Evaluation of 90Y phosphate particles as a possible radiation synoviorthesis agent

BACKGROUND: 90Y is one of the radioisotopes used extensively for therapy due to its favourable nuclear characteristics. Particles and colloids incorporating 90Y are being used for radiation synovectomy, especially in European countries. METHODS: In our present work, 90Y phosphate particles were prepared and evaluated for use in radiation synovectomy. The radioactive particles were prepared by reacting carrier added 90YCl3 with phosphoric acid. RESULTS: The radiolabelling yield obtained was >95%. The particles were found to be stable in saline for up to 7 days of study at 37 degrees C. Particle size analysis of inactive yttrium phosphate showed that most of the particles were in the size range of 2-20 microm. Biodistribution studies carried out by intra-articular injection of the particles into the knee joints of rats showed that approximately 99% of the particles were retained in the joints with negligible radioactivity in the major organs even at 48 h post-injection. Scintigraphic studies in rabbit showed that >99% of the radioactive particles were retained in the knee joint even at 96 h post-injection. No significant radioactivity above background was detected in the blood. CONCLUSION: The promising results warrant further studies on 90Y phosphate particles for use in radiation synovectomy.     

Experimental radiation synovectomy in rabbit knee with holmium-166 ferric hydroxide macroaggregate

Holmium-166 ferric hydroxide macroaggregate (Ho-166 FHMA) particles possess two important properties for radiosynovectomy; relatively short half-life of the radioisotope and appropriate carrier size. Both these minimize radioactive leakage from the treated joint. This study was conducted to assess the effects of Ho-166 FHMA on synovium and synovial fluid in rabbit knee joints. Whole-knee autoradiography was utilized to determine distribution of radioactivity after intra-articular Ho-166 FHMA injection. Intra-articular injection of Ho-166 FHMA resulted in focal acute radiation necrosis in synovial lining but no hyperplasia of synoviocytes. Later, subsynovial fibrosis became evident. White blood cell and total protein levels in the joint fluid were elevated because of intra-articular inflammation due to the acute effects of radiation. Whole knee autoradiograms showed uneven distribution of the radionuclide along the synovium and extraarticular leakage on the third day after treatment.     

[Dy]Dy/Ho hydroxide macroaggregates: an in vivo generator system for radiation synovectomy

Radiation synovectomy is an effective treatment in patients suffering from inflammatory-rheumatoid and degenerative joint diseases. The aim of this work was to examine the feasibility of preparing dysprosium-166 (¹⁶⁶Dy)/holmium-166(¹⁶⁶Ho) hydroxide macroaggregates ([¹⁶⁶Dy]Dy/¹⁶⁶Ho-HM) as an in vivo generator for radiation synovectomy evaluating whether the stability of ¹⁶⁶Dy-HM and ¹⁶⁶Ho-HM complexes is maintained when the daughter ¹⁶⁶Ho is formed. The Monte Carlo (MCNP4B) theoretical depth dose profile for the in vivo [¹⁶⁶Dy]Dy/¹⁶⁶Ho generator system in a joint model was calculated and compared with that produced by ⁹⁰Y, ¹⁵³Sm and ¹⁶⁶Ho. ¹⁶⁶Dy was obtained by neutron irradiation of enriched ¹⁶⁴Dy₂O₃ in a Triga Mark III reactor. Macroaggregates were prepared by reaction of [¹⁶⁶Dy]DyCl₃ with 0.5 M NaOH in an ultrasonic bath. [¹⁶⁶Dy]Dy/¹⁶⁶Ho-HM was obtained with radiochemical purity >99.5% and with the majority of particles in the 2–5 μm range. In vitro studies demonstrated that the radio-macroaggregates are stable in saline solution and human serum without a significant change in the particle size over 14 d, suggesting that no translocation of the daughter nucleus occurs subsequent to β⁻ decay of ¹⁶⁶Dy. Biological studies in normal rats demonstrated high retention in the knee joint even 7 d after [¹⁶⁶Dy]Dy/¹⁶⁶Ho-HM administration. The Monte Carlo (MCNP4B) theoretical depth dose profiles in a joint model, showed that the in vivo [¹⁶⁶Dy]Dy/¹⁶⁶Ho generator system would produce 25% and 50% less radiation dose to the articular cartilage and bone surface, respectively, than that produced by ⁹⁰Y or pure ¹⁶⁶Ho in a treatment with the same therapeutic dose to the synovium surface. Despite that ¹⁵³Sm showed the best depth dose profile sparing doses to healthy tissues, the use of ¹⁶⁶Dy could provide the advantage of being applied in patients that cannot be reached within a few hours from a nuclear reactor and to produce less radiation exposure to the medical personnel during the radiopharmaceutical administration.     

Radiation synovectomy with 165Dy-FHMA: lymph node uptake and radiation dosimetry calculations

The lymph node uptake of 165Dy was measured in 25 patients treated by radiation synovectomy via intra-articular injection of 165Dy-ferric hydroxide macroaggregates (FHMA). An average of 0.12% of the injected dose was found in the inguinal lymph nodes 19h post injection. This results in a lymph node of 16.6 rad (166 mGy), a dose significantly less than that reported following radiation synovectomy with other radiocolloids. Dosimetry calculations for the intra-articular injection of 165Dy-FHMA are provided in the appendix.     

Radiation synovectomy revisited

Radiation synovectomy is a potential weapon in the therapeutic armamentarium of nuclear medicine. It is an attractive alternative to surgical or chemical synovectomy for the treatment of rheumatoid arthritis. In this article the clinical results obtained with radiation synovectomy from the 1950s through 1992 are summarized and reviewed. Even after taking into account the paucity of well-controlled trials and rigorous clinical follow-up, it is clear that radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis. However, the procedure is not widely used because of concerns about leakage of radioactivity from the treated joint, and the resulting high doses that can be delivered to nontarget organs. New approaches to the preparation of radiolabeled particles for use in radiation synovectomy promise to minimize this leakage and thus allow the full potential of this important radiotherapy to be realized. Correspondence to: K.F. Deutsch     

Polymeric microspheres for radionuclide synovectomy containing neutron-activated holmium-166.

Poly-L-lactic acid (PLA) microspheres containing neutron-activated 166Ho were investigated as potential agents for radionuclide synovectomy. Stable 165Ho, complexed to acetylacetone (AcAc), was incorporated into PLA spheres by the solvent evaporation technique. Spheres prepared with the optimal mean particle size of 7.2 microns (range 2-13 microns) containing 25.4% 165Ho-AcAc (9.1% 165Ho) were irradiated in a high neutron flux to produce 31.1-36.0 mCi 166Ho. In vitro human plasma studies showed that the irradiated spheres retained 99.0 +/- 0.01% of the 166Ho at 314 hr. In-vivo retention studies were conducted by administering irradiated PLA spheres with 257-591 microCi 166Ho into the joint space of normal rabbits (n = 6). Biodistribution analysis and gamma camera analysis showed 166Ho retention in the joint space after 120 hr of 97.7% +/- 0.8% and 98.2% +/- 2.4%, respectively, with no uptake by the lymph nodes. The ease with which the PLA spheres can be made in the optimal size range for later irradiation and their ability to retain the 166Ho make them attractive agents for radionuclide synovectomy.     

Preparation and evaluation of a new radiopharmaceutical for radiosynovectomy, 111Ag-labelled hydroxyapatite (HA) particles.

Many radionuclides, namely, 166Ho, 90Y, 165Dy, 32P, 198Au, 186Re, etc. have been used for radio-synovectomy. Silver-111 (T 1/2 7.45 d) can be produced in a nuclear reactor and is a potential therapeutic radionuclide decaying by beta(-) emission (92% E beta max=1.037MeV and 8% by beta(-) decay associated with emission of gamma-rays (E gamma=245.4keV, I gamma=1.33%; E gamma=342.1keV, I gamma=6.7%)). Because of the production feasibility and favourable nuclear properties, 111Ag may find use as a suitable radionuclide for radio-synovectomy. Hydroxyapatite (HA), Ca10(PO4)6(OH)2 is one of the preferred particulates for this application. In this work, [111Ag]Ag-HA particulates were successfully prepared with high-labelling yield ( approximately 97%) at various pH values. The radiochemical purity of the [111Ag]Ag-HA particles was 99.9%. Stability studies for 7 days showed that the [111Ag]Ag-HA particles retained their stability. gamma camera images at 15 min, 24h and 5 d after injection of the particles into rabbits revealed the retention of the activity in the synovial joints of the knee, thereby indicating excellent in vivo stability of [111Ag]Ag-HA particles. Therefore, [111Ag]Ag-HA particles would be a potential therapeutic agent in the management of arthritis.     

Dysprosium (165Dy) hydroxide macroaggregates for radiation synovectomy--animal studies

This paper reports the development of a new chemical formulation, Dy-HMA, to utilise the advantages of dysprosium 165 in radiation synovectomy of certain forms of arthritis. Dy-HMA is a sterile suspension of dysprosium hydroxide macroaggregates (approximately 6 mg Dy/ml) in saline with the majority of particles in the 3-5 microns range. The absence of ferric hydroxide and a higher concentration of dysprosium in the formulation offer advantages over dysprosium ferric hydroxide macroaggregates, Dy-165-FHMA. Biodistribution studies in rats and rabbits with Dy-HMA show less leakage than with Dy-FHMA and considerably less leakage than with yttrium silicate colloid. Rabbits treated with intra-articular injections of Dy-HMA equivalent to 10-30 times the typical clinical dose showed no signs of any toxic effects.     

Applied radioactivity in radiation synovectomy with [188Re]rhenium sulfide suspension

BACKGROUND: Early experience demonstrated absorbed dose in radiation synovectomy is about 100 Gy. For reaching this dose, the applied radioactivity should be calculated. METHOD: Twenty-nine synovitic models of rabbit were treated by intra-articular injection of [(188)Re]rhenium sulfide and histological changes of synovium and cartilage were examined. The applied radioactivity was calculated by method of absorbed dose factor. In clinical, eleven haemophilic patients with haemarthrosis were performed radiation synovectomy with treated [(188)Re]rhenium sulfide. The synovial thickness was evaluated by MR and its value was used to calculate the applied radioactivity. After radiation synovectomy, all patients were followed up by synovial thickness, regional inflammation, and clinical course including bleeding frequency. RESULTS: In rabbit models, the synovitic membrane can be eliminated by calculated radioactivity as planed without damaging the joint cartilage. In patients study, all patients exhibited significant reductions in synovial thickness and inflammation after radiation synovectomy with the planed radioactivities of [(188)Re]rhenium sulfide. Post-procedure bleeding frequency reduction in excellent and good reached to 63.6% by 18 months. In the cases of joint bleeding, the need for antihaemophilic factor treatment decreased immensely. Most of the recurrent episodes of bleeding were mild, subsiding with local means. CONCLUSION: The applied radioactivity in radiation synovectomy could be calculated according to thickness of inflamed synovium. Further study including comparison therapeutic results from calculated individual activities with results from fixed activities and long-term follow-up is warranted.     

Preparation and in vitro stability of (n,gamma) yttrium-90 hydroxyapatite.

Yttrium-90, produced by irradiating Y2O3 (15 mg) in the Pakistan Research Reactor (PARR-I) at a flux of approximately 1.5x10(14) neutrons/cm2/s, was used to prepare yttrium-90 hydroxyapatite particles for radiosynovectomy applications. The irradiated material was dissolved in concentrated hydrochloric acid, evaporated and taken up in distilled water. The 120 h irradiation resulted in the production of approximately 12GBq (324mCi) of 90Y at the end of irradiation (EOI) and the corresponding specific activity was approximately 1017GBq/g of yttrium. Hydroxyapatite (HA) particles were synthesized by an already reported method. Labeling of HA particles with 90Y was studied without a transchelating agent. Labeling yields of approximately 100% could be achieved with 40 mg of HA and 0.4 mg of 90Y. In vitro studies showed <2% loss of 90Y activity in normal saline and 1% human serum albumin solution over a period of 8 days. The high labeling yield, good stability and ease of preparation of the 90Y-HA particles indicate that these particles may find wide application in radiation synovectomy.     

Reduction of skeletal accumulation of radioactivity by co-injection of DTPA in [90Y-DOTA0,Tyr3]octreotide solutions containing free 90Y3+

Peptide receptor-targeted radionuclide therapy is nowadays being performed with radiolabeled DOTA-conjugated peptides, such as [90Y-DOTA0,Tyr3]octreotide (also known as OctreoTher or 90Y-DOTATOC). The incorporation of 90Y3+ is typically > or = 99%, however, since a total patient dose can be as high as 26 GBq or 700 mCi the amount of free 90Y3+ (= non-DOTA-incorporated) can be substantial. Free 90Y3+ accumulates in bone with undesired radiation of bone marrow as a consequence. 90Y-DTPA is excreted rapidly via the kidneys. Incorporation of free 90Y3+ into 90Y-DTPA might prevent this fraction from being accumulated into bone, therefore we have investigated: the biodistribution in rats of 90YCl3, [90Y-DOTA0,Tyr3]octreotide, and 90Y-DTPA; possibilities to complex 10% of free 90Y3+ in a [90Y-DOTA0,Tyr3]octreotide containing solution into 90Y-DTPA prior to intravenous injection; and effects of 10% free 90Y3+ in [90Y-DOTA0,Tyr3]octreotide solution, in the presence and in the absence of excess DTPA, on the biodistribution of in rats. The following results are presented: 90YCl3 showed high skeletal uptake (i.e., 1% ID (injected dose) per gram femur, with main localization in the epiphyseal plates) and a 24 h total body retention of 74% ID; 90Y-DTPA had rapid renal clearance, and 24 h total body retention of < 5% ID; added free 90Y3+ in [90Y-DOTA0,Tyr3]octreotide solution could rapidly be incorporated into 90Y-DTPA at room temperature; and accumulation of 90Y3+ in femur, blood, and liver was related to the amount of free 90Y3+, whereas these accumulations could be prevented by the addition of DTPA. In conclusion, the addition of excess DTPA to [90Y-DOTA0,Tyr3]octreotide with incomplete 90Y-incorporation is recommended.     

Uptake kinetics of the somatostatin receptor ligand [86Y]DOTA-DPhe1- Tyr3-octreotide ([86Y]SMT487) using positron emission tomography in non-human primates and calculation of radiation doses of the 90Y-labelled analogue

[90Y]DOTA-DPhe1-Tyr3-octreotide ([90Y]-SMT487) has been suggested as a promising radiotherapeutic agent for somatostatin receptor-expressing tumours. In order to quantify the in vivo parameters of this compound and the radiation doses delivered to healthy organs, the analogue [86Y]DOTA-DPhe1-Tyr3-octreotide was synthesised and its uptake measured in baboons using positron emission tomography (PET). [86Y]DOTA-DPhe1-Tyr3-octreotide was administered at two different peptide concentrations, namely 2 and 100 microg peptide per m2 body surface. The latter concentration corresponded to a radiotherapeutic dose. In a third protocol [86Y]DOTA-DPhe1-Tyr3-octreotide was injected in conjunction with a simultaneous infusion of an amino acid solution that was high in l-lysine in order to lower the renal uptake of radioyttrium. Quantitative whole-body PET scans were recorded to measure the uptake kinetics for kidneys, liver, lung and bone. The individual absolute uptake kinetics were used to calculate the radiation doses for [90Y]DOTA-DPhe1-Tyr3-octreotide according to the MIRD recommendations extrapolated to a 70-kg human. The highest radiation dose was received by the kidneys, with 2.1-3.3 mGy per MBq [90Y]DOTA-DPhe1-Tyr3-octreotide injected. For the 100 microg/m2 SMT487 protocol with amino acid co-infusion this dose was about 20%-40% lower than for the other two treatment protocols. The liver and the red bone marrow received doses ranging from 0.32 to 0.53 mGy and 0.03 to 0.07 mGy per MBq [90Y]DOTA-DPhe1-Tyr3-octreotide, respectively. The average effective dose equivalent amounted to 0. 23-0.32 mSv/MBq. The comparatively low estimated radiation doses to normal organs support the initiation of clinical phase I trials with [90Y]DOTA-DPhe1-Tyr3-octreotide in patients with somatostatin receptor-expressing tumours.     

Is corticosteroid coinjection necessary for radiosynoviorthesis of patients with hemophilia?

PURPOSE: Radiation synovectomy is frequently combined with intraarticular corticosteroid injection in the treatment of rheumatoid arthritis to reduce local inflammation and lymphatic clearance of radiocolloid. However, this practice is not universally accepted because corticosteroids have local and systemic toxicity such as osteonecrosis and cartilage damage and whether simultaneous corticosteroid injection together with radiocolloids is necessary in other forms of chronic synovitis like patients with hemophilia remains to be determined. MATERIALS AND METHODS: In this study, we performed radiosynoviorthesis in 14 joints of 12 patients with hemophilia with chronic knee synovitis without corticosteroid coadministration and measured radiocolloid leakage from the joint space. Five mCi Y-90 radiocolloid was injected under local anesthesia and the needle was flushed with additional lidocaine injection instead of corticosteroid. The joint was then manipulated through a full range of extension and flexion to distribute the particles homogeneously throughout the joint space. The joint was then splinted for 48 hours to minimize leakage from the joint space. After the immobilization period, radiocolloid leakage was evaluated using a gamma camera with a 20% window centered over the maximum Bremsstrahlung photopeak of Y-90. Regions of interest were drawn to the injection site on the knee joint and to the ipsilateral inguinal lymph node area. Leakage of radiocolloid was calculated by dividing the background-corrected counts/pixel at the inguinal region by the counts/pixel at the injection site. RESULTS: One of 12 patients who had knee arthroplasty was previously found to have a high amount of leakage. In this patient, 70% of radiocolloid at the injection site drained into the pelvic lymph nodes. In the remaining 11 patients, no lymph nodes were visualized in the groin area and the measured average leakage for these patients was 2.3% (range, 0-13). CONCLUSION: We concluded that in cases of appropriate particle size and strict immobilization of knee joints, leakage of radiocolloid was minimal and steroid coinjection might not be necessary for radiosynoviorthesis of patients with hemophilia with chronic knee synovitis.     

Comparison of extraarticular leakage values of radiopharmaceuticals used for radionuclide synovectomy

OBJECTIVES: Radionuclide synovectomy is a reliable therapy in patients with chronic synovitis. However, radiation doses delivered to non-target organ systems due to leakage of radioactive material from the articular cavity are an important disadvantage of this procedure. In this study we compared extraarticular leakage values of the 3 commonly used radiopharmaceuticals; 90Y-citrate, 90Y-silicate and 186Re-sulfide colloid. MATERIALS AND METHODS: Thirty-five patients with persistent synovitis were enrolled in the study. Twenty-two hemophilic, 8 rheumatoid arthritis and 5 patients with pigmented villonodular synovitis were studied. 90Y labeled silicate and citrate were used for knee joints and 186Re-sulfide for intermediate sized joints. Radiocolloid leakage values were evaluated using a gamma camera with 20% window centered over the bremsstrahlung photopeak of 90Y and a respective window over the 137 keV photopeak of 186Re. Regions of interest were drawn over the injection site, the regional lymph nodes and the background areas. Leakage of radiocolloid was calculated by dividing the counts/pixel in the regional lymph node area to the counts/pixel in the injection site. RESULTS: No visible leakage was observed. The median leakage values calculated for 90Y-citrate, 90Y-silicate and 186Re-sulfide were found as 1.9%, 2.4% and 2.7%, respectively. The difference between the variability of leakage values was not statistically significant (p > 0.05). CONCLUSION: There was no significant difference in terms of extraarticular leakage between 9Y-citrate, 9Y-silicate and 186Re-sulfide radiocolloids.     

Development of [90Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases

IntroductionBased on the concept of bifunctional radiopharmaceuticals, we have previously developed ¹⁸⁶Re-complex-conjugated bisphosphonate analogs for palliation of painful bone metastases and have demonstrated the utility of these compounds. By applying a similar concept, we hypothesized that a bone-specific directed ⁹⁰Y-labeled radiopharmaceutical could be developed.MethodsIn this study, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as the chelating site, and DOTA was conjugated with 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. [⁹⁰Y]DOTA-complex-conjugated bisphosphonate ([⁹⁰Y]DOTA-HBP) was prepared by coordination with ⁹⁰Y, and its biodistribution was studied in comparison to [⁹⁰Y]citrate.ResultsIn biodistribution experiments, [⁹⁰Y]DOTA-HBP and [⁹⁰Y]citrate rapidly accumulated and resided in the bone. Although [⁹⁰Y]citrate showed a higher level of accumulation in the bone than [⁹⁰Y]DOTA-HBP, the clearances of [⁹⁰Y]DOTA-HBP from the blood and from almost all soft tissues were much faster than those of [⁹⁰Y]citrate. As a result, the estimated absorbed dose ratios of soft tissues to osteogenic cells (target organ) of [⁹⁰Y]DOTA-HBP were lower than those of [⁹⁰Y]citrate.Conclusions[⁹⁰Y]DOTA-HBP showed superior biodistribution characteristics as a bone-seeking agent and led to a decrease in the level of unnecessary radiation compared to [⁹⁰Y]citrate. Since the DOTA ligand forms a stable complex not only with ⁹⁰Y but also with lutetium (¹⁷⁷Lu), indium (¹¹¹In), gallium (^67/68Ga), gadolinium (Gd) and so on, complexes of DOTA-conjugated bisphosphonate with various metals could be useful as agents for palliation of metastatic bone pain, bone scintigraphy and magnetic resonance imaging.     

Physico-chemical characterisation and biological evaluation of 188-Rhenium colloids for radiosynovectomy

BACKGROUND: Radiosynovectomy is a type of radiotherapy used to relieve pain and inflammation from rheumatoid arthritis. In this study, 188-Rhenium (188Re) colloids were characterized by physical and biological methodologies. This was used to assess which parameters of the kit formulation would be the basis in the development of a more effective radiopharmaceutical for synovectomy. Intraarticular injection in knees of rabbits assessed cavity leakage of activity. METHODS: The physical characteristics of tin (Sn) and sulphur (S) colloids were determined to assess the formulation with suitable properties. Particles were grouped in three ranges for analyzing their distribution according to their number, volume and surface. The ideal particle size range was considered to be from 2 to 10 microns. Membrane filtration and laser diffraction characterization methodologies were used. RESULTS: While membrane filtration could give misleading data, laser diffraction proportions more reliable results. The Sn colloid showed a better distribution of particle volume and surface than S colloid, in the 2 to 10 microns range. The 188Re-Sn colloid was obtained with a radiochemical purity higher than 95% after 30 minutes of autoclaving. While Sn colloid kit stability was verified for 60 days, the 188Re-Sn preparation was stable in the first 24 hrs. No significant intrabatch variability (n = 3) was detected. Biodistribution and scintigraphic studies in rabbits after intraarticular injection showed relevant activity only in knee, being 90% at 48 hours. CONCLUSION: The 188Re-Sn colloid is easy to prepare, is stable for 24 hours and shows minimal cavity leakage after intraarticular injection into rabbit knees, suggesting this radiotherapeutical agent has suitable physical properties for evaluation for joint treatment in humans.     

188Re radiopharmaceuticals for radiosynovectomy: evaluation and comparison of tin colloid, hydroxyapatite and tin-ferric hydroxide macroaggregates

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Development of samarium [P] phosphate colloid for radiosynoviorthesis applications: Preparation, biological and preliminary clinical studies experience

A new therapeutic radio colloid for radiosynoviorthesis (RS) applications is reported. The method of preparation involves the reaction of SmCl₃ carrier with carrier added [³²P]H₃PO₄ in the presence of gelatin. The pure colloid was recovered by dialysis purification leading to radiochemical yield of around 90%. The radiochemical purity of the pure colloid formulated in isotonic saline was over 98%, for the usage period of 14 days, as assessed by paper chromatography. Ninety percent of colloid particles were in the size of 1–10 μm as evident from the laser diffraction particle size analysis, ideally suitable for the intended end use. Animal studies revealed complete retention of the radio colloid in the rabbit knee joint. The results of clinical trials in humans are satisfactory and encouraging, satisfactory retention of the colloid in the knee joint and negligible leakage into the systemic circulation.     

Preparation and preliminary biological evaluation of 177Lu-labelled hydroxyapatite as a promising agent for radiation synovectomy of small joints

AIM: Lutetium-(177)Lu) is considered to be a promising radionuclide for use in radiation synovectomy of small-sized joints owing to its favourable decay characteristics [t(1/2)=6.73 days, E(beta)(max)=0.49 MeV, E(gamma)=113 keV (6.4%), 208 keV (11%)] and feasible and cost-effective production route. Hydroxyapatite particles are regarded as one of the most suitable carriers for applications in radiation synovectomy, and labelling with (177)Lu has been envisaged. The present work describes the preparation and preliminary biological evaluation of (177)Lu-labelled hydroxyapatite particles. METHODS: (177)Lu-labelled hydroxyapatite particles were prepared using (177)Lu produced by thermal neutron irradiation of a natural (2.6% (177)Lu) Lu(2)O(3) target and hydroxyapatite particles (particle size, 2-10 microm) prepared in-house. The biological efficacy of the radiolabelled preparation was tested by recording serial gamma scintigraphic images after injecting the agent in both normal and arthritic knee joints of Wistar rats. RESULTS: (177)Lu-hydroxyapatite was prepared with high yield and high radiochemical purity (approximately 99%) and the radiolabelled particles showed excellent in-vitro stability at room temperature. Serial scintigraphic images of normal and arthritic Wistar rats showed complete retention of activity within the synovial cavity, with no measurable activity leaching out from the joint until 168 h post-injection. CONCLUSION: Studies with (177)Lu-hydroxyapatite indicate its potential for use as an agent for radiation synovectomy of digital joints, as a viable alternative to (169)Er-based agents. The results also demonstrate the possibility of preparing a large number of patient doses of (177)Lu-hydroxyapatite from indigenously produced (177)Lu using a natural target.     

Radionuclide therapy of inflammatory joint diseases

Inflammatory joint diseases as well as arthropathy are common joint diseases. Many of them may be treated by synovectomy to stop disease progression and to improve joint function. Radiosynoviorthesis as one therapeutic procedure of rheumatoid arthritis, other inflammatory joint diseases, persistent synovial perfusion, and other joint diseases is widely used in many countries in Europe. Using Y-90 for the knee joint, Re-186 for middle sized joints and Er-169 for small joints an improvement of symptoms and function may be observed in about 60-80% of patients.