Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma.

INTRODUCTION: The unique expression pattern of fibroblast activation protein (FAP) in stromal and tumor cells, particularly in sarcomas, and its absence in normal tissues, have positioned it as a promising theragnostic approach for the detection and treatment of various cancer types. The objective of this prospective study is to assess the feasibility, safety, biodistribution, and therapeutic efficacy of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma. PATIENTS AND METHODS: Eight patients with advanced metastatic sarcoma, who were unresectable or had experienced disease recurrence following conventional treatments, underwent PTRT (peptide-targeted radionuclide therapy) using [177Lu]Lu-FAPI-2286. Prior to the treatment, confirmation of tumor uptake was obtained through [68Ga]Ga-FAPI-2286 PET/CT. RESULTS: After four cycles of PTRT with [177Lu]Lu-FAPI-2286 (6660-7400 MBq), with a 6-8-week interval between each cycle, no grade 3 or 4 side effects were observed in the patients, and the treatment was well tolerated by all participants. The results demonstrated a 52.37% reduction in the average volume of the primary tumor, accompanied by a significant decrease in SUVmax and TBR of the metastatic lesions (29.67% and 43.66% respectively), especially in cases of lung metastasis. Furthermore, besides the improvement in physical capacity, there was a noticeable reduction in pain, an increase in overall survival, and enhanced satisfaction with the treatment reported by the patients. CONCLUSION: [177Lu]Lu-FAPI-2286 PTRT, utilized for diverse cancer types, exhibited favorable tolerability in sarcoma patients, with minimal side effects, long-lasting retention of the radiopeptide within the tumor, and promising therapeutic effects. Preliminary findings of this prospective study need to be confirmed through further clinical trials.

First Experience of Radionuclide Therapy With 177Lu-FAPI-2286 in a Patient With Metastatic Mediastinal Sarcoma.

ABSTRACT: Fibroblast activation protein (FAP) is a new promising molecular target for theragnostic approach. FAP inhibitors (FAPIs) labeled with 177Lu could be potentially a therapeutic radiopharmaceutical. Here, we presented the experience of 4 cycles of 177Lu-FAPI in a 67-year-old man with an unresectable mediastinal sarcoma.

Complete Resolution of Locally Advanced Prostate Cancer After Molecular Endoradiotherapy With 177 Lu-PSMA.

ABSTRACT: A 76-year-old man with castration-resistant prostate cancer underwent 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT for restaging. A large PSMA-avid tumor with invasion to adjacent organs was noted causing gross hematuria and symptomatic anemia. Two cycles of 177 Lu-PSMA were administered, and the patient showed significant reduction of hematuria as well as declining in PSA levels. 177 Lu-PSMA therapy can be a good treatment option in patients with locally invasive tumors.

[68Ga]Ga-FAP-2286, a novel promising theragnostic approach for PET/CT imaging in patients with various type of metastatic cancers.

BACKGROUND: Fibroblast activation protein (FAP) has emerged as a promising target for diagnosis and therapeutic intervention due to high expression and accumulation in the stromal compartments of a variety of malignant tumors. FAP-2286 utilizes cyclic peptides with FAP-binding characteristics to enhance the retention of the imaging agent within tumors, in contrast to the small-molecule FAP inhibitors (FAPI) like FAPI-04/46. The aim of this study was to quantify the tumor uptake of [68Ga] Gallium-FAP-2286 within primary solid tumors, adjacent excised tissues, and metastatic lesions. METHODS: In this prospective study, 21 patients (average age 51.9) with various diagnoses of remaining and metastatic cancers participated. Among them, six had metastatic sarcoma, and 14 had adenocarcinoma, including eight breast, two rectum, two lung, two pancreas, and one thyroid cases. The patients underwent a [68Ga]Ga-FAP-2286 PET/CT scan. An hour post-administration of [68Ga]Ga-FAP-2286, a visual assessment of whole body scans and semi-quantification of the PET/CT results were carried out. The standardized uptake values (SUV)max of [68Ga]Ga-FAP-2286 in tumor lesions and the tumor-to-background ratio (TBR) were then calculated. RESULTS: The vital signs of the patients, such as heart rate, blood pressure, and temperature, were observed before, during, and after the diagnostic procedure during the 4-h follow-up. All individuals underwent the [68Ga]Ga-FAP-2286 PET/CT scans without any signs of drug-associated pharmacological effects. The PET/CT scans displayed substantial absorption of [68Ga]Ga-FAP-2286 in tumor lesions in all patients (100% (21/21)). Irrespective of the tumors' origins (epithelial or mesothelium) and whether they exhibited local recurrence, distant recurrence, or metastatic lesions, the PET/CT scans revealed the uptake of [68Ga]Ga-FAP-2286 in these lesions. CONCLUSION: Overall, these data suggest that [68Ga]Ga-FAP-2286 is a promising FAP derivative for efficient metastatic cancer diagnosis and being considered as a potential compound for therapeutic application in patients with advanced metastatic cancers.

SPECT/CT, PET/CT, and PET/MRI for Response Assessment of Bone Metastases.

Recent developments in hybrid SPECT/CT systems and the use of cadmium-zinc-telluride (CZT) detectors have improved the diagnostic accuracy of bone scintigraphy. These advancements have paved the way for novel quantitative approaches to accurate and reproducible treatment monitoring of bone metastases. PET/CT imaging using [18F]F-FDG and [18F]F-NaF have shown promising clinical utility in bone metastases assessment and monitoring response to therapy and prediction of treatment response in a broad range of malignancies. Additionally, specific tumor-targeting tracers like [99mTc]Tc-PSMA, [68Ga]Ga-PSMA, or [11C]C- or [18F]F-Choline revealed high diagnostic performance for early assessment and prognostication of bone metastases, particularly in prostate cancer. PET/MRI appears highly accurate imaging modality, but has associated limitations notably, limited availability, more complex logistics and high installation costs. Advances in artificial intelligence (Al) seem to improve the accuracy of imaging modalities and provide an assistant role in the evaluation of treatment response of bone metastases.

Bone Metastasis in Prostate Cancer: Bone Scan Versus PET Imaging.

Prostate cancer is the second most common cause of malignancy among men, with bone metastasis being a significant source of morbidity and mortality in advanced cases. Detecting and treating bone metastasis at an early stage is crucial to improve the quality of life and survival of prostate cancer patients. This objective strongly relies on imaging studies. While CT and MRI have their specific utilities, they also possess certain drawbacks. Bone scintigraphy, although cost-effective and widely available, presents high false-positive rates. The emergence of PET/CT and PET/MRI, with their ability to overcome the limitations of standard imaging methods, offers promising alternatives for the detection of bone metastasis. Various radiotracers targeting cell division activity or cancer-specific membrane proteins, as well as bone seeking agents, have been developed and tested. The use of positron-emitting isotopes such as fluorine-18 and gallium-68 for labeling allows for a reduced radiation dose and unaffected biological properties. Furthermore, the integration of artificial intelligence (AI) and radiomics techniques in medical imaging has shown significant advancements in reducing interobserver variability, improving accuracy, and saving time. This article provides an overview of the advantages and limitations of bone scan using SPECT and SPECT/CT and PET imaging methods with different radiopharmaceuticals and highlights recent developments in hybrid scanners, AI, and radiomics for the identification of prostate cancer bone metastasis using molecular imaging.

Development and evaluation of 89Zr-trastuzumab for clinical applications.

Objectives: Due to the suitable physical characteristics of 89Zr as a PET radionuclide and affinity of Trastuzumab monoclonal antibody against HER2, [89Zr]Zr-Trastuzumab was prepared and went through preclinical evaluations for ultimate human applications. Methods: 89Zr was produced by using 89Y(p,n)89Zr reaction at a 30 MeV cyclotron (radionuclide purity>99.9%, specific activity of 17 GBq/µg). p-SCN-Bn-Deferoxamine (DFO); was conjugated to trastuzumab, followed by labeling with 89Zr in oxalate form at optimized condition. Cell binding, internalization and, radioimmuno-activity assays were studied using HER2+ BT474 and HER2- CHO cell lines. Finally, the biodistribution of the radioimmunoconjugate was assessed in normal and HER2+ BT474 tumor-bearing mice using tissue counting and imaging at different intervals after injection. Also, a woman with HER2-positive metastatic breast cancer under treatment with Herceptin underwent both [89Zr]Zr-Trastuzumab and, [18F]FDG PET/CTs. Results: 89Zr was produced with high radionuclidic and radiochemical purities (>99%) and [89Zr]Zr-DFO-Trastuzumab was prepared with radiochemical purity of >98% and specific activity of 9.85 GBq/µmol. The radioimmunoconjugate was stable both in PBS buffer and in human serum for at least 48 h. The radioimmunoactivity assay demonstrated about 70% of [89Zr]Zr-DFO-Trastuzumab is bound to the BT474 cells at the number of 250×106 cells. Cell binding studies showed that about 28% of radioimmunoconjugate is attached to BT474 cells after 90 min. Internalization studies showed that 50% of [89Zr]Zr-Trastuzumab is internalized to BT474 cells only in 6 h. The biodistribution study of the labeled compound in normal mice demonstrated the same pattern of the monoclonal antibodies which is entirely different from the biodistribution of free 89Zr. Biodistribution and imaging studies in tumor-bearing mice showed the significant uptake values of [89Zr]Zr-Trastuzumab in tumor sites. [89Zr]Zr-Trastuzumab PET/CT revealed metastatic lesions documented previously with [18F]FDG PET/CT scan in a woman with breast cancer who was under treatment with Herceptin. Although the [18F]FDG PET/CT scan had better quality images, the valuable and unique advantage of [89Zr]Zr-Trastuzumab PET/CT is delineating HER2+ metastasis, which is essential in diagnosis and HER2-based treatments. Conclusion: The prepared [89Zr]Zr-Trastuzumab has a high potential radio-pharmaceutical for immune-PET imaging of the patients with HER2+ tumors.

Predictive and prognostic potential of pretreatment 68Ga-PSMA PET tumor heterogeneity index in patients with metastatic castration-resistant prostate cancer treated with 177Lu-PSMA.

Introduction: This study was conducted to evaluate the predictive values of volumetric parameters and radiomic features (RFs) extracted from pretreatment 68Ga-PSMA PET and baseline clinical parameters in response to 177Lu-PSMA therapy. Materials and methods: In this retrospective multicenter study, mCRPC patients undergoing 177Lu-PSMA therapy were enrolled. According to the outcome of therapy, the patients were classified into two groups including positive biochemical response (BCR) (≥ 50% reduction in the serum PSA value) and negative BCR (< 50%). Sixty-five RFs, eight volumetric parameters, and also seventeen clinical parameters were evaluated for the prediction of BCR. In addition, the impact of such parameters on overall survival (OS) was evaluated. Results: 33 prostate cancer patients with a median age of 69 years (range: 49-89) were enrolled. BCR was observed in 22 cases (66%), and 16 cases (48.5%) died during the follow-up time. The results of Spearman correlation test indicated a significant relationship between BCR and treatment cycle, administered dose, HISTO energy, GLCM entropy, and GLZLM LZLGE (p<0.05). In addition, according to the Mann-Whitney U test, age, cycle, dose, GLCM entropy, and GLZLM LZLGE were significantly different between BCR and non BCR patients (p<0.05). According to the ROC curve analysis for feature selection for prediction of BCR, GLCM entropy, age, treatment cycle, and administered dose showed acceptable results (p<0.05). According to SVM for assessing the best model for prediction of response to therapy, GLCM entropy alone showed the highest predictive performance in treatment planning. For the entire cohort, the Kaplan-Meier test revealed a median OS of 21 months (95% CI: 12.12-29.88). The median OS was estimated at 26 months (95% CI: 17.43-34.56) for BCR patients and 13 months (95% CI: 9.18-16.81) for non BCR patients. Among all variables included in the Kaplan Meier, the only response to therapy was statistically significant (p=0.01). Conclusion: This exploratory study showed that the heterogeneity parameter of pretreatment 68Ga-PSMA PET images might be a potential predictive value for response to 177Lu-PSMA therapy in mCRPC; however, further prospective studies need to be carried out to verify these findings.

Amino acid extravasation: a rare red flag to keep in mind during peptide receptor radioligand therapy (PRRT) with [177Lu]Lu-DOTATATE.

A 64 years-old woman with intestinal neuroendocrine tumor (NET) and multiple liver metastases was referred for peptide receptor radioligand therapy (PRRT) with [177Lu]Lu-DOTATATE. A few days after the third cycle of PRRT, erythema and swelling in the injection site is occurred which progressed up to one-month post-therapy. The cutaneous lesion was managed by a plastic surgeon with topical treatment. Amino acid extravasation could have devastating effects and should always be considered in patients who underwent PRRT and who receive amino acids for nephroprotection.

68 Ga-FAPI-46 PET/CT in a Metastatic Castration-Resistant Prostate Cancer Patient With Low PSMA Expression.

ABSTRACT: A 70-year-old man with mCRPC (metastatic castration-resistant prostate cancer) was referred for 68 Ga-PSMA PET/CT for restaging and the possibility of targeted molecular radioligand therapy with 177 Lu-PSMA. Numerous 68 Ga-PSMA-avid skeletal metastases with low SUVs were noted. Because of low PSMA expression, a 68 Ga-FAPI-46 PET/CT was performed to evaluate the eligibility for FAPI-based radioligand therapy. There were some discordant findings between 68 Ga-PSMA and 68 Ga-FAPI PET/CT scans regarding the detectability of lesions and SUVs. Our case signifies that 68 Ga-FAPI theragnostic may have a potential role in the treatment of mCRPC patients with insignificant PSMA expression or in cases after the failure of 177 Lu-PSMA therapy.

68 Ga-FAPI-46 and 18 F-FDG in Advanced Metastatic Pancreatic Cancer.

ABSTRACT: Recently imaging with new PET radiotracers that act as fibroblast activation protein inhibitors (FAPIs) showed promising results in oncology and even nononcology imaging. Here we report a case of advanced pancreatic adenocarcinoma, imaged with both 18 F-FDG and 68 Ga-FAPI-46 PET/CT scans. The result indicated that imaging with 68 Ga-FAPI-46 showed significant improvement in detection of metastases as well as local malignancy recurrence. Moreover, the intensity and SUVs of the lesions were higher in 68 Ga-FAPI-46 scan compared with 18 F-FDG.

Fibroblast Activation Protein Inhibitor Imaging and Therapy in a Patient With Multiple Endocrine Neoplasia Type 2A Syndrome.

ABSTRACT: A patient with multiple endocrine neoplasia type 2A syndrome who had exhausted several surgeries and radiotherapy was referred to nuclear medicine department for theranostic approaches. [68Ga]-DOTATATE PET/CT and [131I]I-mIBG SPECT/CT were performed, but the degree of uptake was insufficient for using the treatment companion of these tracers. Finally, 1 year later, [68Ga]-FAPI-46 PET/CT showed progressive disease with metastases to the lung, liver, bone, and lymph nodes with intense [68Ga]-FAPI-46 uptake. Treatment with [177Lu]Lu-FAPI-46 was done, and the patient tolerated treatment and showed evidence of clinical improvement following therapy.

Efficacy, safety and prognostic factors affecting overall survival among metastatic prostate cancer patients undergoing treatment with 177Lu-PSMA-617: A single center study.

BACKGROUND: Determining the efficacy, safety, and prognostic factors affecting overall survival (OS) among metastatic prostate cancer patients undergoing PSMA-targeted radioligand therapy (PRLT). METHOD: In this retrospective study, from November 2016 and December 2019, 43 heavily pretreated (90.7% on 1st line androgen deprivation therapy (ADT), 53.5% on 2nd line ADT, 58.1% on docetaxel) metastatic prostate cancer patients with median age of 71 years (range: 51-88 years) were enrolled. Treatment cycles were repeated every 8 weeks (range: 6-12 weeks). To evaluate the biochemical response after each cycle, prostate specific antigen (PSA) levels were measured and analyzed according to the Prostate Cancer Working Group 3 (PCWG3) criteria cutoffs. Possible adverse events after therapy were retrospectively classified according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. Kaplan-Meier and multivariable Cox proportional hazard regression analyses were used to identify factors associated with OS. RESULTS: A total of 112 cycles of PRLT with a median of 3 cycles (range: 1-6) and median administered activity per cycle of 6.29 GBq (range: 4.45-7.7 GBq) were used. PSA decline was observed in 65.1% of patients, and best PSA decline of ≥50% and ≥90% were achieved in 39.5% and 23.3% of patients, respectively. Major (grade III) anemia and thrombocytopenia occurred in 11.6% and 7% of patients, respectively. Median OS and median PSA progression-free survival were 52 and 20 weeks, respectively. In univariate analysis, baseline hemoglobin <11.2 g/dL, baseline platelets count ≥327,000/µL, PSA decline <20.94% after first cycle of therapy, Eastern Cooperative Oncology Group (ECOG) >2, baseline PSA ≥ 115 ng/mL, cumulative dose of 177Lu-PSMA <12.95 GBq, initial alkaline phosphatase ≥196.5 U/L, initial lactate dehydrogenase ≥380 U/L and superscan pattern in bone scintigraphy were associated with worse OS. In multivariable Cox regression analysis, higher baseline platelet count, lower baseline hemoglobin, superscan pattern, and lower cumulative dose of 177Lu-PSMA remained significant predictors of poor OS. CONCLUSION: PRLT with 177Lu-PSMA is well-tolerated and effective in metastatic prostate cancer patients who have no other treatment options available. The novel prognostic markers found in this study (high platelet count, superscan pattern) were associated with poor overall survival.

Feasibility and Therapeutic Potential of 177Lu-Fibroblast Activation Protein Inhibitor-46 for Patients With Relapsed or Refractory Cancers: A Preliminary Study.

INTRODUCTION: Fibroblast activation protein (FAP) is a member of the serine protease family and has a high expression in the stroma of approximately 90% of epithelial malignancies. The present investigation aimed to assess the feasibility, safety, and dosimetry data of 177Lu-FAPI-46 in diverse malignancies. PATIENTS AND METHODS: Patients with advanced cancers with nonoperable tumors, or tumors refractory to conventional therapies, were enrolled. Treatment included escalating doses of 177Lu-FAPI-46 (1.85-4.44 GBq) per cycle using a combination of clinical and statistical expertise design, and intervals of 4 to 6 weeks were considered between the cycles. Biodistribution and dosimetry were examined by whole-body scans. We applied the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 to measure peptide-targeted radionuclide therapy (PTRT)-associated toxicity. RESULTS: A total of 21 patients (11 females and 10 males) with a median age of 50 years (range, 6-79 years) were investigated. Of 21 participants, 18 cases were selected for PTRT. Overall, 36 PTRT cycles were performed. The median number of PTRT cycles and the median injected amount of activity in each cycle were 2 and 3.7 GBq, respectively. The dosimetric analysis revealed median absorbed doses of 0.026, 0.136, 0.886, and 0.02 with ranges of 0.023-0.034, 0.001-0.2, 0.076-1.39, and 0.002-0.2 mGy/MBq for the whole body, liver, kidneys, and spleen, respectively. The therapy was well tolerated in almost all patients. CONCLUSIONS: The findings of this preliminary investigation might indicate the potential feasibility and safety of PTRT using 177Lu-FAPI-46 for different aggressive tumors. Moreover, the current study could be beneficial in determining the suitable amount of activity for a phase 2 study.

177Lu-EDTMP for Metastatic Bone Pain Palliation: A Systematic Review and Meta-Analysis.

Purpose: Painful metastatic bone involvement is common in advanced stages of many cancers. Between available radionuclides for bone pain palliation, no consensus has been reached on lutetium ethylenediaminetetramethylene phosphonate (177Lu-EDTMP) administration in this milieu. The aim of this study is to evaluate the treatment efficacy, safety profile, and toxicities of 177Lu-EDTMP in patients with metastatic bone involvement, according to the published literature. Methods: A comprehensive literature search of PubMed/MEDLINE, Scopus, and Google Scholar databases was carried out to retrieve pertinent articles published until January 2019, concerning the clinical efficacy and safety of 177Lu-EDTMP for bone pain palliative purposes. Results: Eight studies (172 patients) were included. This analysis revealed statistically significant effect of 177Lu-EDTMP therapy on the visual analog score (4.84% (95% CI: 3.88-5.81; p < 0.001), bone palliative pain response (84%, 95% CI: 75%-90%; p < 0.001), and Karnofsky performance status (21%, 95% CI: 18%-24%; p < 0.001) overall (as well as in the high-dose and low-dose subgroups). Complete palliative pain response to treatment was observed in 32% (95% CI: 16%-53%) of patients receiving 177Lu-EDTMP. Anemia was found to be the most common hematologic toxicity imposed by this therapeutic approach (grade I/II anemia in 24% (95% CI: 14%-38%; p < 0.001) and grade III/IV anemia in 19% (95% CI: 12%-28%; p < 0.001)). Conclusions: 177Lu-EDTMP seems to have comparable efficacy and safety profile as that of the frequently administered radiopharmaceuticals for bone palliation. Therefore, this agent can be a good option for bone pain palliative purposes, in case of limited access to other bone palliative radiopharmaceuticals.

Targeted Palliative Radionuclide Therapy for Metastatic Bone Pain.

Bone metastasis develops in multiple malignancies with a wide range of incidence. The presence of multiple bone metastases, leading to a multitude of complications and poorer prognosis. The corresponding refractory bone pain is still a challenging issue managed through multidisciplinary approaches to enhance the quality of life. Radiopharmaceuticals are mainly used in the latest courses of the disease. Bone-pain palliation with easy-to-administer radionuclides offers advantages, including simultaneous treatment of multiple metastatic foci, the repeatability and also the combination with other therapies. Several ߯- and α-emitters as well as pharmaceuticals, from the very first [89Sr]strontium-dichloride to recently introduced [223Ra]radium-dichloride, are investigated to identify an optimum agent. In addition, the combination of bone-seeking radiopharmaceuticals with chemotherapy or radiotherapy has been employed to enhance the outcome. Radiopharmaceuticals demonstrate an acceptable response rate in pain relief. Nevertheless, survival benefits have been documented in only a limited number of studies. In this review, we provide an overview of bone-seeking radiopharmaceuticals used for bone-pain palliation, their effectiveness and toxicity, as well as the results of the combination with other therapies. Bone-pain palliation with radiopharmaceuticals has been employed for eight decades. However, there are still new aspects yet to be established.

99m Tc-Octreotide-Avid Brain Mass In A Patient With Poorly Differentiated Papillary Thyroid Carcinoma, Hope In Despair.

Brain metastases of PTC are rare and occur in 0.1-5% of the patients, especially in the poorly differentiated types that usually fail to concentrate iodine. We present a rare case of PTC with probable brain metastasis in a 58-year-old woman with a history of poorly differentiated PTC that showed elevated Tg levels and no metastasis was detected in the whole-body iodine scan, despite the positive 99m Tc-octreotide scintigraphy. This imaging modality could be helpful as a diagnostic guide for radionuclide therapy with labeled somatostatin analogs in cases of thyroid carcinoma with elevated Tg levels and negative whole-body iodine scan.

Whole-Body 177Lu-Prostate-Specific Membrane Antigen Scan Pattern With Excess Free 177Lu-Chloride in a Metastatic Castration-Resistant Prostate Cancer Patient.

A 56-year-old man with metastatic castration-resistant prostate cancer was referred for radioligand therapy with Lu-prostate-specific membrane antigen. In the third cycle, a posttherapy whole-body scan showed unexpected skeletal and joint uptake apart from his known metastatic lesions. This observation raised suspicion for possible impurity (mainly free lutetium) in the applied radiopharmaceutical product. After contacting the radiopharmaceutical company, we were informed that the radiochemical purity of the used batch of Lu-prostate-specific membrane antigen had been 95%. This is the first report of excess free lutetium scan pattern and its complications in a patient undergoing radioligand therapy.

Rhenium-188 radiosynovectomy for chronic haemophilic synovitis: Evaluation of its safety and efficacy in haemophilic patients.

INTRODUCTION: Radiocolloids labelled with less costly and more accessible radionuclides such as rhenium-188 are of interest to developing countries compared with those labelled with rhenium-186 and yttrium-90. AIM: This study was aimed to evaluate the efficacy and safety of radiosynovectomy using rhenium-188 in patients with chronic haemophilic synovitis and recurrent hemarthrosis. METHODS: In this quasi-experimental prospective study, 20 haemophilic patients were evaluated at preinjection, and at 1, 3, 6 and 12 months after injection. Magnetic resonance imaging (MRI) was done to measure synovial thickness and to calculate Denver score. Joint radiographs were taken to measure the Pettersson score. The Gilbert questionnaire, Functional Independence Score in Hemophilia (FISH) and visual analogue scale (VAS) for pain were completed, and the number of bleeding episodes and factor consumption were recorded at each follow-up visit. RESULTS: The number of bleeding episodes, the amount of factor consumption per month, VAS pain scores and synovial thickness decreased significantly over time (P < .05). Gilbert and FISH scores showed significant improvement (P < .001). However, Pettersson score and Denver score showed no significant changes after injection. Minor complications including temporary pain and swelling occurred in 20% of patients, and no major complication was observed after rhenium-188 injection. CONCLUSION: Our results indicated high clinical impact, efficacy, safety and low invasion of rhenium-188 in radiosynovectomy of haemophilic patients. Considering the availability and relatively low cost of rhenium-188 in developing countries, this can be a good treatment option for haemophilic patients with recurrent hemarthrosis, particularly when the synovial hypertrophy is not massive yet.