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1.  188Re radiopharmaceuticals for radiosynovectomy: evaluation and comparison of tin colloid, hydroxyapatite and tin-ferric hydroxide macroaggregates 
Radiosynovectomy is a therapy used to relieve pain and inflammation from rheumatoid arthritis and related diseases. In this study three 188Re particulate compounds were characterized according to their physico-chemical properties and their biological behavior in rabbits. The results were compared in order to establish which was the radiopharmaceutical that better fits the requirements of this kind of radiotherapy.
Three radiopharmaceutical formulations, tin colloid, hydroxyapatite particles (HA) and ferric hydroxide macroaggregates coated with tin colloid (FHMA), were physically characterized (number, volume and surface of the particles). For this purpose laser diffraction methodology was used. To evaluate cavity leakage of activity the following studies in New Zealand rabbits were performed: scintigraphic images for 48 hr after intraarticular injection of each radiopharmaceutical, biodistribution at 48 hr and urine samples collection during the first 24 hr post-radiopharmaceutical administration.
Labeling procedures for 188Re-HA and 188Re-Sn-FHMA were labour intensive while 188Re-Sn was easily prepared. Furthermore, 188Re-Sn colloid offered the greatest surface area in the 2–10 microm range and was obtained with a radiochemical purity over 95%, while percentage of bound activity for 188Re-HA and 188Re-Sn-FHMA were 55% and 92% respectively. Stability was verified for the three radiopharmaceuticals for 24 hr. Scintigraphic studies and biodistribution in rabbits after intraarticular administration of the radiopharmaceuticals showed relevant activity only in the knee, this being over 90% of the residual activity in the whole body at 48 hr in every case. Renal elimination of 188Re-Sn colloid and 188Re-Sn-FHMA was detected by activity measurements in urine samples, during the first 12 hr post-radiopharmaceutical injection.
The percentage of activity retained in the knee was 69.1% for 188Re-Sn colloid, 55.1% for 188Re-Sn-FHMA and 33.6% for 188Re-HA.
The 188Re-Sn colloid was easy to prepare, minimum facilities were required, was stable for 24 hr and showed minimal leakage from the joint after intraarticular injection into the rabbit's knee. Furthermore, 188Re-Sn colloid has greater retention in the knee when it is compared with the other radiopharmaceuticals, so it could provide the best therapeutic effect/absorbed dose ratio for the patient.
PMCID: PMC373254  PMID: 15040807
2.  Radiosynovectomy of Proximal Interphalangeal Joint Synovitis in Rheumatoid Arthritis Treated with Rhenium-188 Labeled Tin-colloid and Imaging with Single-photon Emission Computerized Tomography/Computed Tomography: A First Case Report 
World Journal of Nuclear Medicine  2015;14(3):216-218.
Rheumatoid arthritis (RA) is a chronic disease that is mainly characterized by the asymmetric erosive synovitis, particularly affecting peripheral joints. Radiation synovectomy or radiosynovectomy (RSV), also known as radiosynoviorthesis was first described in 1950's as an adjuvant treatment for RA. RSV is based on the irradiation of the joint synovium by the intra-articular administration of various β-emitting radiopharmaceuticals. As a generator-produced β-emitting radionuclide, the importance of rhenium-188 (Re-188) for radionuclide therapy is increasing rapidly. There are previous reports which used Re-188 tin colloid in knee joint synovitis, but use of Re-188 tin colloid in small joint is not yet reported. We describe the use of Re-188 tin colloid in a 45-year-old female who presented with right 4th proximal interphalangeal joint synovitis due to rheumatoid arthritis.
PMCID: PMC4564928  PMID: 26420996
Radiosynovectomy; rhenium-188 tin colloid; small joint; single-photon emission computerized tomography/computed tomography
3.  Radiosynovectomy in the Therapeutic Management of Arthritis 
Radiosynovectomy is a well-established therapy in arthritis and involves an intra-articular injection of small radioactive particles to treat a synovitis. In Europe, frequent indications are rheumatoid and poly-arthritis. Especially in Germany radiosynovectomy is the second common therapy in Nuclear Medicine with about 40,000–60,000 treated joints per year. In Spain, USA, Turkey, Argentines and Philippines the therapy is more use in hemophilic arthritis with excellent results. Especially in developing countries with low availability of clotting factors, the radiosynovectomy represent a cost effective therapeutic option for repeated bleedings in hemophilic arthropathy. The special focus in these countries is maintaining of mobility and work ability. Often only the knee and medium joints (ankle, elbow and shoulder) are treated using yttrium-90, rhenium-186 or phosphorus-32. However, in rheumatoid arthritis most common affected joints are the fingers. For the treatment in these small joints, erbium-169 is necessary. Unfortunately, erbium-169 is only available in Europe. Further indications for radiosynovectomy are osteoarthritis and the articular effusion after joint replacement. The reported response rates in rheumatoid and poly-arthritis range from 60% to 80% depends from the stage of previous arthrosis. The best effectiveness of therapy was observed in hemophilic arthritis with response rate of 90% and significant reducing of bleeding frequency. The therapy is well-tolerated with low rate of side effects. In respect of the specific uptake of particles in the synovia and short range of beta radiation, the radiation exposure outside the joint is very low. The radiosynovectomy has efforts in comparison to surgical synovectomy: it's a minor intervention with low costs; and simultaneous treatments of multiple joints or treatment in short intervals are possible. The presented paper summarized the published papers and reports our own experiences in >15,000 treated joints.
PMCID: PMC4337000  PMID: 25709538
Erbium-169; hemophilic arthritis; osteoarthritis; rhenium-186; rheumatoid arthritis; yttrium-90
4.  The Efficacy of Magnetic Resonance Imaging and X-Ray in the Evaluation of Response to Radiosynovectomy in Patients with Hemophilic Arthropathy 
Objective: We aimed to assess the role of Magnetic Resonance Imaging (MRI) and X-Ray in the evaluation of response to radiosynovectomy (RS) in patients with hemophilic arthropathy.
Material and Methods: Eleven patients who suffered from hemophilic arthropathy with a mean age of 11.7 (range between 7-15) were included in this study. 148-185 MBq Yttrium 90 silicate (Y-90) was administered intraarticularly to ten knee joints and one patient was treated with intraarticular 74 MBq Rhenium 186 (Re-186) injection into his ankle. Before radiosynovectomy, plain anteroposterior and lateral X-rays of the target joints were obtained by standard technique. The follow-up MRI and X-ray studies of the patients were done 6 months after RS. Pettersson hemophilic arthropathy scales were utilized to stage the condition of the joints on plain X-ray and classification of the investigated joints on MRI were done according to Denver score. The clinical assessment of the efficacy of the RS was made with the comparison of the average bleedings before and after the intervention.
Results: During the 6-month follow-up period after RS, an improvement in number of hemarthrosis 75% or greater compared with the prior six months occurred in six joints (54.5%). The Pettersson scores worsened in 1/11 (9%), remained unchanged in 9/11 (81.8%), and improved in 1/11 (9%) joints. At the 6-month follow-up, the MRI score worsened in one (9%) and was unchanged in 10/11 joints (90.9%).
Conclusion: MRI is a more sensitive tool than plain radiography for evaluating and follow-up of joint disease in persons with hemophilia, but both methods don’t show correlation with the therapeutic response
Conflict of interest:None declared.
PMCID: PMC3590945  PMID: 23487524
Radiosynovectomy; hemophilic arthropathy; magnetic resonance imaging; therapy response
5.  Efficacy of radiation synovectomy (radiosynovectomy or radiosynoviorthesis) with yttrium-90 in exudative inflammation of synovial membrane of knee joints in patients with rheumatic diseases – preliminary report 
Reumatologia  2016;54(1):3-9.
Hypertrophic and exudative synovitis of the knee is one of the earliest symptoms in rheumatic diseases. In the case of pharmacotherapy failure, other methods which directly remove the inflamed synovial membrane are used – synovectomies. Radiosynovectomy (RSV) is the radiopharmaceutical application of colloidal solution to joint cavities. In this study, the authors assessed the efficacy of knee radiosynovectomy with yttrium-90 (Y-90) in several groups of patients divided into certain rheumatic diseases.
Material and methods
The study group consisted of 70 patients aged from 29 to 65 years with hypertrophic and exudative synovitis of the knee in rheumatic diseases such as rheumatoid arthritis, osteoarthrosis and spondyloarthropathies. Radiopharmaceutical colloid of Y-90, with a radiation dose of 185-222 MBq in a volume of 2-3 ml, was administered to joint. Then the knee joint was immobilized for 72 h. During visits V1, V2, V3 and V4, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured and ultrasound of the knee was performed. Disease activity was evaluated by the WOMAC scale, HAQ and 100-mm visual analog scale (VAS).
The most significant difference of synovial hypertrophy, before and after the procedure, was obtained in patients with rheumatoid arthritis. Variability of effusion before and after the procedure in all groups was comparable and statistically significant. The greatest improvement in variability of inflammatory parameters, before and 4 weeks after radiosynovectomy, was observed in patients with rheumatoid arthritis.
In the therapeutic algorithm radiosynovectomy should be located between conservative treatment and operative procedures. Radiosynovectomy does not require hospitalization or prolonged rehabilitation. Radiosynoviorthesis affects the patient's general condition, which is associated with eliminating pain and restoring joint function.
PMCID: PMC4847323  PMID: 27407269
knee; hypertrophic-exudative synovitis; radiosynovectomy
6.  Consecutive radiosynovectomy procedures at 6-monthly intervals behave independently in haemophilic synovitis 
Blood Transfusion  2013;11(2):254-259.
Previous studies on the same group of patients investigated here demonstrated the effectiveness of radiosynovectomy in the treatment of chronic haemophilic synovitis even if one, two or three radiosynovectomy procedures (RS-1, RS-2, RS-3) may be necessary. The purpose of this study was to determine whether the joints’ response to each radiosynovectomy procedure behaved independently or not.
Materials and methods
One hundred and fifty-six radiosynovectomies were performed in 104 joints of 78 people diagnosed with chronic haemophilic synovitis. The patient’s mean age was 18 years. Fifty-eight patients required radiosynovectomy in a single joint, whereas 20 received treatment in more than one joint. Of the 104 joints subjected to radiosynovectomy, 33 were elbows, 47 knees and 24 ankles. Radiosynovectomy was carried out with either yttrium-90 or rhenium-186 (1–3 injections with 6-month intervals between them). Of the 104 joints, 68 required a single injection of the radioisotope (RS-1), 20 required two injections (RS-2) and 16 required three injections (RS-3). In eight cases (7.6%), the affected joints eventually required surgery.
An analysis of seven variables (number of bleeding episodes, articular pain, range of motion in flexion and extension, muscle strength in flexion and extension, and synovial thickness by imaging) demonstrated that each consecutive radiosynovectomy behaves independently in haemophilic synovitis.
Each consecutive radiosynovectomy behaves independently in haemophilic synovitis. This finding had not been documented in the literature before the present study.
PMCID: PMC3626478  PMID: 23245712
haemophilia; synovitis; radiosynovectomy
7.  Application of Rhenium-186 Radiosynovectomy in Elbow Diffuse Pigmented Villonodular Synovitis. - A Case Report with Multiple Joint Involvement 
After surgical therapy of diffuse pigmented villonodular synovitis (DPVNS), recurrence is seen in almost half of the patients. The effectiveness of radiosynovectomy (RSV) in preventing recurrence and complaints of DPVNS is well known. Elbow involvement in DPVNS is a very rare condition; therefore, RSV in elbow hasn’t been experienced widely. The aim of this case report is to show the effectiveness of RSV with rhenium-186 (Re-186) sulfide colloid. We applied Re-186 sulfide colloid to the elbow joint of DPVNS patients six weeks after arthroscopic synovectomy. As a result, the patient did not have any complaints, and our findings are compatible with residue or recurrence on magnetic resonance imaging (MRI) in sixth and twentieth month controls after administration. We concluded that Re-186 is an effective adjuvant therapy for the prevention of recurrence and complaints.
PMCID: PMC4043031  PMID: 24900063
Rhenium-186 (Re-186); Radiosynovectomy; Elbow; Diffuse Pigmented Villonodular Synovitis (DPVNS)
8.  Radiosynovectomy of Painful Synovitis of Knee Joints Due to Rheumatoid Arthritis by Intra-Articular Administration of 177Lu-Labeled Hydroxyapatite Particulates: First Human Study and Initial Indian Experience 
The aim of this study is to assess the effectiveness of Radiosynovectomy (RSV) using 177Lu-labeled hydroxyapatite (177Lu-HA) in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis (RA). Ten patients, diagnosed with RA and suffering from chronic painful resistant synovitis of the knee joints were referred for RSV. The joints were treated with 333 ± 46 MBq of 177Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS < 25), fair (VAS ≥ 25-50), good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of 177Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than those with more advanced changes (Steinbrocker's Grades III and IV) in terms of VAS improvement (75% vs. 45.8%) (P < 0.001). The overall success rate (VAS ≥ 50) was 80%. Remission of pain during the night was achieved in 100%, and knee flexibility was improved in 80%. The changes in the blood pool phase before RSV were 3.2 ± 0.7 and after the therapy 1.4 ± 0.7 (P < 0.001). The J/B ratio was: Before RSV 2.4 ± 0.3; after treatment 1.0 ± 0.2 (P < 0.05). CRP concentration 4 and 24 weeks after the therapy was significantly lower than before treatment. The fibrinogen level was not different before and after RSV. RSV side-effects assessed for the whole follow-up period were minor and not significant. RSV with 177Lu-HA was safe and effective in patients with knee joint chronic painful synovitis of rheumatoid origin. It exhibited significant therapeutic effect after 6 months follow-up period with no significant side-effects. The preliminary investigations reveal that 177Lu-labeled HA particles hold considerable promise as a cost-effective agent for RSV. More elaborate and controlled clinical trials are necessary to evaluate the therapeutic efficacy and safety of the agent compared with the treatment with other radionuclides and glucocorticosteroids.
PMCID: PMC4455177  PMID: 26097417
177Lu; hydroxyapatite; knee joint synovitis; radiation synovectomy
9.  Treatment of Diffuse Pigmented Villonodular Synovitis of the Knee with Combined Surgical and Radiosynovectomy 
HSS Journal  2008;5(1):19-23.
Treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large joints by isolated surgical resection is unsatisfactory, with high rates of local recurrence. Post-synovectomy adjuvant treatment with external beam radiation therapy or intra-articular injection of radioactive material as yttrium-90 (90Y) yielded better results. Between January 2005 and January 2007, 12 patients (eight men and four women aged 19–49 years) with extensive diffuse PVNS of the knee were treated. All patients had an adjuvant post-operative external beam radiation therapy (2,600–3,000 cGy) conventionally fractionated 200 cGy/fraction, five fractions/week, 6–8 weeks after surgery. Mean follow-up time was 27 months (range from 20 to 36 months). All patients were followed up using clinical assessment, magnetic resonance imaging, and plain X-ray. In all patients, neither evidence of disease recurrence nor progression of bone or articular destruction was noted. No complications were noticed after surgery or after post-operative external beam radiation therapy. A combination of debulking surgery using anterior and posterior approach with adjuvant post-operative external beam radiation therapy for extensive diffuse PVNS of the knee joint is a reliable treatment method, with good results in regard to the incidence of local recurrence and functional outcome.
PMCID: PMC2642543  PMID: 19096892
PVN; synovitis; radiosynovectomy; synovectomy
10.  Effects of intraarticular 32P colloid in the treatment of hemophilic synovitis of the knee: A short term clinical study 
Indian Journal of Orthopaedics  2016;50(1):55-58.
Chronic synovitis is a consequence of recurrent intraarticular hemorrhage in patients with hemophilia. Eventually, synovitis leads to degeneration of the articular cartilage, with serious consequences that impact the quality-of-life in hemophiliacs. The aim of our study was to investigate the short term clinical effects of intraarticular injection of the radionuclide preparation32P colloid (32P-labelled colloidal chromic phosphate suspension) on recurrent intraarticular hemorrhages in patients with hemophilic synovitis of the knee.
Materials and Methods:
Patients who met the inclusion criteria (n = 22) were enrolled in an open-label study between October 2011 and September 2012.32P colloid was injected into the knee joint and patients were followed up over 6 months after treatment. Hemorrhage frequency, visual analog scale pain score, hospital for special surgery knee score, knee circumference, upper knee circumference, knee diameter, and knee range of motion (ROM) were compared before and after treatment with intraarticular32P colloid injection.
In 24 knees evaluated in 22 participating patients, there was a significant reduction in the number of hemorrhages after32P colloid treatment, along with significant pain relief. However, there were no statistically significant changes in the degree of joint swelling, degree of muscle atrophy and knee ROM between the pre and post treatment evaluations.
The frequency of joint hemorrhage in patients with hemophilic knee synovitis can be significantly reduced and local symptoms can be improved in the short term by intraarticular injection of32P colloid.
PMCID: PMC4759875  PMID: 26955177
32P colloid; hemophilia; intraarticular injection; radiosynovectomy; synovitis; Knee joint; hemophilia; synovia; synovitis; radionuclides
11.  Role of radiosynovectomy in the treatment of rheumatoid arthritis and hemophilic arthropathies 
Radiosynovectomy is a novel method of treatment for several acute and chronic inflammatory joint disorders. A small amount of a beta-emitting radionuclide is injected into the affected joint delivering a radiation dose of 70 to 100 Gy to the synovia. The proliferative tissue is destroyed, secretion of fluid and accumulation of inflammation causing cellular compounds stops and the joint surfaces become fibrosed, providing long term symptom relief. The radionuclides are injected in colloidal form so that they remain in the synovium and are not transported by lymphatic vessels causing radiation exposure to other organs. Complete reduction of knee joint swelling has been seen in above 40% and pain relief in 88% of patients. Wrist, elbow, shoulder, ankle and hip joints showed significant improvement in 50-60% and restoration of normal function and long term pain relief has been achieved in about 70% of small finger joints. In hemophilic arthropathies complete cessation of bleeding in about 60% and improved mobility in 75% of patients has been reported.
PMCID: PMC3097689  PMID: 21614297
Radiosynovectomy; treatment of hemophilic arthropathies; radionuclides in rheumatoid arthritis
12.  Development of 166Ho-phytate Complex for Radiosynovectomy 
66Ho-chloride was obtained by bombardment of natural Ho(NO3)3 dissolved in acidic media using thermal neutron flux (4-5 × 1013
166Ho-holmium chloride (185 MBq) was used successfully for preparation of 166Ho-phytate complex with high radiochemical purity (>99.9 %, ITLC, MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase). The complex stability and viscosity were checked in the final solution up to 2 days. The prepared complex solution (60 μCi/100 μl) was injected intraarticularly to male rat knee joints. Leakage of radioactivity from the injection site and its distribution in organs were investigated up to 2 days.
Approximately all of the injected dose had remained in the injection site 2 days after injection.
The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology.
PMCID: PMC4043017  PMID: 24899986
Phytate; Radiosynovectomy; Holmium-166; Biodistribution; SPECT
13.  Development of 177Lu-phytate Complex for Radiosynovectomy 
Objective(s): In this work a new possible agent for radiosynovectomy has been targeted for articular pain palliation.
Materials and Methods: Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4 × 1013 The product was converted into chloride form which was further used for labeling of 177Lu-phytate complex and checked using ITLC (MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase). The complex stability and viscosity were checked in the final solution up to seven days. The prepared complex solution (100 µCi/100 µl) was injected intra-articularly to male rat knee joint. Leakage of radioactivity from injection site and its distribution in organs were investigated up to seven days.
Results: The complex was successfully prepared with high radiochemical purity (>99.9 %). Approximately, the whole injected dose has remained in injection site seven days after injection.
Conclusion: The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology.
PMCID: PMC3700046  PMID: 23826493
Biodistribution; Lutetium-177; Phytate Radiosynovectomy
14.  Preparation and evaluation of Lu-177 phytate Complex for Radiosynovectomy 
Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4 × 1013 n/cm/s. The product was converted into chloride form which was further used for labeling of Lu-177 phytate complex successfully with high radiochemical purity (>99.9%, instant thin layer chromatography, MeOH: H2O: Acetic acid, 4:4:2, as mobile phase). The complex stability and viscosity were checked in the final solution up to 7 days. The prepared complex solution (100 μCi/100 μl) was injected intra-articularly to the male rat knee joint. Leakage of radioactivity from the injection site and its distribution in organs were investigated up to 7 days. Approximately, all injected dose has remained in injection site 7 days after injection. The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology.
PMCID: PMC4149764  PMID: 25191108
Biodistribution; lutetium-177; phytate; radiosynovectomy
15.  Radiosynovectomy in rheumatic diseases 
Journal of Ultrasonography  2014;14(58):241-251.
Radiosynovectomy is a safe and repeatable treatment method of chronic synovitis with synovial overgrowth and refractory chronic or acute inflammatory joint effusion. It consist in the intraarticular administration of a radioactive isotope in the form of a colloid causing the extinguishing of active synovitis. The radiocolloid causes permanent irradiation of the synovium with beta ray electron beams, which ultimately leads to its fibrosis and extinguishes the inflammatory process destroying the joint.
The main indications for radiosynovectomy include chronic and acute arthritis in the course of systemic diseases, intraarticular bleeding in hemorrhagic diatheses (hemophilia), selected cases of osteoarthritis, recurrent effusions following surgery, e.g. arthroplasty, or other iatrogenic post-surgery complications causing arthritis. Radiosynovectomy is also performed in pigmented villonodular synovitis and crystal synovitis. The most common method used to determine the eligibility for radiosynovectomy is an ultrasound, which shows the location and activity of the thickened synovium. The administration of a radiocolloid into the joint, sheath or bursa should also be performed under the control of the ultrasound image, as this ensures a precise location of the puncture needle and full control of the isotope administration process. Clinical efficacy of radiosynovectomy depends on the proper qualification of patients for the procedure. The success rate of radiosynovectomy in common indications is 65–80%. It is confirmed by the visualization of avascular (fibrotic) synovium in follow-up ultrasound tests. The aim of this article is to present techniques and indications for the radiosynovectomy treatment.
PMCID: PMC4579679  PMID: 26673861
radiosynovectomy; synovitis; arthritis; rheumatoid arthritis; osteoarthritis
16.  Size Control of 99mTc-tin Colloid Using PVP and Buffer Solution for Sentinel Lymph Node Detection 
Journal of Korean Medical Science  2015;30(6):816-822.
Colloidal particle size is an important characteristic that allows mapping sentinel nodes in lymphoscintigraphy. This investigation aimed to introduce different ways of making a 99mTc-tin colloid with a size of tens of nanometers. All agents, tin fluoride, sodium fluoride, poloxamer-188, and polyvinylpyrrolidone (PVP), were mixed and labeled with 99mTc. Either phosphate or sodium bicarbonate buffers were used to adjust the pH levels. When the buffers were added, the size of the colloids increased. However, as the PVP continued to increase, the size of the colloids was controlled to within tens of nanometers. In all samples, phosphate buffer added PVP (30 mg) stabilized tin colloid (99mTc-PPTC-30) and sodium bicarbonate solution added PVP (50 mg) stabilized tin colloid (99mTc-BPTC-50) were chosen for in vitro and in vivo studies. 99mTc-BPTC-50 (<20 nm) was primarily located in bone marrow and was then secreted through the kidneys, and 99mTc-PPTC-30 (>100 nm) mainly accumulated in the liver. When a rabbit was given a toe injection, the node uptake of 99mTc-PPTC-30 decreased over time, while 99mTc-BPTC-50 increased. Therefore, 99mTc-BPTC-50 could be a good candidate radiopharmaceutical for sentinel node detection. The significance of this study is that nano-sized tin colloid can be made very easily and quickly by PVP.
Graphical Abstract
PMCID: PMC4444485  PMID: 26028937
Sentinel Lymph Node; Lymphoscintigraphy; 99mTc-tin Colloid; Polyvinylpyrrolidone (PVP)
17.  Analysis of lapine cartilage matrix after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate 
Objective: To study the short and long term effects of radiosynovectomy on articular cartilage in growing and mature rabbits.
Methods: The articular cartilage of the distal femurs of rabbits was examined four days, two months, and one year after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate ([166Ho]FHMA). Arthritic changes were evaluated from histological sections by conventional and polarised light microscopy, and glycosaminoglycan measurements using safranin O staining, digital densitometry, and uronic acid determination. Proteoglycan synthesis was studied by metabolic [35]sulphate labelling followed by autoradiography, and electrophoretic analysis of extracted proteoglycans. Northern analyses were performed to determine the mRNA levels of type II collagen, aggrecan, and Sox9 in cartilage samples.
Results: Radiosynovectomy had no major effect on the histological appearance of articular cartilage in mature rabbits, whereas more fibrillation was seen in [166Ho]FHMA radiosynovectomised knee joints of growing rabbits two months after treatment, but not after one year. Radiosynovectomy did not cause changes in the glycosaminoglycan content of cartilage or in the synthesis or chemical structure of proteoglycans. No radiosynovectomy related changes were seen in the mRNA levels of type II collagen, whereas a transient down regulation of aggrecan and Sox9 mRNA levels was seen in young rabbits two months after [166Ho]FHMA radiosynovectomy.
Conclusions: [166Ho]FHMA radiosynovectomy caused no obvious chondrocyte damage or osteoarthritic changes in mature rabbits, but in growing rabbits some transient radiation induced effects were seen—for example, mild cartilage fibrillation and down regulation of cartilage-specific genes.
PMCID: PMC1754287  PMID: 12480668
18.  Preparation of Colloidal Gold Immunochromatographic Strip for Detection of Paragonimiasis skrjabini 
PLoS ONE  2014;9(3):e92034.
Paragonimiasis is a food-borne trematodiasis, a serious public health issue and a neglected tropical disease. Paragonimus skrjabini is a unique species found in China. Unlike paragonimiasis westermani, it is nearly impossible to make a definitive diagnosis for paragonimiasis skrjabini by finding eggs in sputum or feces. Immunodiagnosis is the best choice to detect paragonimiasis skrjabini. There is an urgent need to develop a novel, rapid and simple immunoassay for large-scale screening patients in endemic areas.
Methodology/Principal Findings
To develop a rapid, simple immunodiagnostic assay for paragonimiasis, rabbit anti-human IgG was conjugated to colloidal gold particles and used to detect antibodies in the sera of paragonimiasis patients. The synthesis and identification of colloidal gold particles and antibody-colloidal gold conjugates were performed. The size of colloidal gold particles was examined using a transmission electron microscope (TEM). The average diameter of colloidal gold particles was 17.46 nm with a range of 14.32–21.80 nm according to the TEM images. The formation of antibody-colloidal gold conjugates was monitored by UV/Vis spectroscopy. Excretory-secretory (ES) antigen of Paragonimus skrjabini was coated on nitrocellulose membrane as the capture line. Recombinant Staphylococcus protein A was used to prepare the control line. This rapid gold immunochromatographic strip was assembled in regular sequence through different accessories sticked on PVC board. The relative sensitivity and specificity of the strip was 94.4% (51/54) and 94.1% (32/34) respectively using ELISA as the standard method. Its stability and reproducibility were quite excellent after storage of the strip at 4°C for 6 months.
Immunochromatographic strip prepared in this study can be used in a rapid one-step immunochromatographic assay, which is instantaneous and convenient.
PMCID: PMC3958401  PMID: 24643068
19.  Assessment of yttrium-90 citrate radiosynovectomy treatment with bone scintigraphy in lipoma arborescens 
A 37-year-old male patient presented with right knee pain and swelling. The patient had a 6-year history of rheumatoid arthritis. Physical examination was notable for swelling and tenderness of the right knee. The diagnosis of lipoma arborescens (LA) was confirmed from the magnetic resonance imaging of the right knee. Herein, we report the use of bone scintigraphy in a case of LA treated with yttrium-90 radiosynovectomy.
PMCID: PMC4746855  PMID: 26917908
Bone scintigraphy; lipoma arborescens; radiosynovectomy; yttrium-90
20.  Radiosynovectomy in Hemophilic Synovitis 
Radisosynovectomy (RS) is a local form of radionuclide therapy used in various forms of arthritis characterized by synovitis. In hemophilic arthropathy, RS provides removal of inflamed synovium and prevents further joint damage. This review focuses on the practical aspects of radionuclide synovectomy in hemophilic patients and describes the issues both related to the methodology and post-therapeutic follow-up.
Conflict of interest:None declared.
PMCID: PMC3957964  PMID: 24653927
radioisotope therapy; Hemophilia; synovitis
21.  Long term follow up of radiosynovectomy with yttrium-90 silicate in haemophilic haemarthrosis. 
Annals of the Rheumatic Diseases  1993;52(7):548-550.
OBJECTIVES--The aim of this study was to evaluate the long term effect of radiation synovectomy with yttrium-90 silicate in haemophiliac patients with recurrent haemarthrosis. METHODS--The bleeding frequency and the mobility of the joint were recorded in 16 joints of 14 patients 1 year before radiosynovectomy and during follow up, which ranged from 3 to 6 years. Patients evaluated the effect of their own treatment by completing a questionnaire. Radiographs of the joints were scored by an independent radiologist before treatment. RESULTS--A satisfactory reduction of the frequency of haemorrhage was achieved in 94% of joints during the first year after treatment and was maintained in 63% until the end of the follow up period. In general there was no decrease in mobility attributable to radiosynovectomy, and the patients' own evaluations agreed with the evaluations based on the frequencies of haemarthrosis in 75%. Patients who had only minor, or no, radiological abnormalities of the joints before treatment showed the best results. One patient developed synovitis as a complication of the radiosynovectomy. CONCLUSION--Radiosynovectomy is an effective and safe treatment for recurrent haemarthrosis in haemophiliac patients, especially in those who have joints with no or minor radiological damage.
PMCID: PMC1005098  PMID: 8346985
22.  Influence of Formulation and Processing Variables on Properties of Itraconazole Nanoparticles Made by Advanced Evaporative Precipitation into Aqueous Solution 
AAPS PharmSciTech  2012;13(3):949-960.
Nanoparticles, of the poorly water-soluble drug, itraconazole (ITZ), were produced by the Advanced Evaporative Precipitation into Aqueous Solution process (Advanced EPAS). This process combines emulsion templating and EPAS processing to provide improved control over the size distribution of precipitated particles. Specifically, oil-in-water emulsions containing the drug and suitable stabilizers are sprayed into a heated aqueous solution to induce precipitation of the drug in form of nanoparticles. The influence of processing parameters (temperature and volume of the heated aqueous solution; type of nozzle) and formulation aspects (stabilizer concentrations; total solid concentrations) on the size of suspended ITZ particles, as determined by laser diffraction, was investigated. Furthermore, freeze-dried ITZ nanoparticles were evaluated regarding their morphology, crystallinity, redispersibility, and dissolution behavior. Results indicate that a robust precipitation process was developed such that size distribution of dispersed nanoparticles was shown to be largely independent across the different processing and formulation parameters. Freeze-drying of colloidal dispersions resulted in micron-sized agglomerates composed of spherical, sub-300-nm particles characterized by reduced crystallinity and high ITZ potencies of up to 94% (w/w). The use of sucrose prevented particle agglomeration and resulted in powders that were readily reconstituted and reached high and sustained supersaturation levels upon dissolution in aqueous media.
PMCID: PMC3429681  PMID: 22752680
colloidal dispersion; emulsion; evaporative precipitation into aqueous solution; itraconazole; nanoparticles; poorly water-soluble drug
23.  Combined therapeutic efficacy of 188Re-liposomes and sorafenib in an experimental colorectal cancer liver metastasis model by intrasplenic injection of C26-luc murine colon cancer cells 
Molecular and Clinical Oncology  2014;2(3):380-384.
Rhenium-188 (188Re) displays abundant intermediate energy β emission and possesses a physical half-life of 16.9 h. Sorafenib is an orally available multikinase inhibitor that targets Raf kinases and vascular endothelial growth factor receptors (VEGFRs). Sorafenib has demonstrated preclinical and clinical activity against several types of tumors, such as renal cell and colorectal carcinoma. In this study, we investigated the efficacy of radiotherapeutics of 188Re-liposomes combined with sorafenib in a C26-luc metastatic colorectal liver tumour mouse model. Liver metastases were established by intrasplenic injection of C26-luc murine colon cancer cells. Based on the results of the toxicity assessment, an administration dose of 80% the maximum tolerated dose was selected. 188Re-liposomes were administered on day 1, when metastases of several hundred micrometers in diameter were observed. In the combination therapy group, 10 mg/kg sorafenib (co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar) was administered every other day for 1 week and the survival of mice was assessed. The tumor growth was more significantly inhibited in the 188Re-liposome plus sorafenib group compared with the 188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). Furthermore, 188Re-liposomes combined with sorafenib achieved higher survival rates compared with the 188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). These results support the use of combined radio-chemotherapy with 188Re-liposomes plus sorafenib as a viable treatment option in the adjuvant setting for liver metastases of colorectal cancer.
PMCID: PMC3999117  PMID: 24772304
liver metastasis; liposomes; rhenium-188; colon cancer; radiotherapy
24.  Crack formation and prevention in colloidal drops 
Scientific Reports  2015;5:13166.
Crack formation is a frequent result of residual stress release from colloidal films made by the evaporation of colloidal droplets containing nanoparticles. Crack prevention is a significant task in industrial applications such as painting and inkjet printing with colloidal nanoparticles. Here, we illustrate how colloidal drops evaporate and how crack generation is dependent on the particle size and initial volume fraction, through direct visualization of the individual colloids with confocal laser microscopy. To prevent crack formation, we suggest use of a versatile method to control the colloid-polymer interactions by mixing a nonadsorbing polymer with the colloidal suspension, which is known to drive gelation of the particles with short-range attraction. Gelation-driven crack prevention is a feasible and simple method to obtain crack-free, uniform coatings through drying-mediated assembly of colloidal nanoparticles.
PMCID: PMC4538394  PMID: 26279317
25.  Duloxetine HCl Lipid Nanoparticles: Preparation, Characterization, and Dosage Form Design 
AAPS PharmSciTech  2011;13(1):125-133.
Solid lipid nanoparticles (SLNs) of duloxetine hydrochloride (DLX) were prepared to circumvent the problems of DLX, which include acid labile nature, high first-pass metabolism, and high-dosing frequency. The DLX-SLNs were prepared by using two different techniques, viz. solvent diffusion method and ultrasound dispersion method, and evaluated for particle size, zeta potential, entrapment efficiency, physical characteristics, and chemical stability. Best results were obtained when SLNs were prepared by ultrasound dispersion method using glyceryl mono stearate as solid lipid and DLX in ratio of 1:20 and mixture of polysorbate 80 and poloxamer 188 as surfactant in concentration of 3%. The mean particle size of formulation and entrapment efficiency was 91.7 nm and 87%, respectively, and had excellent stability in acidic medium. Differential scanning calorimetry and X-ray diffraction data showed complete amorphization of DLX in lipid. In vitro drug release from SLNs was observed for 48 h and was in accordance with Higuchi kinetics. In vivo antidepressant activity was evaluated in mice by forced swim test. DLX-SLNs showed significant enhancement in antidepressant activity at 24 h when administered orally in comparison to drug solution. These results confirm the potential of SLNs in enhancing chemical stability and improving the efficacy of DLX via oral route. The SLN dispersion was converted into solid granules by adsorbing on colloidal silicon dioxide and characterized for particle size after redispersion, morphology, and flow properties. Results indicated that nanoparticles were successfully adsorbed on the carrier and released SLNs when dispersed in water.
PMCID: PMC3299448  PMID: 22167415
acid labile; adsorption; duloxetine HCl; lymphatic absorption; solid lipid nanoparticles

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