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Broad availability and cost-effectiveness of 99Mo/99mTc generators worldwide support the use, and thus the development, of novel 99mTc-labelled radiopharmaceuticals. In recent years, preclinical and clinical developments for neuroendocrine neoplasms patient management focused on somatostatin receptor subtype 2 (SST2) antagonists, mainly due to their superiority in SST2-tumour targeting and improved diagnostic sensitivity over agonists. The goal of this work was to provide a reliable method for facile preparation of a 99mTc-labelled SST2 antagonist, [99mTc]Tc-TECANT-1, in a hospital radiopharmacy setting, suitable for a multi-centre clinical trial. To ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration, a freeze-dried three-vial kit was developed. The final composition of the kit was established based on the radiolabelling results obtained during the optimisation process, in which variables such as precursor content, pH and buffer, as well as kit formulations, were tested. Finally, the prepared GMP-grade batches met all predefined specification parameters together with long-term kit stability and stability of the product [99mTc]Tc-TECANT-1. Furthermore, the selected precursor content complies with micro-dosing, based on an extended single-dose toxicity study, where histopathology NOEL was established at 0.5 mg/kg BW, being more than 1000 times higher than the planned human dose of 20 µg. In conclusion, [99mTc]Tc-TECANT-1 is suitable to be advanced into a first-in-human clinical trial. [ABSTRACT FROM AUTHOR]

Broad availability and cost-effectiveness of 99Mo/99mTc generators worldwide support the use, and thus the development, of novel 99mTc-labelled radiopharmaceuticals. In recent years, preclinical and clinical developments for neuroendocrine neoplasms patient management focused on somatostatin receptor subtype 2 (SST2) antagonists, mainly due to their superiority in SST2-tumour targeting and improved diagnostic sensitivity over agonists. The goal of this work was to provide a reliable method for facile preparation of a 99mTc-labelled SST2 antagonist, [99mTc]Tc-TECANT-1, in a hospital radiopharmacy setting, suitable for a multi-centre clinical trial. To ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration, a freeze-dried three-vial kit was developed. The final composition of the kit was established based on the radiolabelling results obtained during the optimisation process, in which variables such as precursor content, pH and buffer, as well as kit formulations, were tested. Finally, the prepared GMP-grade batches met all predefined specification parameters together with long-term kit stability and stability of the product [99mTc]Tc-TECANT-1. Furthermore, the selected precursor content complies with micro-dosing, based on an extended single-dose toxicity study, where histopathology NOEL was established at 0.5 mg/kg BW, being more than 1000 times higher than the planned human dose of 20 µg. In conclusion, [99mTc]Tc-TECANT-1 is suitable to be advanced into a first-in-human clinical trial.

Introduction [ 99m Tc]duramycin is a SPECT tracer for cell death imaging. We evaluated the impact of kit formulation, purification and species difference on the pharmacokinetic profile and cell death targeting properties of [ 99m Tc]duramycin in order to define the optimal conditions for (pre-)clinical use. Methods Three kits were prepared (A: traditional formulation, B: containing 1/3 of ingredients, C: containing HYNIC-PEG 12 -duramycin). Following labeling, the kits were used without purification, or with SPE or HPLC purification. The pharmacokinetic profile was evaluated in mice and rats at 24 h post tracer injection (p.i.). Non-specific accumulation of [ 99m Tc]duramcyin was studied by μSPECT imaging in chemotherapy treated COLO205 tumor bearing mice pre-treated with cold duramycin (0.01–50 μg). Cell death targeting ability of the kits displaying the best pharmacokinetic profile was compared in a treatment response study in COLO205 tumor bearing mice treated with conatumumab (anti-DR5 antibody). Results HPLC purification of kit prepared [ 99m Tc]duramycin and reducing the amount of kit ingredients resulted in the best pharmacokinetic profile with low accumulation in liver, spleen and kidneys. The use of PEGylated [ 99m Tc]duramycin required longer circulation times (> 4 h pi) to obtain good imaging characteristics. Pre-treatment with duramycin significantly decreased tracer uptake in chemotherapy treated tumors in a dose-dependent manner. A blocking dose of 50 μg significantly increased non-specific accumulation in liver and spleen. Non-specific accumulation of [ 99m Tc]duramycin was however demonstrated to be species dependent. HPLC purified kit A (5.21 ± 1.71 %ID/cc) and non-purified kit B (1.68 ± 0.46 %ID/cc) demonstrated a significant increase in tumor uptake compared to baseline following conatumumab treatment. Conclusions To obtain [ 99m Tc]duramycin with favorable imaging characteristics for cell death imaging in mice [ 99m Tc]duramycin needs to be prepared with high specific activity by applying HPLC purification. The need for HPLC purification appears to be a species dependent phenomenon and might therefore not be required for clinical translation. [ABSTRACT FROM AUTHOR]

Introduction Previously, our laboratory has shown that 64 Cu-TP3805 can specifically target VPAC1 receptors and be used for positron emission tomography (PET) imaging of breast (BC) and prostate cancer (PC) in humans. Present work is aimed at the formulation of a freeze-dried diaminedithiol-peptide (N 2 S 2 -TP3805) kit and it's evaluation for the preparation of 64 Cu labeled TP3805. Parameters such as pH, temperature and incubation time were examined that influenced the radiolabeling efficiency and stability of the product. Methods Kits were prepared under different conditions and radiolabeling efficiency of TP3805 kit was evaluated for a range of pH 3.5–8.5, after addition of 64 Cu in 30 μl, 0.1 M HCl. Incubation temperature (37-90 °C) and time (30-120 min.) were also investigated. Kits were stored at −10 °C and their long term stability was determined as a function of their radiolabeling efficiency. Further, stability of 64 Cu-TP3805 complex was evaluated in presence of fetal bovine serum and bovine serum albumin by using SDS polyacrylamide gel electrophoresis. Kits were then used for PET imaging of BC and PC following eIND (101550) and institutional approvals. Specificity of 64 Cu-TP3805 for VPAC1 was examined with digital autoradiography (DAR) of prostate tissues obtained after prostatectomy, benign prostatic hyperplasia (BPH) tissue, and benign and malignant lymph nodes. Results were compared with corresponding tissue histology. Results Radiolabeling efficiency was ≥95% at final pH ~7.2 when incubated at 50 °C for 90 min. Kits were stable up to 18 months when stored at −10 °C, and 64 Cu-TP3805 complex exhibited excellent stability for up to 4 h at room temperature. 64 Cu-TP3805 complex did not show any transchelation even after 2 h incubation at 37 °C in 10% FBS as well as in BSA as determined by SDS PAGE analysis. DAR identified ≥95% of malignant lesions 11 new PC lesions, 20 high grade prostatic intraepithelial neoplasia, 2/2 ejaculatory ducts and 5/5 urethra verumontanum not previously identified The malignant lymph nodes were correctly identified by DAR and for 3/3 BPH patients, and 5/5 cysts, DAR was negative. In human BC (n = 19) and PC (n = 26) were imaged with 100% sensitivity. Conclusion Availability of ready to use N 2 S 2 -peptide kits for 64 Cu labeling is convenient and eliminates possible day to day variation during its routine preparation for clinical use. [ABSTRACT FROM AUTHOR]

Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68Ga/177Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68Ga/177Lu for 68Ga/177Lu-DOTA-TATE (M-DOTATATE). In vitro and in vivo stability of 177Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68Ga-DOTA-TATE or 177Lu-DOTA-TATE for micro-positron emission tomography and micro-singlephoton emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68Ga-DOTA-TATE and 177Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68Ga-DOTA-TATE and 177Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population. [ABSTRACT FROM AUTHOR]

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment because it is selectively expressed on the cell membrane of cancer-associated fibroblasts in most solid tumor stroma. The aim of this study was to develop a 99m Tc-labeled fibroblast activation protein inhibitor (FAPI) tracer, evaluate its imaging efficacy in nude mice, and further explore its biodistribution in healthy volunteers and uptake in tumor patients. An FAPI-derived ligand (DP-FAPI) containing d-proline was designed and synthesized as a linker, and a stable hydrophilic 99m Tc-labeled complex ([ 99m Tc]Tc-DP-FAPI) was obtained by kit formulation. In vitro cellular uptake and saturation binding assays were performed in FAP-transfected HT-1080 cells (FAP-HT-1080). The biodistribution was characterized, and micro-single-photon emission computed tomography (SPECT) imaging was performed in BALB/c nude mice bearing U87 MG tumors. Furthermore, a first-in-man application was performed in four healthy volunteers and three patients with gastrointestinal tumors. In vitro , the nanomolar K d values of [ 99m Tc]Tc-DP-FAPI indicated that it had significantly high target affinity for FAP. Biodistribution and micro-SPECT imaging studies showed that [ 99m Tc]Tc-DP-FAPI exhibited high uptake and high tumor-to-nontargeted ratios. The calculated effective dose for [ 99m Tc]Tc-DP-FAPI was approximately <5 mSv in four healthy volunteers. In three patients with gastrointestinal tumors, [ 99m Tc]Tc-DP-FAPI quantitative SPECT/CT revealed high and reliable uptake. [ 99m Tc]Tc-DP-FAPI exhibited high selectivity and affinity for FAP in vitro . The safety and effectiveness of [ 99m Tc]Tc-DP-FAPI in primary tumor imaging have been confirmed by animal and clinical studies, revealing the potential clinical application value of this tracer.

The aim of this study was to formulate an indigenous cold kit of Ubiquicidin, UBI (29-41), for easy preparation of 99m Tc-UBI (29-41) to be used as an infection imaging agent. A two component kit with the peptide and SnCl 2 as vial 1 and optimum amount of NaOH as vial 2 was successfully formulated as seen from the consistent radiochemical and pharmaceutical purity of the product over six consecutive batches of kits. The utility of the kit could be demonstrated through in-vitro and in vivo specificity of 99m Tc-UBI (29-41). [ABSTRACT FROM AUTHOR]

The cartilage-targeting strategy is based on the strong affinity of quaternary ammonium (QA) functions for cartilage proteoglycans. We use a bifunctional agent containing QA moiety and a polyazamacrocycle structure able to complex technetium-99m. 99m Tc-NTP 15-5 was selected for its high stability and its high affinity for proteoglycans in vivo . Labeling conditions of NTP 15-5 were optimized, and a lyophilized kit was developed for radiolabeling of 99m Tc-NTP 15-5 (radiochemical yields 94.6±1.8%). 99m Tc-NTP 15-5 was stable and resulted in favorable biological evaluations. [ABSTRACT FROM AUTHOR]

Introduction The scope of using no carrier added (NCA) 90 Y [T 1/2 = 64.1 h, E β(max) = 2.28 MeV] obtained from 90 Sr/ 90 Y generator in radiation synovectomy (RSV) is widely accepted. In the present study, the prospect of using 90 Y produced by (n,γ) route in a medium flux research reactor for use in RSV was explored. Methods Yttrium-90 was produced by thermal neutron irradiation of Y 2 O 3 target at a neutron flux of ~ 1 × 10 14 n/cm 2 .s for 14 d. The influence of various experimental parameters were systematically investigated and optimized to arrive at the most favorable conditions for the formulation of 90 Y labeled hydroxyapatite (HA) using HA particles of 1–10 μm size range. An optimized kit formulation strategy was developed for convenient one-step compounding of 90 Y-HA, which is easily adaptable at hospital radiopharmacy. The pre-clinical biological evaluation of 90 Y-HA particles was studied by carrying out biodistribution and bioluminiscence imaging studies in Wistar rats. The first clinical investigation using the radiolabeled preparation was performed on a patient suffering from chronic arthritis in knee joint by administering 185 MBq 90 Y-HA formulated at the hospital radiopharmacy deploying the proposed strategy. Results Yttrium-90 was produced with a specific activity of 851 ± 111 MBq/mg and radionuclidic purity of 99.95 ± 0.02%. 90 Y-labeled HA particles (185 ± 10 MBq doses) were formulated in high radiochemical purity (> 99%) and excellent in vitro stability. The preparation showed promising results in pre-clinical studies carried out in Wistar rats. The preliminary results of the first clinical investigation of 90 Y-HA preparation in a patient with rheumatoid arthritis in knee joints demonstrated the effectiveness of the formulation prepared using 90 Y produced via (n,γ) route in the management of the disease. Conclusion The studies revealed that effective utilization of 90 Y produced via (n,γ) route in a medium flux research reactor coupled with the developed strategy of using HA kits for convenient formulation of 90 Y-HA at the hospital radiopharmacy can contribute to sustainable growth in the clinical utilization of 90 Y in RSV in the foreseeable future. [ABSTRACT FROM AUTHOR]

While radiation synovectomy (RSV) constitutes a successful paradigm for the treatment of arthritis, a major cornerstone of its success resides in the selection of appropriate radiolabeled agent. Among the radionuclide used for RSV, the scope of using 177Lu [ T1/2 = 6.65 d, E β(max) = 497 keV, Eγ = 113 KeV (6.4%), 208 KeV (11%)] seemed to be attractive owing to its suitable decay characteristics, easy availability, and cost-effective production route. The present article describes a formulation of 177Lu-labeled hydroxyapatite (HA) using ready-to-use kits of HA particles of 1-10 µm size range. The developed kits enable convenient one-step preparation of 177Lu-HA (400 ± 30 MBq doses) in high radiochemical purity (>99%) and stability at hospital radiopharmacy. The preparation showed promising results in pre-clinical studies carried out in Wistar rats bearing arthritis in knee joints. In preliminary clinical investigation, significant improvement in the disease conditions was reported in 10 patients with rheumatoid arthritis of knee joints treated with 333 ± 46 MBq doses of 177Lu-HA. The studies reveal that while 177Lu labeled HA particles holds considerable promise as a cost-effective agent for RSV, the adopted strategy of using HA kits could be a potential step toward wider clinical utilization of radiolanthanide-labeled HA particles. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: 99mTc-Duramycin is a unique radiopharmaceutical that binds specifically to phosphatidylethanolamine (PE). The current effort is to develop a single-step kit formulation for the 99mTc labeling of HYNIC-Duramycin. Methods: A titration series of Tricine/TPPTS coligand systems were tested for an optimal formulation to produce 99mTc-Duramycin with high radiochemical purity and specific activity. The radiopharmaceutical prepared using the kit formulation was tested for PE binding specificity using polystyrene microbeads coated with different phospholipid species. Radiochemical performance of the kits was assessed after storage at −20°C, room temperature and 37°C. Biodistribution profile of kit-prepared 99mTc-Duramycin was characterized in healthy rats at 3, 10, 20, 60 and 180min after intravenous injection. Binding studies were performed using the rat aortic arch and a rat model of myocardial ischemia/reperfusion, which represent scenarios of physiological and pathological PE externalization. Results: A Tricine/TPPTS ratio of 10:1 led to a consistent production of 99mTc-Duramycin with high radiochemical purity (> 90%), whereas a higher ratio at 40:1 produced radiopharmaceuticals with incomplete substitution of Tricine coligand. 99mTc-Duramycin prepared using the single-step kit formulation retained PE-binding specificity. The kits are stable over long-term storage. The biodistribution profile of kit-prepared 99mTc-Duramycin is consistent with HPLC purified radiopharmaceutical from prior studies. Binding studies on a tissue level indicate that the radiopharmaceutical is suitable for studying biological processes that involve PE distribution and redistribution in various physiological and pathological conditions. Conclusion: A single-step kit formulation is developed for 99mTc-labeling of HYNIC-Duramycin. The radiopharmaceutical has high radiochemical purity and specific activity, retained PE binding activities, amiable to long-term storage, and is injection-ready for in vivo applications. [Copyright &y& Elsevier]

Abstract: Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors. Several forms of cancer, including lung, prostate, breast, and colon express receptors for bombesin-like peptides. Radiolabeled BBN analogs with a high affinity for these receptors might be used for scintigraphic imaging. Kit formulations for labeling these molecules are important for routine preparation. A freeze-dried kit for labeling HYNIC-βAla-Bombesin(7–14) with technetium-99m was prepared, and its storage stability was evaluated by in vitro and in vivo assays. [Copyright &y& Elsevier]

Abstract: Introduction: Tris(4,6-dimethoxysalicylaldimine)-N,N′-bis(3-aminopropyl)-N,N′-ethylenediamine (BAPEN), a tris(salicylaldimine) derivative, is a heart positron emission tomography (PET) agent when labeled with 68Ga. However, its labeling requires complicated and time-consuming procedures. In this study, the authors formulated a new BAPEN kit for convenient 68Ga labeling. Methods: BAPEN (0.25 mg) kits were prepared by dispensing its solution in 1 M sodium acetate buffer (pH 5.5) into sterile vials and lyophilization. The prepared kits were labeled with generator-eluted 68Ga in 0.1 N HCl. Stability in human serum was tested. Expiration date was determined by accelerated testing according to US Food and Drug Administration guidelines. A Biodistribution study was performed in normal mice after injection via tail vein. Results: The prepared kits achieved radiolabeling efficiencies in excess of 95% and showed a shelf-life of 98 days at 25°C and 64.3 months at 4°C. 68Ga-BAPEN was found to be stable in human serum at 37°C for at least 1 h. Furthermore, a biodistribution study revealed high heart uptake (10.8% ID/g, 1 h). Conclusions: The authors developed a BAPEN kit for convenient labeling with 68Ga. The 68Ga-BAPEN showed high stability and excellent biodistribution results in normal mice, which is required for myocardial PET imaging. [Copyright &y& Elsevier]

Somatostatin receptor (sstr) scintigraphy with [111In diethylenetriaminepentaacetic acid]-octreotide ([111In-DTPA]-OC) has became a routine diagnostic procedure in oncology. However, it suffers from some drawbacks concerning the limited availability, suboptimal imaging properties and elevated radiation burden of 111In. In this study synthesis, conjugation and preclinical evaluation of two new freeze-dried kit formulation based on somatostatin analogues, Tyr³-Octreotide (TOC) and Tyr³-octreotate (TATE), designed for the labeling with 99mTc are described. After cleavage from the resin and preparation of the cyclized peptides, these compounds were conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC) in solution. Radiolabeling of HYNIC peptide conjugates was performed at high specific activity using one-step kits formulation based on tricine and ethylenediamine-N,N′-diacetic acid (EDDA) as co-ligands. Both, 6-hydrazinopyridine-3-carboxylic acid0-Tyr³-Octreotide (HYNIC-TOC) and 6-hydrazinopyridine-3-carboxylic acid0-Tyr³-Octreotate (HYNIC-TATE), showed a specific and high rate of internalization after 4 h in AR4-2J rat pancreatic tumor cells, (11.2±0.8 and 18.1±1.2 respectively). Biodistribution studies in AR4-2J tumor-bearing rats showed rapid clearance of both analogues from all sstr-negative tissues except the kidneys. The specific uptake in tumor and sstr-positive tissues especially pituitary, pancreas and adrenals were observed. After 4 h the adrenals to pancreas uptake ratio for HYNIC-TOC was higher than that of HYNIC-TATE. Although both compounds had high kidney and low liver excretion, for HYNIC-TATE, it was lower. The results suggest these two new peptide based freeze-dried kits might be of great promise for clinical application in imaging of somatostatin receptor-positive tumors. [ABSTRACT FROM AUTHOR]

Minigastrin (MG) analogues specifically target cholecystokinin-2 receptors (CCK2R) expressed in different tumors and enable targeted radiotherapy of advanced and disseminated disease when radiolabeled with a beta emitter such as 177 Lu. Especially truncated MG analogues missing the penta-Glu sequence are associated with low kidney retention and seem therefore most promising for therapeutic use. Based on [d-Glu 1 ,desGlu 2-6 ]MG (MG11) we have designed the two cyclic MG analogues cyclo 1,9 [γ-d-Glu 1 ,desGlu 2-6 ,d-Lys 9 ]MG (cyclo-MG1) and cyclo 1,9 [γ-d-Glu 1 ,desGlu 2-6 ,d-Lys 9 ,Nle 11 ]MG (cyclo-MG2). In the present work we have developed and preclinically evaluated a pharmaceutical kit formulation for the labeling with 177 Lu of the two DOTA-conjugated cyclic MG analogues. The stability of the kits during storage as well as the stability of the radiolabeled peptides was investigated. A cell line stably transfected with human CCK2R and a control cell line without receptor expression were used for in vitro and in vivo studies with the radioligands prepared from kit formulations. In terms of stability 177 Lu-DOTA-cyclo-MG2 showed advantages over 177 Lu-DOTA-cyclo-MG1. Still, for both radioligands a high receptor-mediated cell uptake and favorable pharmacokinetic profile combining receptor-specific tumor uptake with low unspecific tissue uptake and low kidney retention were confirmed. Investigating the therapy efficacy and treatment toxicity in xenografted BALB/c nude mice a receptor-specific and comparable therapeutic effect could be demonstrated for both radioligands. A 1.7- to 2.6-fold increase in tumor volume doubling time was observed for receptor-positive tumors in treated versus untreated animals, which was 39-73% higher when compared to receptor-negative tumors. The treatment was connected with transient bone marrow toxicity and minor signs of kidney toxicity. All together the obtained results support further studies for the clinical translation of this new therapeutic approach.

Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68 Ga/ 177 Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68 Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68 Ga/ 177 Lu for 68 Ga/ 177 Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177 Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68 Ga-DOTA-TATE or 177 Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68 Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68 Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

While radiation synovectomy (RSV) constitutes a successful paradigm for the treatment of arthritis, a major cornerstone of its success resides in the selection of appropriate radiolabeled agent. Among the radionuclide used for RSV, the scope of using (177)Lu [T1/2  = 6.65 d, Eβ(max)  = 497 keV, Eγ  = 113 KeV (6.4%), 208 KeV (11%)] seemed to be attractive owing to its suitable decay characteristics, easy availability, and cost-effective production route. The present article describes a formulation of (177)Lu-labeled hydroxyapatite (HA) using ready-to-use kits of HA particles of 1-10 µm size range. The developed kits enable convenient one-step preparation of (177)Lu-HA (400 ± 30 MBq doses) in high radiochemical purity (>99%) and stability at hospital radiopharmacy. The preparation showed promising results in pre-clinical studies carried out in Wistar rats bearing arthritis in knee joints. In preliminary clinical investigation, significant improvement in the disease conditions was reported in 10 patients with rheumatoid arthritis of knee joints treated with 333 ± 46 MBq doses of (177)Lu-HA. The studies reveal that while (177)Lu labeled HA particles holds considerable promise as a cost-effective agent for RSV, the adopted strategy of using HA kits could be a potential step toward wider clinical utilization of radiolanthanide-labeled HA particles., (Copyright © 2014 John Wiley & Sons, Ltd.)