Potential Theranostic Boron Neutron Capture Therapy Agents as Multimodal Radiopharmaceuticals.

Boron neutron capture therapy (BNCT) has been extant for decades and continues to be practiced in many centers around the globe. Most of the active clinical trials utilize boronophenylalanine as the drug containing boron atoms. The important aspect that has been added to the BNCT practice is the use of an F-18 radiolabeled analog for ascertaining targeting and monitoring follow-up studies. The recent widespread application of therapeutic radiopharmaceuticals, especially peptides (somatostatin analogs), prostate-specific antigen-binding ligands, or immunomolecules, offers the ambit for invention of new tumor-specific BNCT agents, especially for BNCT-susceptible tumors, that is, locoregional cancers such as head and neck cancer. Such BNCT agents, when radiolabeled, can enable simultaneous imaging and/or therapeutic applications (depending on the radionuclide used) through multimodal approaches. Development of boron-rich moieties such as sodium borocaptate and neutral carboranes combined with tumor-targeting moieties can lead to a new horizon in BNCT. The review covers various aspects of drug design, tumor targeting, and possible future radiopharmaceutical development for multimodal theranostic application in humans.

Comparison of Serum Thyroglobulin Levels in Differentiated Thyroid Cancer Patients Using In-House Developed Radioimmunoassay and Immunoradiometric Procedures.

Thyroglobulin (Tg) is a proven tumor marker in the follow-up and post-operative management of patients with differentiated thyroid cancer (DTC). All assays for serum thyroglobulin (s-Tg) are based on immunoassays, however, the assay technique has a bearing on the variations seen in the estimations. We studied this using four in-house developed radioimmunoassays (RIA) and immunoradiometric assays (IRMA). Limit of detection, working range, recovery, dilution test, precision profiles and method comparison were evaluated. All four methods were used for the estimation of s-Tg in DTC patients and also compared for their performance using commercially available Tg IRMA kits from DiaSorin and Izotop. The s-Tg values measured by six different immunoassays showed very significant inter-method correlation (0.84-0.99, p < 0.001). However, among the in-house developed assays; the coated tube IRMA showed a better sensitivity and precision at the lower concentration range and hence, is preferable for the routine measurement of s-Tg in patients negative for Tg autoantibodies (TgAb). Although the second generation IRMAs offer practical benefits of having higher sensitivity, shorter turn-around time and convenience of automation, they, unfortunately, also have higher tendency for interference from both TgAb and heterophilic antibodies, if present in the sample. On the contrary, RIA is less prone to such interference and, hence, can be used in patients with TgAb. In order to effectively use this test, it is important that nuclear medicine physicians and endocrinologists understand these intrinsic technical limitations encountered during s-Tg measurement.

Preliminary evaluation of indigenous 90 Y-labelled microspheres for therapy of hepatocellular carcinoma.

BACKGROUND & OBJECTIVES: Yttrium-90 ( 90 Y)-based radioembolization has been employed to treat hepatocellular carcinoma (HCC) as commercial radioactive glass and polymeric resin microspheres. However, in India and other Asian countries, these preparations must be imported and are expensive, validating the need for development of indigenous alternatives. This work was aimed to develop an economically and logistically favourable indigenous alternative to imported radioembolizing agents for HCC therapy. METHODS: The preparation of 90 Y-labelled Biorex 70 microspheres was optimized and in vitro stability was assessed. Hepatic tumour model was generated in Sprague-Dawley rats by orthotopic implantation of N1S1 rat HCC cell line. In vivo localization and retention of the 90 Y-labelled Biorex 70 microspheres was assessed for seven days, and impact on N1S1 tumour growth was studied by histological examination and biochemical assays. RESULTS: Under optimal conditions, >95% 90 Y-labelling yield of Biorex70 resin microspheres was obtained, and these showed excellent in vitro stability of labelling (>95%) at seven days. In animal studies, 90 Y-labelled Biorex 70 microspheres were retained (87.72±1.56% retained in liver at 7 days). Rats administered with 90 Y-labelled Biorex 70 microspheres exhibited lower tumour to liver weight ratio, reduced serum alpha-foetoprotein level and greater damage to tumour tissue as compared to controls. INTERPRETATION & CONCLUSIONS: 90 Y-labelled Biorex 70 microspheres showed stable retention in the liver and therapeutic effect on tumour tissue, indicating the potential for further study towards clinical use.

Preparation & in vitro evaluation of 9°Y-DOTA-rituximab.

BACKGROUND & OBJECTIVES: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. METHODS: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. RESULTS: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. INTERPRETATION & CONCLUSIONS: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the radiolabelled conjugate suggesting the potential uitability of the formulation as a radiopharmaceutical for therapy of NHL.

Studies on batch formulation of a kit for the preparation of the 99mTc-Ubiquicidin (29-41): An infection imaging agent.

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 SnCl2 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).

Pharmacokinetic, Dosimetry and Toxicity Study of ¹77Lu-EDTMP in Patients: Phase 0/I study.

177Lu-EDTMP has been proposed as a potent bone pain palliation agent owing to theoretical advantage of reduced bone marrow suppression resulting from the low ß(-) energy and a suitably long half-life facilitating its wider distribution with less loss from radioactive decay. Herein, we report the pharmacokinetics, dosimetry and toxicity analysis of 177Lu-EDTMP in patients (phase-0/I study). In a phase-0 study, the biokinetics of skeletal and non-skeletal uptake of 177Lu-EDTMP was assessed in 6 patients with metastatic prostate cancer using tracer doses (172.7-206.9MBq). Data of whole skeletal uptake, blood and fractionated urine samples were obtained and dosimetric calculations were performed using the OLINDA/EXM 1.0 software. Prolonged bone retention was observed in all patients. Excretion was mainly via the renal route and blood clearance was rapid and biphasic. Mean estimated red marrow dose was 0.80±0.15mGy/MBq while mean total-body dose was 0.16±0.04mGy/MBq. A maximum tolerated dose (MTD) of 2000-3250MBqfor 177Lu-EDTMP was calculated. For the phase-I study, 21 patients with metastatic prostate cancer were given a therapeutic dose of 177Lu- EDTMP (692-5550MBq). Toxiciy (WHO), evaluated by assessment of hemoglobin levels, platelet and leukocyte counts over 12 weeks, was mainly limited to anemia or thrombocytopenia. Only transient toxicity was observed in 14/21 patients, of which 6 had baseline toxicity. Beyond the MTD, a significantly higher number of patients displayed grade 3-4 toxicity. Pain relief, assessed by VAS pain score, was observed in 86% patients with median relief duration of 7 weeks. The results demonstrate that 177Lu-EDTMP has excellent pharmacokinetic and dosimetric properties, besides being safe and effective. Along with estimating radiation dose values to certain critical organs, we have also proposed an MTD for 177Lu-EDTMP that correlated well with toxicity data. The encouraging dosimetry and toxicity data of 177Lu-EDTMP reported provide the basis for subsequent phases of the studies to establish complete effectiveness and safety of 177Lu-EDTMP as an attractive alternative to other radioactive bone pain palliation agents.

(131)I-Nimotuzumab - A potential radioimmunotherapeutic agent in treatment of tumors expressing EGFR.

The anti-EGFR antibody Nimotuzumab was radioiodinated with I-131 by Chloramine T and Iodogen methods. The (131)I-Nimotuzumab was purified and characterized by HPLC. Purified (131)I-Nimotuzumab exhibited radiochemical purity of >95% and retained good in vitro stability upto 24h at room temperature by both the methods. Cell binding studies carried out in A431 cells expressing EGF receptors showed good immunoreactivity of the product upto 5 days post radioiodination. Biodistribution studies in normal Swiss mice showed fast clearance by both renal and gastrointestinal routes with minimal thyroid uptake.

Cellular and molecular effects of beta radiation from I-131 on human tumor cells: a comparison with gamma radiation.

To study the comparative effects of beta radiation emitted from Na(131)I with equivalent dose of (60)Co γ- radiation across a range of tumor types and underlying mechanism of cytotoxicity. Different tumor cell lines of various tissue origin viz. Raji, U937, A431 and MCF-7 were irradiated with beta radiation emitted from Na(131)I and equivalent dose of (60)Co γ- radiation (0.4 Gy). Cellular toxicity and apoptosis study were carried out in four cell lines and the effects were compared. Gene expression studies of P21, RAD51 and BAX genes were analyzed by q-PCR after ß- and γ-irradiation. Cell viability (trypan blue assay) and apoptosis (DNA fragmentation and cleavage of PARP assays) studies for both types of radiation showed that among the four cell lines, A431 is most radio-resistant while MCF-7 and U937 are moderately radiation resistant and Raji cells showed maximum radiosensitivity. However, irradiation of cells with beta radiation from I-131 resulted in enhanced toxicity and apoptosis in tumor cells compared to equivalent dose of γ- rays. Gene expression studies in Raji cells showed difference in magnitude and kinetics of RAD51 and P21 expression after ß- and γ-irradiation. Our results showed higher efficacy of beta radiation in induction of tumor cell cytotoxicity and apoptosis compared to an equivalent dose of γ-radiation, which may be associated with differential DNA damage and subsequent repair kinetics in tumor cells after these radiations.

Cellular internalization and mechanism of cytotoxicity of ¹³¹I-rituximab in Raji cells.

Rituximab labeled with radioiodine (¹³¹I-rituximab) has a large potential to be employed for targeted therapy of non-Hodgkin's lymphoma. Studies of parameters such as cellular internalization, stability of ¹³¹I-rituximab bound to CD20 receptor of tumor cells, and the mechanism underlying cytotoxicity induced by ¹³¹I-rituximab will be useful for better clinical application. In this article we describe the efficacy of ¹³¹I-rituximab in CD20-expressing Raji cells. Rituximab labeled with ¹³¹I was purified on a PD-10 column and characterized using high-performance liquid chromatography and paper electrophoresis. Raji cells treated with ¹³¹I-rituximab (1.85 MBq for 2 hours) were washed then incubated. The culture medium collected from treated cells showed increased radioactivity over a longer period (>6 hours), probably due to the deiodination/degradation of ¹³¹I-rituximab. The tumor cells treated with ¹³¹I-rituximab showed time-dependent internalization of radioactivity, and at 12 hours the radioactivity was almost equally distributed in the membrane and cytoplasm. At 24 hours ~70% of the radioactivity was internalized. Cellular toxicity after ¹³¹I-rituximab treatment showed a time-dependent increase in toxicity as estimated by lactate dehydrogenase. Tumor cells treated with ¹³¹I-rituximab showed significantly higher toxicity and apoptosis compared with the those treated with the same concentration of unlabeled rituximab. The increased apoptotic death in cells treated with ¹³¹I-rituximab was associated with cleavage of poly ADP ribose polymerase and upregulation of p53 protein. This study provides a deeper understanding about the cellular internalization/stability of ¹³¹I-rituximab bound to the CD20 receptor and its efficacy in killing Raji cells.

Radiolabeling of umbilical cord-derived mesenchymal stem cells for in vivo tracking.

Non-invasive methods for the assessment of distribution, homing, and retention of stem cells are desired for the successful demonstration of stem cell therapy. Cells labeled with (99m)Tc, (18)F, and (111)In have been reported for tracking the cells in vivo. However, they can be tracked only for a limited time due to the short half lives of these isotopes. In this context, stem cells labeled with (51)Cr would be appropriate for tracking cells for a longer period of time owing to their half life of 27.7 days. Here, we have isolated mesenchymal stem cells (MSCs) from umbilical cord tissue, characterized them, and attempted to radiolabel them with (51)Cr for mapping the fate of transplanted MSC cells after an intravenous injection via the tail vein in small animals.

Studies toward the biological efficacy of (99m)Tc-labeled dextran-cysteine-mannose ([(99m)Tc(CO)(3)]DCM20) for sentinel lymph node detection.

Abstract The aim of this work was to determine the potential of (99m)Tc carbonyl-labeled dextran-cysteine-mannose (DCM20) as a mannose receptor targeting agent for sentinel lymph node (SLN) detection using biological in vitro and in vivo assays. (99m)Tc labeling of the previously reported DCM20 ligand was carried out via the [(99m)Tc(H(2)O)(3)(CO)(3)](+) synthon. High-performance liquid chromatography (HPLC) showed >99% radiolabeling yield using 50 µg of the ligand. In vitro cell uptake studies performed in RAW 264.7 mouse macrophage precursor cells showed a specific uptake of the preparation. In vivo distribution and scintigraphic imaging were studied in the Wistar rat model. Appreciable uptake and retention of the radiolabeled conjugate was observed in the SLN (4.53%±0.29% at 15 minutes and 3.35%±0.72% at 180 minutes postinjection [p.i.] for 2.5 µg/animal) with a high percentage of popliteal extraction (≥98% at all time points studied), and negligible activity in other nodes as well as blood and nontarget organs. The radiolabeled conjugate also exhibited rapid clearance from the injection site (from ~39.1% clearance at 15 minutes to ~56.5% clearance at 180 minutes p.i.), comparable to current clinically employed agents for SLN detection. These results suggest that [(99m)Tc(CO)(3)]DCM20 could be a potentially useful receptor-based SLN detection agent.

Preparation of spherical 57Co source for the calibration of intra-operative gamma probe.

This paper describes an electrochemical method for deposition of a thin layer of (57)Co on the outer surface of a copper sphere of 5mm diameter intended to be used as a point radioactive source. A description of the electrolytic cell, the process of deposition and the assay of the (57)Co activity are presented. About 1.48MBq (∼40µCi) of (57)Co could be deposited using the described method. The quality of the prepared source in terms of nonleachability, uniform distribution of activity and stability, which are necessary attributes to be ensured before application were evaluated and found to be satisfactory.

Preparation of 99mTc(CO)3-Carboxymethylthioethyl iminodiacetic acid and evaluation as a potential renal imaging agent.

UNLABELLED: The ligand, carboxymethylthioethyl iminodiacetic acid (CMT-IDA) has a suitable array of donor atoms for coordination with [99mTc(CO)3]+ core, wherein the resultant complex is expected to possess free carboxylic residues contributing towards hydrophilicity of the complex. The aim of the studies was to study the renal clearance of 99mTc(CO)3- labeled CMT-IDA and determine the potential of the complex towards its use as a renal tubular imaging agent. METHODS: CMT-IDA was radiolabeled with the [99mTc(CO)3(H2O)3]+ precursor and was characterized by reverse phase HPLC gradient elution system. Stability, hydrophilicity and plasma protein binding studies were carried out for the complex. Biodistribution studies were carried out in normal male Swiss mice at 10 min.p.i. and 2 h.p.i. The clearance was estimated from the activity observed in the urinary bladder by tying the urethra prior to injection of the complexes under study. Imaging studies were performed with male Swiss mice administered with [99mTc(CO)3(CMT-IDA)]-2 at 30 min. p.i. and blocking studies were carried out by intraperitoneal injection of probenecid 10 min. prior to the injection of the radiotracer. RESULTS: [99mTc(CO)3(CMT-IDA)]-2 could be obtained in > 98% radiochemical purity. The complex showed renal clearance of 71.0� 5.9% ID at 10 min.p.i. which increased to 84.1� 10.6% ID at 2 h.p.i., with no major activity in blood, liver, heart, lungs, stomach and spleen. However, the intestinal uptake was high (10.3� 2.0% ID) at 2 h.p.i. Scintigraphic image of the animal injected with probenecid showed an increase in the activity in kidneys indicating excretion of the [99mTc(CO)3(CMT-IDA)]-2 complex via tubular pathway. CONCLUSION: The complex, [99mTc(CO)3(CMT-IDA)]-2 has shown excellent renal clearance and thereby can be explored further for potential use as an agent towards assessing effective renal plasma flow.

An electrochemical procedure to concentrate 99mTc availed from a zirconium [99Mo] molybdate gel generator.

Successful use of electrochemical method to concentrate (99m)Tc obtained from a zirconium molybdate (Zr(99)Mo) gel generator is reported. The process consists of electrodeposition of the (99m)Tc in an oxalate bath on a small platinum electrode followed by recovery of (99m)Tc in a small volume of normal saline. The overall recovery of (99m)Tc was >90% with >99.99% radionuclidic purity and >99% radiochemical purity. The compatibility of the product in the preparation of (99m)Tc labeled formulations such as (99m)Tc-DMSA and (99m)Tc-EC was found to be satisfactory in terms of high labeling yields (>98%).

Development of a 99Mo/99mTc generator using alumina microspheres for industrial radiotracer applications.

A chromatographic (99)Mo/(99m)Tc generator for industrial applications has been developed using alumina microspheres synthesized through sol-gel process to obtain (99m)Tc in both aqueous and non-aqueous media. The sorbent was mesoporous, mechanically strong and possessed high surface area. (99m)Tc could be eluted from generator system using either acetone or 0.9% NaCl solution with appreciably high yields and high radiochemical as well as radionuclidic purity. The facile, versatile generator provides an efficient way to access (99m)Tc at industrial sites for radiotracer applications.

Studies on efficacy of a novel 177Lu-labeled porphyrin derivative in regression of tumors in mouse model.

OBJECTIVE: The aim of the present study was to develop a (177)Lu-labeled porphyrin derivative having favorable characteristics for use in targeted radiotherapy of cancer and to evaluate its biological behavior in mouse tumor models with respect to its effectiveness in tumor regression. Owing to the inherent affinity of porphyrins to accumulate in the tumors, suitably modified porphyrin derivative was chosen as the vehicle for the targeted delivery of the radionuclide. (177)Lu was preferred as the radionuclide of choice due to its suitable nuclear decay characteristics [E(ß(max)) = 497 keV, Eγ = 208 keV (11%), 113 keV (6.4%)], comparatively longer half-life (6.73 d) and ease of production in adequate quantity and sufficiently high specific activity using medium flux research reactors. METHODS: A novel porphyrin analogue, 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin was synthesized inhouse and coupled with a macrocyclic bi-functional chelating agent, namely p-amino-benzyl-1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid. The porphyrin-BFCA conjugate was labeled with (177)Lu and the biological behavior of the radiolabeled conjugate was studied by biodistribution and imaging in Swiss mice bearing either fibrosarcoma or thymic lymphoma tumors. Effectiveness of the agent in controlling the growth of tumor volumes was also studied by administering various doses of the radiolabeled preparation in the mouse tumor models. RESULTS: (177)Lu-labeled porphyrin-BFCA conjugate was prepared with high radiochemical purity ( > 99%) and adequate invitro stability. Biodistribution and imaging studies revealed good uptake and retention of the agent in the tumors with encouraging tumor to blood and tumor to muscle ratios at various post-administration time points. Tumor regression studies showed that the administration of the agent increased the average tumor doubling time and decreased the average specific growth rate substantially in both the types of tumors. However, thymic lymphoma was found to be more sensitive to the radiolabeled conjugate compared to fibrosarcoma. CONCLUSION: Preliminary biological evaluation and tumor regression studies carried out in two different tumor models in Swiss mice exhibited the promising nature of (177)Lu-labeled porphyrin-BFCA conjugate as an agent for targeted tumor therapy. However, further detailed investigations are warranted to evaluate the true potential of the developed agent.

Unusual scaling in the rheology of branched wormlike micelles formed by cetyltrimethylammonium bromide and sodium oleate.

Natural fatty acids such as sodium oleate form highly viscous supramolecular complexes with long-chain cationic surfactants through cooperative self-assembly. Here we report the rheological behavior of linear and branched wormlike micelles formed in mixtures of cetyltrimethylammonium bromide (CTAB) and sodium oleate (NaOL). Addition of sodium oleate induces an increase in the axial ratio of the mixed micelles. At a constant mole fraction of the mixture, an increase in total surfactant concentration leads to a transition from linear to branched micelles. Both linear and branched micelles impart viscoelastic behavior to the fluid, and the low-frequency data can be approximated to the Maxwell model. Scaling of the rheological parameters of CTAB-NaOL catanionic mixtures, as a function of concentration, employing dynamic rheological measurements has been determined and compared with the predictions of existing scaling laws. The structural transition from linear micelles to the branched micelles in the CTAB-NaOL micellar system greatly influences the scaling behavior of shear modulus. The scaling exponent is lower for the branched micelles compared to linear micelles, analogous to those of linear and branched polymer melts. The structural evolution is probed by light scattering and small-angle neutron scattering measurements as well.

A facile, viable approach toward the preparation of 32p patches for the treatment of skin cancer.

A facile, viable, "green" two-step, inexpensive technique was developed for the preparation of (32)P patch for the treatment of skin cancer. This technique consists of impregnation of H(3)(32)PO(4) solution into an inert solid carrier followed by immobilization into a nonleachable matrix by lamination. The morphology of the impregnated paper was evaluated by scanning electron microscope and energy-dispersive spectral analyses. Radioactive patches containing up to ∼37 MBq/cm(2) of (32)P could be prepared. Distribution of (32)P on sources was uniform and release of (32)P from the sealed source in water and saline was found to be well within the permissible levels of 185 Bq. Custom-shaped (32)P-patches after quality assurance were supplied to AIIMS, New Delhi, for clinical evaluation. (32)P-impregnated paper protected by a laminated film holds promise for treatment of superficial cancers.

Preparation of patient doses of (177)Lu-DOTA-TATE using indigenously produced (177)Lu: the Indian experience.

PURPOSE: (177)Lu (T(1/2) = 6.73 days, E(ß(max)) = 0.497 MeV, E(γ) = 113 KeV [6.4%] and 208 KeV [11%])-labeled DOTA-TATE, a somatostatin analog, is presently being considered a promising agent for the treatment of patients suffering from inoperable neuroendocrine tumors, which overexpress somatostatin receptors. The objective of the present work was to develop an optimized protocol for the preparation of therapeutic dose of (177)Lu-DOTA-TATE with as high as achievable specific activity at the time of its administration, taking into account the variable specific activity of (177)Lu available during the preparation of the agent. METHODS: (177)Lu labeling of DOTA-TATE was carried out using a precalculated amount of DOTA-TATE based on the available specific activity of (177)Lu at the time of preparation, keeping a minimum molar ratio of [DOTA-TATE]:[Lu] = 4:1, so that (177)Lu-DOTA-TATE could be obtained with highest possible specific activity without compromising its radiochemical purity and stability. RESULTS: One hundred (100) batches of (177)Lu-DOTA-TATE were prepared following this protocol till date at five different nuclear medicine centers of India, with a radiochemical purity of 98.25% ± 1.1% and specific activity of 32.74-65.49 GBq/µmol (885-1770 mCi/µmol). Till date, 250 patient doses of (177)Lu-DOTA-TATE have been dispensed and administered in 150 patients suffering from various types of neuroendocrine-originated tumors. CONCLUSIONS: The developed method ensures that patient doses of (177)Lu-DOTA-TATE could be prepared with highest possible specific activity depending upon the available specific activity of (177)Lu at the hospital radio-pharmacy.

Exploitation of nano alumina for the chromatographic separation of clinical grade 188Re from 188W: a renaissance of the 188W/188Re generator technology.

The (188)W/(188)Re generator using an acidic alumina column for chromatographic separation of (188)Re has remained the most popular procedure world over. The capacity of bulk alumina for taking up tungstate ions is limited (∼50 mg W/g) necessitating the use of very high specific activity (188)W (185-370 GBq/g), which can be produced only in very few high flux reactors available in the world. In this context, the use of high-capacity sorbents would not only mitigate the requirement of high specific activity (188)W but also facilitate easy access to (188)Re. A solid state mechanochemical approach to synthesize nanocrystalline γ-Al(2)O(3) possessing very high W-sorption capacity (500 mg W/g) was developed. The structural and other investigations of the material were carried out using X-ray diffraction (XRD), transmission electron microscopy (TEM), Brunauer Emmett Teller (BET) surface area analysis, thermogravimetric-differential thermal analysis (TG-DTA), and dynamic light scattering (DLS) techniques. The synthesized material had an average crystallite size of ∼5 nm and surface area of 252 ± 10 m(2)/g. Sorption characteristics such as distribution ratios (K(d)), capacity, breakthrough profile, and elution behavior were investigated to ensure quantitative uptake of (188)W and selective elution of (188)Re. A 11.1 GBq (300 mCi) (188)W/(188)Re generator was developed using nanocrystalline γ-Al(2)O(3), and its performance was evaluated for a period of 6 months. The overall yield of (188)Re was >80%, with >99.999% radionuclidic purity and >99% radiochemical purity. The eluted (188)Re possessed appreciably high radioactive concentration and was compatible for the preparation of (188)Re labeled radiopharmaceuticals.