therapy with the liquid-filled beta-emitting Rhenium balloon is not only easy to perform, safe, and comparably inexpensive but also an effective option to prevent repeat restenosis and the need for target vessel revascularization in cases of in-stent restenosis.


Subject(s)
Angioplasty, Balloon, Coronary/methods , Coronary Restenosis/radiotherapy , Rhenium/therapeutic use , Aged , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Radioisotopes , Treatment Outcome
13.
Int J Cardiol ; 95(1): 29-34, 2004 May.
Article in English | MEDLINE | ID: mdl-15159034

ABSTRACT

BACKGROUND: Intracoronary radiotherapy with beta- and gamma-emitters has been shown to reduce the risk of restenosis after balloon angioplasty and after coronary stenting. The present study addresses the question whether intracoronary radiotherapy using the (188)rhenium liquid-filled PTCA balloon system is feasible, safe and effective in cases of in-stent restenosis. Acute and long-term angiographic results as well as clinical events within 1 year after the procedure were evaluated. METHODS AND RESULTS: From September 1999 to April 2000, 41 patients (mean age 60+/-10 years, 33 male, 8 female) with symptomatic in-stent restenosis underwent repeat PTCA and immediate intracoronary brachytherapy. After successful repeat PTCA (residual stenosis less than 30% in diameter), a second standard PTCA catheter was inflated with liquid (188)rhenium in the redilated in-stent restenosis for 315-880, mean 540+/-155 s with low pressure (3 atm) in order to reach 30 Gy at 0.5 mm depth of the vessel wall. In all patients with successful reintervention, intracoronary radiotherapy was unproblematically performed; in 16 patients, 21 new stents were implanted during the procedure-either immediately before or after radiation therapy. During follow-up, four episodes of stent thrombosis with subsequent myocardial infarction occurred in three patients (8 days, 37 days, 5 months and 6 months after the procedure, respectively). This complication was seen exclusively in patients with newly implanted stents. One patient of the stent group died suddenly 46 days after the procedure. All 40 surviving patients underwent repeat angiography in cases of repeat angina or routinely 6 months after brachytherapy, respectively. In the redilated target vessels without new stenting, restenosis (stenosis >50% in diameter) or reocclusion was observed in only 5 of 25 (=20%) cases, but in the restented target lesions, in 10 of 15 (=67%). Event-free survival (death, myocardial infarction, TVR) at 1 year after repeat dilatation and subsequent brachytherapy was 80% for patients not newly stented, but only 44% for patients with new stents. CONCLUSIONS: Intracoronary radiation therapy with the liquid-filled beta-emitting (188)rhenium balloon is a safe and effective therapy in cases of in-stent restenosis. The positive effect of irradiation, however, is abolished if a new stent is needed. In the not newly stented patients, 1-year follow-up is encouraging.


Subject(s)
Angioplasty, Balloon, Coronary , Brachytherapy , Coronary Restenosis/therapy , Radioisotopes/therapeutic use , Rhenium/therapeutic use , Aged , Combined Modality Therapy , Coronary Angiography , Coronary Restenosis/diagnostic imaging , Coronary Vessels/radiation effects , Coronary Vessels/surgery , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Postoperative Complications/mortality , Retrospective Studies , Survival Analysis , Time , Time Factors , Treatment Outcome
14.
J Nucl Med ; 44(6): 953-60, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12791825

ABSTRACT

UNLABELLED: 188Re-Hydroxyethylidene diphosphonate ((188)Re-HEDP) was used in previous studies for the palliative treatment of metastatic bone pain. However, the kinetic and radiation-absorbed doses have not been well documented. Therefore, the aim of this study was to gather dosimetric data for (188)Re-HEDP. METHODS: Thirteen prostate cancer patients with skeletal involvement were treated with 2,700-3,459 MBq (mean dose, 3,120 MBq) (188)Re-HEDP. Patients underwent whole-body scans 3, 20, and 28 h after therapy. The effective half-life, residence time, and radiation-absorbed dose values were calculated for the whole body, bone marrow, kidneys, and bladder as well as for 29 bone metastases. The urinary excretion rate was determined in 6 urine samples of each patient collected over 48 h at 8-h intervals beginning immediately after the administration of (188)Re-HEDP. After injection of (188)Re-HEDP, blood samples were taken weekly for 6 wk, and platelet and leukocyte counts were performed. RESULTS: The mean effective half-life was 15.9 +/- 3.5 h in bone metastases, 10.9 +/- 2.1 h in the bone marrow, 11.6 +/- 2.1 h in the whole body, 12.7 +/- 2.2 h in the kidneys, and 7.7 +/- 3.4 h in the bladder. The following radiation-absorbed doses were calculated: 3.83 +/- 2.01 mGy/MBq for bone metastases, 0.61 +/- 0.21 mGy/MBq for the bone marrow, 0.07 +/- 0.02 mGy/MBq for the whole body, 0.71 +/- 0.22 mGy/MBq for the kidneys, and 0.99 +/- 0.18 mGy/MBq for the bladder. (188)Re-HEDP showed a rapid urinary excretion within the first 8 h after therapy, with 41% of the (188)Re-HEDP administered being excreted. Forty-eight hours after therapy, the excretion rate was 60% +/- 12%. Only 1 patient showed a decrease of platelet count below 100 x 10(9) counts/L. None of the patients presented with a decrease of leukocyte count below 3.0 x 10(9) counts/L. CONCLUSION: (188)Re-HEDP is an effective radiopharmaceutical used in the palliative treatment of metastatic bone pain. The radiation-absorbed dose is acceptable for bone pain palliation with low doses for the normal bone marrow and the whole body.


Subject(s)
Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Etidronic Acid/pharmacokinetics , Prostatic Neoplasms/pathology , Rhenium/pharmacokinetics , Whole-Body Counting/methods , Aged , Aged, 80 and over , Body Burden , Bone Marrow/metabolism , Etidronic Acid/administration & dosage , Etidronic Acid/blood , Etidronic Acid/urine , Half-Life , Humans , Injections, Intravenous , Kidney/metabolism , Male , Metabolic Clearance Rate , Middle Aged , Organometallic Compounds , Radiation Dosage , Radiometry/methods , Rhenium/administration & dosage , Rhenium/blood , Rhenium/urine , Tissue Distribution , Urinary Bladder/metabolism
15.
Eur J Nucl Med Mol Imaging ; 30(3): 431-9, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12722739

ABSTRACT

Reported metabolic patterns in myocardial stunning are not uniform. We investigated relative myocardial perfusion, glucose and fatty acid uptake using a technetium-99 hexakis-2-methoxyisobutyl-isonitrile (MIBI), fluorine-18 2-fluoro-2-deoxyglucose (FDG) and iodine-125 15-(p-iodo-phenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) mixture, in a recently developed transgenic (TR) mouse model which mimics stunned myocardium. Twenty-seven mice - 14 TR and 13 age-matched wild type controls (C) - were divided into four groups: TR-fed, TR-fasted, C-fed and C-fasted. Animals were sacrificed 2 h after injection, tissue samples counted and percent-injected dose/gram tissue (% id/g) calculated for each radioisotope. Tissues were also Folch extracted and 125I incorporation into the various lipid pools (TG, triglycerides; DG, diglycerides; FFA, free fatty acids; PL, phospholipids) was determined by thin-layer chromatography (TLC). The pooled data for each of the four groups (TR-fed vs C-fed and TR-fed vs C-fasted) showed no differences in myocardial blood flow (% MIBI id/g), glucose uptake (% FDG id/g) or fatty acid uptake (% BMIPP id/g). Only minor differences were observed in the incorporation of 125I-BMIPP into the myocardial TG, DG, FFA and PL lipid pools. However, significantly decreased myocardial FDG uptake was observed in a subset of fasted mice - four out of ten TR-fasted mice (3.4% vs 20.5% id/g) and three out of nine C-fasted mice (5.5% vs 30.6% id/g). The transgenic mouse model of stunned myocardium shows normal myocardial perfusion and overall intact myocardial glucose and myocardial fatty acid uptake as determined with clinically applicable radiolabelled analogues. These data are in line with the hypothesis that the contractile inefficiency in stunned myocardium is not linked to metabolic alterations but is associated with an insufficient chemical to mechanical energy coupling.


Subject(s)
Fatty Acids/metabolism , Fatty Acids/pharmacokinetics , Fluorodeoxyglucose F18/pharmacokinetics , Glucose/metabolism , Iodobenzenes/pharmacokinetics , Myocardial Stunning/metabolism , Myocardial Stunning/physiopathology , Technetium Tc 99m Sestamibi/pharmacokinetics , Animals , Coronary Circulation , Fasting/metabolism , Mice , Mice, Transgenic , Myocardial Stunning/complications , Myocardial Stunning/diagnostic imaging , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/metabolism , Ventricular Dysfunction, Left/physiopathology
16.
BMC Nucl Med ; 1(1): 2, 2001.
Article in English | MEDLINE | ID: mdl-11734069

ABSTRACT

BACKGROUND: A study for pain relief therapy with 188Re-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 188Re-HEDP up to 60 mCi, with low bone marrow absorbed doses.

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