Biomedical subjects

Sharmila Banerjee

Publications and source records attributed to Sharmila Banerjee.

At least 19 recordsLinked to original sources

PubMed2006

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.

Animals↗

PubMed2006

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.

Drug Stability↗

PubMed2006

Evaluation of 99mTc(CO)3 complex of 2-methyl-5-nitroimidazole as an agent for targeting tumor hypoxia.

An iminodiacetic acid (IDA) derivative of 2-methyl-5-nitroimidazole was synthesized as a carrier molecule for radiolabeling with the gamma emitting radioisotope, 99mTc, for imaging hypoxic regions of tumors. The ligand was synthesized in excellent yield and labeled using freshly prepared [99mTc(CO)3(H2O)3]+ intermediate. A complexation yield of over 95% could be achieved under mild conditions using a ligand concentration of 1 mg/mL [ approximately 3 x 10(-3)M]. The complex was characterized by HPLC and its stability in human serum was studied. Biodistribution studies performed in Swiss mice bearing fibrosarcoma tumor showed maximum accumulation in the tumor to the extent of approximately 0.52 % ID/g at 30 min post-injection (pi). The major clearance of the complex was through the hepatobiliary route. The complex showed tumor/muscle ratio of 1.75 at 30 min pi, which significantly increased to 17 at 180 min pi. However, the tumor/blood ratio was below one throughout the period of study, which could be due to slow clearance of the complex from blood.

Animals↗

PubMed2006

A novel 99mTc-labeled testosterone derivative as a potential agent for targeting androgen receptors.

With an insight that ligands possessing a N2S2 tetradentate array of donor atoms serve as ideal bifunctional chelating agents (BFCA) in the radiolabeling of target-specific agents, 5-hydroxy-3,7-diazanonan-1,9-dithiol (DAHPES) with a derivatizable substituent in the form of a hydroxyl group in the backbone was synthesized. The preparation of a steroid conjugate via coupling of this BFCA with testosterone-3-(O-carboxymethyl) oxime and the subsequent radiolabeling of the conjugate under optimized conditions with 99mTc, the ideal diagnostic radionuclide in nuclear medicine procedures, are reported. The immunoreactivity of the radiolabeled conjugate was demonstrated in a study using anti-testosterone antibodies, wherein the radiolabeled conjugate exhibited significant binding with antiserum to testosterone. Cell-uptake studies in DU145 prostate carcinoma cell line bearing androgen receptors (ARs) and comparison with AR non-bearing breast carcinoma cell line revealed the specific binding of the steroidal moiety with the testosterone receptor.

Androgen Antagonists↗

PubMed2006

175Yb-labeled hydroxyapatite: a potential agent for use in radiation synovectomy of small joints.

The preparation of 175Yb-labeled hydroxyapatite (HA) particle is described for possible use as an agent for radiation synovectomy (RS) of small-sized joints. 175Yb was produced by thermal neutron irradiation of enriched (98.6% in 174Yb) ytterbium target at a flux of approximately 3 x 10(13) n/cm(2)/s for 7 days. Specific activity of 5.5-6.0 GBq/mg and a very high radionuclidic purity to the extent of approximately 100% were obtained. In the work reported herein, HA could be labeled with 175Yb in very high radiochemical purity (>99%) using 10 mg of HA particle at pH approximately 7. The radiolabeled particulates showed excellent in vitro stability at room temperature. Serial scintigraphic images of normal as well as arthritis-bearing Wistar rats following intra-articular injection of 175Yb-HA particles in the knee joint showed complete retention of activity within the synovial cavity with no measurable activity leaching out from the joint till 144 h post-injection.

Animals↗

PubMed2006

Preparation and bioevaluation of 99mTc-carbonyl complex of 5-hydroxy tryptamine derivative.

Studies on the development of imaging agents for targeting neuroreceptors is an area of considerable interest owing to the limited availability of specific as well as selective radiolabeled agents. Therefore, with an aim of developing a receptor-specific agent, iminodiacetic acid (IDA) derivative of 5-hydroxy tryptamine viz., HTIDA has been synthesized. HTIDA could be radiolabeled with the synthon [(99m)Tc(CO)(3)(H(2)O)(3)](+) in >98% yield. The biodistribution studies in normal Swiss mice showed that the (99m)Tc(CO)(3)-HTIDA crosses the blood-brain barrier successfully with a brain uptake of 0.5%ID/g at 5min post injection. The other relevant observations from biodistribution studies included no significant uptake in any other organ and fast clearance from blood, lungs and liver.

Animals↗

PubMed2006

Preparation and in vivo evaluation of (99m)TcN-tertiary butyl xanthate as a potential myocardial agent.

(99m)Tc-tertiary butyl isonitrile (TBI), a complex structurally similar to (99m)Tc-sestamibi, has been reported to be taken up in the myocardium, albeit with significant retention in liver and lungs, thereby leading to obscure heart images when used for in vivo imaging. In the present study, tert-butyl xanthate, which is similar to TBI, but possesses two sulphur donors, has been synthesized in excellent yield by reacting tert-butanol with carbon disulphide and sodium hydroxide in dry ether. The prepared ligand was then labeled with [(99m)TcN]2+ core and the resultant complex was characterized by paper electrophoresis and HPLC. The complex was obtained in more than 95% yield and was found to be neutral. The preparation was evaluated in Swiss mice for its myocardial perfusion characteristics. The maximum heart uptake observed was 2.34%ID/g at 5 min p.i., which was cleared rapidly, with retention of 0.50%ID/g of the activity at 60 min p.i. However, owing to slow clearance from blood, liver and lungs, the heart/blood, heart/liver and heart/lung ratios at all the time points of study were not significantly high.

Animals↗

PubMed2006

Albright's hereditary osteodystrophy.

Albright's hereditary osteodystrophy is a rare inherited metabolic disorder characterized by a typical phenotype. It may be associated with or without resistance to parathyroid hormone (pseudohypoparathyroidism). Both forms may co-exist in the same family. Pseudohypoparathyroidism Type 1 and Pseudo-pseudohypoparathyroidism occur as a consequence of reduced erythrocyte membrane coupled with Gs alpha activity. We report here the variable inheritance of hormone resistance in the presence of characteristic phenotype and reduced Gs alpha activity in the same family.

Child↗

PubMed2006

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.

Animals↗

PubMed2005

Preparation and preliminary biological evaluation of a (166)Ho labeled polyazamacrocycle for possible use as an intravascular brachytherapy (IVBT) agent.

(166)Ho can be considered as a potential radionuclide for intravascular brachytherapy (IVBT) using liquid-filled balloons owing to its suitable nuclear decay characteristics. The possibility of producing (166)Ho with adequate specific activity using moderate flux reactors and natural holmium target makes it an attractive alternative of (188)Re for developing IVBT agents. Keeping in mind the high thermodynamic stability of lanthanide complexes with polyazamacrocycles, (166)Ho complex of 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA) was prepared and studied for its suitability as a possible agent for IVBT. (166)Ho was produced with adequate specific activity and high radionuclidic purity by irradiating natural Ho(2)O(3) powder. TETA was synthesized by a single step procedure using cyclam as the starting material. (166)Ho-TETA complex was prepared with excellent radiochemical purity and the complex was found to retain its stability for 7 days at room temperature. Biodistribution studies carried out in Wistar rats showed major renal clearance of the injected activity with almost no retention in any of the vital organ/tissue.

Animals↗

PubMed2005

Synthesis and evaluation of ether containing 99mTc-nitrido dithiocarbamate complexes as brain perfusion imaging agent.

In the present study, a series of (99m)Tc-nitrido dithiocarbamate complexes containing ether linkages have been prepared and their brain perfusion characteristics studied. Two primary dithiocarbamates and two secondary dithiocarbamates were synthesized in >80% yield and were characterized by elemental analyses. The ligands were then labeled using a (99m)Tc-nitrido intermediate, prepared from sodium pertechnetate using commercially available nitrido kit-vials, at a low ligand concentration of 0.1 mg. The prepared complexes were obtained in more than 95% yield and were characterized by paper electrophoresis and HPLC. All the complexes were found to be neutral and eluted out as a single species in HPLC. Biodistribution studies were carried out in normal Swiss mice. All the complexes showed uptake in the brain. (99m)TcN complexes of secondary dithiocarbamates showed higher initial brain uptake (5 min p.i.) than their primary amine counterparts. However, all the complexes exhibited rapid washout from the brain.

Animals↗

PubMed2005

99mTc-labeling of colchicine using [99mTc(CO)3(H2O)3]+ and [99mTc triple bond N]2+ core for the preparation of potential tumor-targeting agents.

Multidrug resistance (MDR) mediated by over-expression of P-glycoprotein (Pgp) is one of the major causes of failure of chemotherapy in cancer treatment. Colchicine, a naturally occurring alkaloid, is a Pgp substrate and acts as an antimitotic agent by binding to microtubules. Hence, Colchicine and its analogues radiolabeled with 99mTc may have potential for visualization of MDR in tumors. Here we report 99mTc-labeling of colchicine derivatives using [99mTc(CO)3(H2O)3]+ and [99mTc triple bond N]2+ cores. Trimethylcolchicinic acid synthesized from colchicine was used as the precursor to prepare iminodiacetic acid and dithiocarbamate derivatives which were then radiolabeled with [99mTc(CO)3(H2O)3]+ and [99mTc triple bond N]2+ cores, respectively. Radiolabeling yield for both the complexes was > 98% as observed by HPLC and TLC patterns. In vitro studies in tumor cell lines showed significant uptake for 99mTc-carbonyl as well as for 99mTc-nitrido colchicine complexes. Biodistribution studies in Swiss mice bearing fibrosarcoma tumor showed 4.1 +/- 1.2% ID/g of uptake at 30 min pi for 99mTc(CO)3-complex as against 0.42 +/- 0.24% ID/g for the 99mTcN-complex. 99mTc(CO)3-colchicine complex exhibited better pharmacokinetics with lower liver accumulation as compared to the 99mTcN-complex. Thus, colchicine radiolabeled with [99mTc(CO)3(H2O)3]+ core is more promising with respect to in vivo distribution characteristics in tumor model.

Animals↗

PubMed2005

A novel [99mTc[triple bond]N]2+ complex of metronidazole xanthate as a potential agent for targeting hypoxia.

A xanthate derivative (L) at the pendant hydroxy group of metronidazole, a nitroimidazole known to possess affinity for hypoxic tumors, has been used as the carrier molecule for targeted delivery of the gamma-emitting radioisotope 99mTc to tumors. The xanthate residues (S2(-)) from two molecules of this ligand (L) were used for chelation with the [99mTcN]2+ intermediate to form a square pyramidal and neutral [99mTcN/L2] complex in >95% yield using a low ligand concentration of 1 mg/mL (approximately 3 x 10(-3) M). Biodistribution studies carried out in Swiss mice bearing fibrosarcoma tumor showed selective accumulation of the injected activity in the tumor (1.44 +/- 0.26% per gram 1 h pi) with major clearance through hepatobiliary route. The complex showed high tumor/muscle ratio (2.15 and 3.35 at 1 and 3 h post-injection, respectively) and tumor/blood ratio, which were comparable to hypoxia targeting agents 99mTc-BMS181321 and 99mTc-BRU59-21 reported earlier.

Animals↗

PubMed2005

An estradiol-conjugate for radiolabelling with 177Lu: an attempt to prepare a radiotherapeutic agent.

177Lu is presently being considered as one of the most promising radionuclide for targeted therapy owing to its suitable decay characteristics. 177Lu in high radionuclidic purity (99.99%) and moderate specific activity (100-110 TBq/g) was produced using enriched (60.6% 176Lu) Lu2O3 target. The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is known to form stable complexes with lanthanides. Herein, we describe a novel attempt to introduce 177Lu in the estradiol moiety through a steroidal-BFCA (Bifunctional Chelating Agent) conjugate. The preparation of a steroid conjugate via coupling of 6alpha-amino-17beta-estradiol with a C-functionalized DOTA derivative viz. p-NCS-benzyl-DOTA as a BFCA and thereafter the radiolabelling of the conjugate with 177Lu is reported. Biological activity of the resultant estradiol-DOTA conjugate after radiolabelling was studied by carrying out preliminary in vitro cell uptake studies with MCF-7, human breast carcinoma cell line expressing estrogen receptors as well as binding studies with anti-estradiol antibodies.

Breast Neoplasms↗

PubMed2005

99mTcN complexes of tert-butyl dithiocarbamate and methoxyisobutyl dithiocarbamate as myocardial and brain imaging agents.

OBJECTIVE: Two ligands viz. tert-butyl dithiocarbamate (TBDTC) and methoxyisobutyl dithiocarbamate (MIBDTC), which are analogous to the tert-butyl isonitrile (TBI) and sestamibi (MIBI) ligands, were synthesized and labelled with the [99mTcN] core to evaluate their potential as myocardial agents. As these complexes have low molecular weights, and are neutral and lipophilic in nature, they have a tendency to cross the blood-brain barrier and thus deserve evaluation as potential brain perfusion imaging agents. METHODS: The dithiocarbamate ligands were synthesized from their respective amines, i.e., tert-butylamine and methoxyisobutylamine, by reacting with carbon disulfide in dry ether in the presence of crushed sodium hydroxide. The ligands were characterized by elemental analyses. The 99mTc-nitrido intermediate was prepared from 99mTcO(-)4 using commercially available nitrido kits. The complexation was carried out by mixing the freshly prepared 99mTc-nitrido intermediate and the ligand followed by incubation at room temperature for 10 min. These complexes were characterized by high-performance liquid chromatography (HPLC) using a C-18 reversed phase column with acetonitrile:water as the mobile phase, and by paper electrophoresis. Biodistribution studies were carried out in normal Swiss mice. RESULTS: The ligands were synthesized in near quantitative yields. They were radiolabelled in > 95% yields using the 99mTc-nitrido core, at low ligand concentrations of 0.01 mg . ml(-1) (5.8 x 10(-5) M) for TBDTC and 1 mg . ml(-1) (4.8 x 10(-3) M) for MIBDTC, respectively. Both the complexes were found to be neutral and eluted out as single species in HPLC. Both the complexes showed myocardial as well as brain uptake. The 99mTcN(TBDTC)2 complex showed a better heart/blood and heart/lung ratio when compared to 99mTcN(NOEt)2, an agent in phase III clinical trials proposed for myocardial imaging. This complex also showed brain uptake (3.74%ID/g) at 10 min post-injection (p.i.) with brain/blood ratios better than that of the standard agent 99mTc-D,L-HMPAO at all time points studied. 99mTcN(MIBDTC)2 showed myocardial uptake of 6.41%ID/g at 5 min p.i., which decreased to 1.76%ID/g, 60 min p.i. 99mTcN(MIBDTC)2 also showed good brain uptake (3.21%ID/g at 5 min p.i.) but relatively fast washout (1.33%ID/g at 60 min p.i.) from the target organ. CONCLUSION: Both the complexes under study showed myocardial as well as brain uptake. The results obtained with 99mTcN(TBDTC)2 shows promise towards its development as a potential brain imaging agent.

Animals↗

PubMed2004

Preparation and preliminary biological evaluation of a 177Lu labeled sanazole derivative for possible use in targeting tumor hypoxia.

The preparation of a polyazamacrocyclic-nitrotriazole conjugate for radiolabeling with the therapeutic radioisotope viz. (177)Lu is described. The nitroimidazole used for the present study is [N-2'(carboxyethyl)-2-(3'-nitro-1'-triazolyl)acetamide], the carboxylic acid derivative of sanazole, which possesses an optimal combination of desired properties such as, selective toxicity for hypoxic cells, lowered lipophilicity resulting in lowered neurotoxicity. The bifunctional chelating agent is a DOTA derivative viz. 1,4,7,10-tetraaza-1-(4'-aminobenzylacetamido)-cyclododecane-4,7,10- triacetic acid (p-amino-DOTA-anilide). (177)Lu was produced in adequate specific activity (110TBq/g) and high radionuclidic purity (approximately 100%) by irradiating enriched (60.6% (176)Lu) Lu(2)O(3) target and used for radiolabeling of the sanazole-BFCA conjugate. approximately 98% Complexation yield was achieved under optimized conditions. The complex has been characterized by paper chromatography and HPLC studies. Bioevaluation studies in Swiss mice bearing fibrosarcoma tumors revealed moderate tumor uptake (0.88%/g at 1h post-injection) with favorable tumor to blood (4.00 at 1h post-injection) and tumor to muscle (4.63 at 1h post-injection) ratios.

Animals↗

PubMed2004

175Yb labeled polyaminophosphonates as potential agents for bone pain palliation.

Ytterbium-175 (T1/2 = 4.2 d, Ebeta(max) = 480 keV) has radionuclidic properties suitable to be used in palliative therapy of bone metastases. 175Yb can be produced in moderate specific activity and good radionuclidic purity by thermal neutron bombardment of natural Yb target. The analysis of the neutron irradiated sample exhibited the presence of 96.2% 175Yb along with 2.1% 169Yb and 1.7% 177Lu at 6 h post-EOB. Four polyaminomethylene phosphonic acid ligands, ethylenediamine tetramethylene phosphonic acid, propylenediamine tetramethylene phosphonic acid, triethylenetetramine hexamethylene phosphonic acid and diethylenetriamine pentamethylene phosphonic acid were synthesized and radiolabeled with 175Yb. Complexation parameters were optimized to achieve maximum yields (92-99%). All complexes were found to retain their stability at room temperature even after 10d of preparation. Biodistribution studies of the complexes carried out in Wistar rats showed significant bone uptake (3-4.4%/g in tibia at 3h post-injection) with rapid clearance from blood and minimum uptake in soft tissues for all the complexes (bone/blood ratio approximately 40-150 and bone/muscles ratio approximately 40-400 at 3 h post-injection). These studies suggest that 175Yb complexes with the phosphonate ligands have potential for use in palliative treatment of painful bone metastases.

Animals↗

PubMed2004

177Lu-DOTA-lanreotide: a novel tracer as a targeted agent for tumor therapy.

177Lu of specific activity approximately 100-110 TBq/g and radionuclidic purity of approximately 100% was obtained by irradiation of enriched Lu2O3 (60.6% 176Lu) target for 7 days at a thermal neutron flux of 3 x 10(13)n/cm2/sec. The 177Lu labeling of a macrocyclic bifunctional chelating agent viz. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has been extensively studied. Lanreotide, [beta-naphthyl-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2] a disulfide-linked cyclic octapeptide and a somatostatin analog, reported to bind with a wide variety of tumors expressing somatostatin receptors, was conjugated with DOTA. The peptide-BFCA conjugate was characterized with the help of high-resolution two-dimensional proton NMR spectroscopy. The 177Lu labeling of the DOTA-lanreotide conjugate has been standardized to give a radiolabeling yield of 85%. The tracer showed specific binding with A-431 human epidermoid carcinoma and IMR-32 human brain neuroblastoma cells.

Cell Line, Tumor↗