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.

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.

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.

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.

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.

Mannosylated dextran derivatives labeled with fac-[M(CO)3]+ (M = (99m)Tc, Re) for specific targeting of sentinel lymph node.

Despite being widely used in the clinical setting for sentinel lymph node detection (SLND), (99m)Tc-based colloids (e.g., (99m)Tc-human serum albumin colloids) present a set of properties that are far from ideal. Aiming to design novel compounds with improved biological properties, we describe herein the first class of fully characterized (99m)Tc(CO)3-mannosylated dextran derivatives with adequate features for SLND. Dextran derivatives, containing the same number of pendant mannose units (13) and a variable number (n) of tridentate chelators (9, n = 1; 10, n = 4, 11, n= 12), have been synthesized and fully characterized. Radiolabeled polymers of the type fac-[(99m)Tc(CO)3(k³-L)] (12, L = 9, 13, L = 10, 14, L = 11) have been obtained quantitatively in high radiochemical purity (≥ 98%) upon reaction of the dextran derivatives with fac-[(99m)Tc(CO)3(H2O)3]+. The highly stable compounds 13 and 14 were identified by comparing their HPLC chromatograms with the ones obtained for the corresponding rhenium surrogates fac-[Re(CO)3(k³-10)] (13a) and fac-[Re(CO)3(k³-11)] (14a), which have been characterized both at the chemical (NMR and IR spectroscopy, and HPLC) and physical level (DLS, AFM and LDV). Compounds 13a and 14a present a positive zeta potential (+ 7.1 mV, pH 7.4) and a hydrodynamic diameter in the range 8.4-8.7 nm. Scintigraphic imaging and biodistribution studies in Wistar rats have shown good accumulation in the sentinel node at 60 min postinjection (6.71 ± 2.35%, 13; and 7.53 ± 0.69%, 14), with significant retention up to 180 min. A clear delineation of the sentinel lymph node without significant washout to other regions was observed in the scintigraphic images. The popliteal extraction of 94.47 ± 2.45% for 14 at 1 h postinjection, as compared to 61.81 ± 2.4% for 13, indicated that 14 is a very promising compound to be further explored as SLN imaging agent.

Preparation of 166Ho-oxine-lipiodol and its preliminary bioevaluation for the potential application in therapy of liver cancer.

OBJECTIVE: Intra-arterial administration of beta-emitting radionuclides in the form of suitable radiopharmaceuticals is one of the promising modalities for the treatment of liver cancer. Ho [T1/2=26.9 h, Ebeta(max)=1.85 MeV, Egamma=81 keV (6.4%)] could be envisaged as an attractive radionuclide for the use in liver cancer therapy owing to its high-energy beta-emission, short half-life and feasibility of its production with adequately high specific activity and radionuclidic purity using moderate flux reactors. Lipiodol is chosen as the vehicle to deliver localized doses of ionizing radiation to liver cancer cells after intra-arterial hepatic infusion as it is selectively retained in the vascular periphery of the proliferating cells. METHODS: Ho was produced by thermal neutron bombardment on a natural Ho2O3 target at a flux of approximately 6 x 10 n/cm.s for 7 days. Radiolabelled lipiodol was prepared by dispersing the Ho-oxine complex in lipiodol. The biological behaviour of Ho-oxine-lipiodol was studied by biodistribution and imaging studies in normal Wistar rats. RESULTS: Ho was produced with a specific activity of 9.25-11.10 TBq/g and radionuclidic purity of approximately 100%. The Ho-labelled oxine complex was prepared in high yield (approximately 97%). Approximately, 95% of the Ho activity was dispersed in lipiodol within 30 min. The resulting radiolabelled preparation was found to exhibit good stability in physiological saline and human serum up to 3 days. The biodistribution and imaging studies revealed satisfactory hepatic retention (88.43+/-2.85% of injected activity after 2 days) with insignificant uptake in any other major organ/tissue except skeleton (6.44+/-1.07% at 2 days postinjection). CONCLUSION: The Ho-oxine-lipiodol preparation exhibited promising features in preliminary studies and warrants further investigation.

Bioevaluation of (90)Y-labeled particles in animal model of arthritis.

OBJECTIVE: The aim of the present study was to evaluate the behaviour of (90)Y-labeled particles when injected into an arthritic knee joint of Wistar rats with severe inflammation induced using Complete Freund's Adjuvant (CFA). METHODS: (90)Y-ferric hydroxide macroaggregates ((90)Y-FHMA), (90)Y-hydroxyapatite ((90)Y-HA) and (90)Y-phosphate particles ((90)YPO(4)) were prepared, subjected to quality control analyses and in vitro stability studies. Biodistribution studies were carried out by intra-articular injection into knee joints of Wistar rats induced with chronic inflammatory arthritis using CFA and by monitoring the radioactivity for retention and leakage. RESULTS: All the three preparations exhibited ~99% localization in knee joints even at 24 h p.i. with very small amounts observed in the liver and lungs, possibly due to leakage of the radiolabeled particles from the inflamed knee joint. Absence of any radioactivity in the femur indicated the in vivo stability of the particle preparations. CONCLUSIONS: The biodistribution patterns were very similar in the normal and arthritic rats and were associated with negligible leakage (up to 24 h) from the knee joint indicating the potential of all the (90)Y-radiolabeled preparations reported here, for use in radiation synoviorthesis.

Preparation and preliminary studies on 177Lu-labeled hydroxyapatite particles for possible use in the therapy of liver cancer.

INTRODUCTION: Intra-arterial administration of particulates labeled with suitable beta(-)-emitting radionuclides has emerged as one of the most successful modality for the treatment of primary and metastatic liver cancer. (177)Lu [T(1/2)=6.73 d, E(beta)(max)=0.49 MeV, E(gamma)=208 keV (11%)] could be envisaged as a viable radionuclide for use in liver cancer therapy with wider acceptability owing to its feasibility of production in large-scale and relatively longer half-life providing logistic advantages. Hydroxyapatite (HA) particles of 20-60 microm size range are chosen as the particulate carrier due to its excellent biocompatibility and ease of labeling with lanthanides. METHODS: (177)Lu was produced by thermal neutron bombardment on enriched Lu target. HA particles of desired size range were synthesized and characterized. Radiolabeling of HA particles was achieved at room temperatures within 30 min. The biological behavior of (177)Lu-labeled HA particles prepared under optimized conditions was tested in Wistar rats. RESULTS: (177)Lu was produced with a specific activity of 444.2+/-41.8 GBq/mg and radionuclidic purity of 99.98%. (177)Lu-HA was prepared with high radiochemical purity of >99%, and the radiolabeled agent showed excellent in vitro stability. The agent exhibited approximately 73% retention of injected activity in liver after 14 days postadministration with insignificant uptake in any other major organ/tissue except skeleton in biodistribution and imaging studies. CONCLUSION: (177)Lu-HA exhibited promising features in radiochemical studies. However, preliminary biodistribution studies in normal Wistar rats exhibited suboptimum liver retention and an undesirable skeletal uptake.

Development of an electrochemical 90 Sr-90 Y generator for separation of 90 Y suitable for targeted therapy.

UNLABELLED: 90 Y of high specific activity and very high radionuclidic purity (>99.998%) is essential for targeted therapy. Since the current methods used for the preparation of 90 Y from 90 Sr are not adaptable for use in a central/hospital radiopharmacy, a simple 90 Sr-90 Y generator system based on electrochemical separation technique was developed. METHODS: Two-cycle electrolysis procedure was developed for separation of 90 Y from 90 Sr in nitrate solution. The first electrolysis was performed for 90 min in 90 Sr(NO3)2 feed solution at pH 2-3 at a potential of -2.5 V with 100-200 mA current using platinum electrodes. The second electrolysis was performed for 45 min in 3 mM HNO3 at a potential of -2.5 V with 100 mA current. In this step, the cathode from the first electrolysis containing 90 Y was used as anode along with a fresh circular platinum electrode as cathode. The 90 Y deposited on the circular cathode after the second electrolysis was dissolved in acetate buffer to obtain 90 Y acetate, suitable for radiolabeling. RESULTS: >96% recovery of 90 Y could be achieved in each cycle, with an overall decay corrected yield of >90%. The recovered 90 Y had high radionuclidic purity with barely 30.2+/-15.2 kBq (817+/-411 nCi) of 90 Sr per 37 GBq (1 Ci) of 90 Y (0.817+/-0.411 ppm). Consistent and repeated separation could be demonstrated using up to 1.85 GBq (50 mCi) of 90 Sr. The generator was named "Kamadhenu," the eternally milk-yielding Indian mythological cow. CONCLUSIONS: A technique suitable for adaptation at central radiopharmacies for obtaining therapeutic quantities of pure 90 Y has been developed.

On the isolation and evaluation of a novel unsubstituted 5-nitroimidazole derivative as an agent to target tumor hypoxia.

The presence and extent of hypoxic regions in cancerous tissue bears a negative influence on the effectiveness of radiation therapy and chemotherapy of the cancer hence estimation of hypoxia is an important problem. Several (99m)Tc-labeled nitroimidazole-based non-invasive agents have been tried for this purpose but none had optimal characteristics and the search continues. Herein we report, for the first time to the best of our knowledge, the isolation, (99m)Tc(CO)(3) labeling and evaluation of an unsubstituted 5-nitroimidazole derivative obtained as a side product during the synthesis of 4-nitroimidazole derivative. The (99m)Tc(CO)(3)-labeled complex of 5-nitroimidazole derivative could be prepared in excellent yield under mild conditions. Its evaluation in fibrosarcoma tumor bearing Swiss mice showed uptake and slow clearance of injected activity from tumor. The tumor-to-muscle ratio was found to be very high but tumor-to-blood ratio greater than 1 could not be obtained throughout the limited time point study. The study revealed that complex under investigation has features similar to other 2-nitroimidazole complexes so far as the retention of injected activity in tumor is concerned.

Synthesis and bio-evaluation of a new fatty acid derivative for myocardial imaging.

Development of a (99m)Tc-fatty acid analogue is of interest, as (99m)Tc is logistically advantageous over the cyclotron-produced (11)C and (123)I. Synthesis of a 16 carbon fatty acid derivative and its radiolabeling with the novel [(99m)TcN(PNP)](2+) core is described here. Hexadecanedioic acid was conjugated to cysteine in an overall yield of 55%. This ligand could be labeled with (99m)Tc via the [(99m)TcN(PNP)](2+) core, in 80% yield, as a mixture of two isomers (syn and anti). The major isomer isolated by HPLC was used for bioevaluation studies in swiss mice and compared with radioiodinated iodophenyl pentadecanoic acid (IPPA), an established agent for myocardial metabolic imaging. (99m)Tc-labeled complex cleared faster from the non-target organs, namely, liver, lungs, and blood compared to that of [(125)I]-IPPA. However, the complex exhibited lower uptake and faster washout from the myocardium as compared to [(125)I]-IPPA.

Synthesis of 99mTc-nitrido heterocomplex of piperidine and in vitro and in vivo evaluation of its affinity for sigma receptors.

Sigma receptors are overexpressed in various types of cancer cells, making ligands that bind to these receptors attractive vectors for targeting radiation to specific sites for the imaging and therapy of oncologic disorders. In this paper, we report the synthesis of a dithiocarbamate derivative of 4-amino-N-benzylpiperidine and its radiolabeling with the [(99m)TcN(PNP)](2+) metal synthon. The radiolabeled tracer has been evaluated for sigma-receptor specificity. The radiochemical purity of the (99m)Tc-complex was >98%. The in vitro cell-binding and competition studies of the complex showed affinity and specificity toward fibrosarcoma and melanoma cells. In vivo studies carried out in mice bearing melanoma and fibrosarcoma tumors showed tumor uptakes of 1% and 1.9%, respectively, at 3 hours postinjection. In vivo blocking studies were carried out, using (+)-pentazocine, a sigma-receptor-specific agent where approximately 40% decrease in the tumor uptake was observed. The affinity of [(99m)TcN(PNP)Pip-DTC](+) complex for sigma-receptor sites ascertained through in vitro and in vivo studies makes it a potential agent for further investigation.

Polymer embedded nanocrystalline titania sorbent for 99Mo-99mTc generator.

A new sorbent material, polymer embedded nano crystalline titania (Titanium Polymer-TiP) has been developed, from titanium (IV) chloride and isopropyl alcohol, for the adsorption of 99Mo, which is a precursor to 99mTc, a workhorse in radio-pharmaceuticals. The infrared absorption spectra of the TiP showed peaks corresponding to Ti-O groups. X-ray diffraction pattern of the adsorbent corresponded to rutile TiO2. The surface area of this polymer was 30 m2/g with an average pore size of 40 nm. The average crystallite size of TiO2, embedded in polymer, was found to be 5 nm. TEM micrograph of the adsorbent revealed the network of polymer with dispersed titania phase. Potential of this adsorbent for the preparation of 99Mo-99mTc generator has been explored. 99Mo could be adsorbed on to the adsorbent column containing TiP at pH 1 from which 99mTC could be eluted with normal (0.9%) saline solution with an elution yield of approximately 80%. The quality of the 99mTcO4 obtained was in accordance with the international specifications applicable for radiopharmaceutical use. A process demonstration run was carried out with 1.1 GBq (30 mCi) 99Mo activity level making use of the above adsorbent and consistent results were obtained over a period of one week, which is generally the shelf life of 99MO-99mTC generator.

Bioevaluation studies of 32P incorporated mould brachytherapy sources for potential application in treatment of superficial tumors.

AIM: To prepare 32P-based user-friendly mould brachytherpy sources for the treatment of superficial tumors. METHODS: 32P as orthophosphoric acid was adsorbed on 15-25 mm (diameter) circular sheets of cellulose-based adsorbent paper to prepare sources containing approximately 37-74 MBq of 32P per cm of strip. The sources were immobilized between plastic sheets of 40 microm thickness. Autoradiography studies were carried out to determine the uniformity of 32P deposition in the source. Dosimetric evaluation of the sources was also carried out. Bioevaluation studies were carried out in C57BL6 mice bearing melanoma using 37-74 MBq sources. RESULTS: Cellulose-based sources containing 37-74 MBq of 32P per cm2 could be prepared from which no radioactivity leakage could be detected in water or saline. Autoradiography studies revealed 32P to be uniformly distributed in these sources. Dosimetric evaluation showed that the contact dose imparted was 10 Gy/h, sufficient for treatment of superficial tumors. In mice bearing melanoma, complete tumor regression could be achieved with two applications of 37-74 MBq sources, at an interval of 3 days. Histopathological examination of the skin tissue from the treated area proved the absence of tumor as compared with the controls. CONCLUSION: Preparation of P sources of various shapes and sizes (based on the tumor size) having uniform 32P activity distribution could be achieved. Efficacy of these sources in treating melanoma tumors could be established in the animal model.

Comparative studies of 177Lu-EDTMP and 177Lu-DOTMP as potential agents for palliative radiotherapy of bone metastasis.

(177)Lu is presently considered as an excellent radionuclide for developing bone pain palliation agents owing to its suitable nuclear decay characteristics [T(1/2)=6.73d, E(beta)((max))=497keV, E(gamma)=113keV (6.4%) and 208keV (11%)] and large-scale production feasibility with adequate specific activity using moderate flux research reactors. Multidentate polyaminophosphonic acids have already been proven as the carrier molecule of choice for radiolanthanides and similar +3 metal ions in designing agents for palliative radiotherapy of bone pain due to skeletal metastases. The present paper describes a comparison between (177)Lu complexes of two potential polyaminophosphonic acid ligands, namely Ethylenediaminetetramethylene phosphonic acid (EDTMP) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) with respect to their radiochemical and in-vivo biological characteristics. Although both the agents have exhibited promising features, the study reveals that (177)Lu-EDTMP has marginally higher skeletal accumulation in comparison to that of (177)Lu-DOTMP, while the latter has slightly faster blood clearance along with lower retention in liver and kidneys in animal models.

Extremity dosimetry for radiation workers handling unsealed radionuclides in nuclear medicine departments in India.

In India, for the past five decades, whole body radiation dose of radiation workers has been monitored by means of film and thermoluminescent dosimeter (TLD) badges worn on the body. However, there are no provision/regulatory requirements to monitor doses received at the extremities, i.e., to fingers. Finger dose monitoring is essential for controlling the extremity dose limits for occupational personnel handling unsealed radioactive sources. In order to estimate the doses received in various types of procedures using unsealed sources, finger dose monitoring was carried out in 54 major institutions in the country using a specially designed plastic finger ring embedded with a TLD. The maximum finger dose of occupational workers involved in handling Tc in such activities as extraction and radiopharmacy work is 0.35 mSv GBq; during injection of radiopharmaceuticals and scintigraphy, the doses were observed to be 1 and 0.95 mSv GBq, respectively. Similarly, while handling F-FDG, the maximum doses received during dispensing, injection, and scintigraphy were 0.098, 0.324, and 0.56 mSv GBq, respectively. The maximum radiation dose received during Re/Re balloon angioplasty and while handling Sm was 3.92 and 6.5 mSv GBq, respectively. All the doses recorded were well within the prescribed limit. However, monitoring of these doses periodically would help in compiling the feedback regarding the work practices followed in institutions handling radioisotopes in the country and would also help in maintaining a record of safe work procedures while handling radioisotopes.

On the preparation of a therapeutic dose of 177Lu-labeled DOTA-TATE using indigenously produced 177Lu in medium flux reactor.

177Lu could be produced with a specific activity of approximately 23,000 mCi/mg (850GBq/mg) by neutron activation using enriched 176Lu (64.3%) target when irradiation was carried out at a thermal neutron flux of 1 x 10(14) n/cm(2)/s for 21 d. 177Lu-DOTA-TATE could be prepared in high radiochemical yield (approximately 99%) and adequate stability using the 177Lu produced indigenously. The average level of radionuclidic impurity burden in 177Lu due to 177mLu was found to be 250 nCi of 177mLu/1 mCi of 177Lu (9.25 kBq/37 MBq) at the end of bombardment, which corresponds to 0.025% of the total activity produced. The maximum specific activity achievable via careful optimization of the irradiation parameters was found to be adequate for the preparation of a therapeutic dose of the radiopharmaceutical. The in-house preparation of this agent using 25 microg (17.41 nmole) of DOTA-TATE and indigenously produced 177Lu (0.8 microg, 4.52 nmole), corresponding to peptide/Lu ratio of 3.85 yielded 98.7% complexation. Allowing possibility of decay due to transportation to users, it has been possible to demonstrate that at our end, a single patient dose of 150-200 mCi (5.55-7.40 GBq) can be prepared by using 250-333 microg of DOTA-TATE conjugate. This amount compares well with 177Lu-DOTA-TATE prepared for a typical peptide receptor radionuclide therapy (PRRT) procedure which makes use of 100 microg of the DOTA-TATE conjugate, which incorporates 50 mCi (1.85 GBq) of 177Lu activity, thereby implying that in order to achieve a single patient dose of 150-200 mCi (5.55-7.40 GBq), 300-400 microg of the conjugate needs to be used.

Preparation and biological studies of 125I-DOTA-TATE.

DOTA-TATE, a somatostatin analog was radiolabeled with (125)I in good yields and high radiochemical purity. The product exhibited good stability in vitro. Pharmacokinetic studies in normal Swiss mice showed rapid blood clearance with low thyroid uptake. Biodistribution studies in murine melanoma showed 3.0+/-1.3% ID/g uptake in tumor at 3h post injection (p.i.), with negligible reduction at 24h p.i. Inhibition studies carried out in vivo using cold DOTA-TATE confirmed the tumor specificity of the product.

99mTc(CO)3-VIP analogues: preparation and evaluation as tumor imaging agent.

Vasoactive intestinal peptide (VIP) receptors are expressed abundantly on many types of tumors and, hence, radiolabeled VIP analogues are being explored for tumor imaging and therapy. Here, we report synthesis of three VIP analogues and their radiolabeling with (99m)Tc via a novel tricarbonyl synthon. The radiolabeled product could be prepared in high yields (>95%) and stability. In vitro studies showed significant uptake of (99m)Tc(CO)((3))-VP05 in human colon carcinoma cells. Biodistribution studies in animal tumor model showed 0.4-1%ID/g tumor uptake.