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Background: Transarterial radioembolization (TARE) represents an effective targeted therapeutic option for hepatocellular carcinoma (HCC), a cancer with high mortality and poor prognosis. The aim of this study was the preparation and preliminary biological evaluation of 177 Lu-labeled polyhydroxamic acid (PHA) microparticles toward possible use in the therapy of HCC. Materials and Methods: PHA microparticles were synthesized starting from polyacrylamide. They were characterized by Fourier-transform infrared spectroscopy (FT-IR), visual color test, and laser diffraction particle size analysis. Experimental variables such as reaction pH, amount of PHA microparticles, carrier Lu content, and incubation time were optimized for maximum uptake of 177 Lu on PHA microparticles. Stability of 177 Lu-PHA microparticles was tested in the presence of competing Fe(III) ions in solution. In vitro stability of 177 Lu-PHA microparticles was evaluated in 0.05 M sodium phosphate solution (pH 7.5), saline, and serum. Bioevaluation studies were performed in normal Wistar rats by intrahepatic artery injection of the 177 Lu-PHA microparticles. Results: Successful synthesis of PHA microparticles could be confirmed from the results of FT-IR analysis and visual color test. Laser diffraction-based particle size analysis confirmed median particle size to be 54 μm, suitable for TARE. Under the optimized conditions, >99% loading of 177 Lu on PHA microparticles could be achieved. Even in the presence of high concentration of Fe(III) ions, 177 Lu binding to PHA microparticles was stable. 177 Lu-PHA microparticles exhibited excellent in vitro stability in sodium phosphate solution, saline, and serum up to 5 d at 37°C. In the bioevaluation studies performed in normal Wistar rats, 92.8% ± 3.1% of 177 Lu-PHA microparticles were retained in the liver at 96 h postinjection without any significant leakage to other organs. Conclusion: This preliminary study demonstrates the potential of synthesized PHA microparticles as carriers of therapeutic radioisotopes such as 177 Lu for treatment of HCC.

This work evaluates the potential of a 68 Ga labeled long chain 16C fatty acid for cardiac metabolic imaging. For radiolabeling with 68 Ga, hexadecanedioic acid was coupled with the chelator p-NH 2 -Bn-NOTA. Under the optimized conditions, NOTA-hexadecanoic acid could be radiolabeled with 68 Ga in ≥95% yields. In biodistribution studies carried out in Swiss mice, 68 Ga-NOTA-hexadecanoic acid showed low myocardial uptake at 2 min p.i. (3.7 ± 1.3%ID/g). While 68 Ga-NOTA-hexadecanoic acid cleared rapidly from non-target organs such as blood, lungs, intestine and kidney, wash out from liver was slow. Radio-HPLC analyses of myocardial extracts of rats injected with 68 Ga-NOTA-hexadecanoic acid confirmed its metabolic transformation in the myocardium., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This paper describes the evaluation of [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA-NCS) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) as bifunctional chelators for 177 Lu. While 177 Lu-CHX-A''-DTPA-NCS could be obtained in high yields at equimolar ratios of lutetium to CHX-A''-DTPA-NCS, >95% yield of 177 Lu-NOTA-NCS could be achieved at 1:2M ratio of lutetium to NOTA-NCS. Trace metals reduced the yields of 177 Lu-NOTA-NCS significantly as compared to 177 Lu-CHX-A''-DTPA-NCS. In vitro stability of 177 Lu-CHX-A''-DTPA-NCS was also superior to 177 Lu-NOTA-NCS. It could be concluded from this study that among the two chelators evaluated, CHX-A''-DTPA-NCS is more appropriate for preparation of 177 Lu radiopharmaceuticals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study aimed at the preparation and evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab for targeting VEGF over-expressing cancers. Bevacizumab conjugated to p-NCS-Bn-CHX-A''-DTPA was radiolabeled with (177)Lu. The radioimmunoconjugate characterized by SE-HPLC exhibited radiochemical purity of 98.0±0.6%. In vitro stability was retained upto 4 days at 37°C. In vitro cell binding studies showed good uptake by VEGF expressing U937 tumor cells. Biodistribution studies in melanoma model showed significant uptake and retention of (177)Lu-CHX-A''-DTPA-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirming its specificity to VEGF., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Preliminary work with (99m)Tc carbonyl-DTPA-Rituximab was attempted to test its feasibility as a sentinel lymph node (SLN) tracer for patients with breast cancer. (99m)Tc labeling of DTPA-Rituximab conjugate was carried out via (99m)Tc carbonyl synthon which exhibited >95% radiochemical purity and good in vitro stability. In vitro studies of (99m)Tc carbonyl-DTPA-Rituximab in normal and malignant B cells showed higher binding in malignant cells. In vivo distribution of (99m)Tc carbonyl-DTPA-Rituximab in Wistar rat footpad model indicated good retention by B-cells present in the sentinel lymph node., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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.

Objective: The objective of this study was to explore the potential of (99m)Tc carbonyl labeled DTPA-bevacizumab as a tumor imaging agent. Bevacizumab (Avastin) is a humanized monoclonal antibody (MoAb) that inhibits the vascular endothelial growth factor (VEGF)., Methods: Bevacizumab was conjugated with paraisothiocyanatobenzyl diethylenetriamine pentaacetic acid (p-SCN-Bn-DTPA) and subsequently radiolabeled with (99m)Tc via the (99m)Tc carbonyl synthon. The radioconjugate after purification was characterized by SE-HPLC and its in vitro stability was determined by histidine challenge experiments. Biodistribution studies to determine the uptake by tumors were carried out in melanoma model., Results: The radiochemical purity of (99m)Tc carbonyl labeled antibody was >98 %. The radiolabeled antibody exhibited good stability in the histidine challenge experiments up to 24 h when stored at 37 °C. Biodistribution studies in mice bearing melanoma showed significant tumor uptake (6.9 ± 2.2 % ID/g at 24 h p.i.) which was reduced to 1.6 ± 0.4 % ID/g on co-injection with cold Bevacizumab., Conclusions: The (99m)Tc carbonyl-DTPA-bevacizumab conjugate with good radiochemical purity, excellent stability and good specificity for VEGF indicates its potential as a radioimmunoscintigraphy agent for various cancers.

While [(11)C]palmitate continues to be a promising tracer for cardiovascular Positron Emission Tomography (PET) imaging, unfavourable logistics due to the short half-life of (11)C (20 min) and cumbersome labeling methodologies are the major impediments that limit its widespread use. In order to circumvent such limitations, an attempt has been made to explore the potential of (68)Ga-labeled fatty acid analogs for metabolic imaging owing to the availability of (68)Ga through a (68)Ge/(68)Ga generator on an on-demand basis. In this study, two fatty acid conjugates were synthesized by conjugation of p-SCN-benzyl NOTA with the ω-amino group of 11-amino undecanoic acid and 12-amino dodecanoic acid, respectively, under alkaline conditions. Both derivatives were radiolabeled in high yields with (68)Ga obtained from an in-house (68)Ge/(68)Ga generator. Biodistribution studies in Swiss mice showed reasonable myocardial uptake at 2 min for both derivatives (7.4 ± 2.8% ID/g for 11-carbon fatty acid-NOTA conjugate and 6.4 ± 2.1% ID/g for 12-carbon fatty acid-NOTA conjugate), which cleared rapidly over 30 min. However, significant activity was found in blood for both tracers, with heart/blood ratios observed to be below 0.5 at all time points, diminishing the potential of the synthesized complexes for cardiac imaging., (Copyright © 2014 John Wiley & Sons, Ltd.)

This article describes the preparation, quality control, and biological evaluation of (90)Y-skin patches based on Nafion(®) membrane as a viable treatment modality for superficial skin tumors such as melanoma. To arrive at the conditions for optimum uptake of (90)Y on the membrane, influence of various experimental parameters, such as pH of the feed solution, inactive yttrium carrier concentration, reaction volume, contact time, and temperature, was systematically investigated. Under the optimized conditions, >95% of the (90)Y activity (37-185 MBq) could be incorporated in the Nafion membranes to prepare (90)Y-skin patches. Quality control tests were carried out to ensure nonleachability, uniform distribution of activity, and stability of the (90)Y-patches. Mice bearing transplanted melanoma tumors that were treated with two doses of 74 MBq (90)Y-Nafion membrane sources showed complete tumor regression. Histopathological examination of the treated area showed absence of tumor. The results of the study indicate the potential of (90)Y-Nafion membrane sources for treatment of superficial skin tumors.

The anti CD20 antibody Rituximab was conjugated with para isothiocyanato benzyl diethylene triamine penta acetic acid (p-NCS-Bz-DTPA) and subsequent radiolabeling with (99m)Tc was carried out via the (99m)Tc carbonyl synthon. The (99m)Tc labeled antibody conjugate exhibited >95% radiochemical purity after purification and retained good in vitro stability when studied up to 24h at room temperature. In vitro cell binding studies carried out in Raji cells expressing CD20 antigen validated the biological efficacy of the preparation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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.

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.

Abstract Transarterial embolization by the intra-arterial administration of 131I-lipiodol is a modality used in the treatment of liver cancer. Long-chain fatty acids, being highly lipophilic, are also known to localize in the liver, thus constituting favorable vectors for this modality of treatment. Toward this, we envisaged the derivatization of 15-bromopentadecanoic acid, rendering it suitable for incorporation of a tridentate chelating moiety, for radiolabeling with the [99mTc(CO)3(H2O)3]+ precursor. The complex prepared, being lipophilic, was expected to behave as a lipiodol surrogate. The radiolabeled complex could be obtained in >95% radiochemical yield, as characterized by high-performance liquid chromatography. The intravenous injection of the radiolabeled complex in mice resulted in 23.5% +/- 4.3% uptake of injected dose (ID) organ in the liver at 3 hours postinjection. However, the uptake of the lipiodol suspension of the complex at 3 hours postinjection in the liver was found to be 43.8 +/- 13.4% ID/organ, when injected via the portal vein.

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.

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.

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.

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

Bakuchiol, extracted from the plant Psoralea corylifolia, has been proven to have anti-tumor, cytotoxic, anti-microbial and anti-inflammatory activity. In order to study if radiolabeled bakuchiol exhibits enhanced cytotoxicity, bakuchiol was radiolabeled with 125I. In-vitro uptake studies of 125I-bakuchiol were carried out using LS-A (lymphosarcoma) and barcl-95 (radiation-induced thymic lymphoma) ascitic and solid tumor cells of murine origin. In both LS-A and barcl-95, 125I-bakuchiol showed significant uptake. Viability studies showed that the radioiodinated compound showed greater cytotoxic effect than bakuchiol.

90Y-1,4,7,10-tetraazacyclododecane tetraacetic acid (90Y-DOTA) and 90Y-diethylene triamine pentaacetic acid (90Y-DTPA) complexes were studied for possible use in intra-vascular radionuclide therapy (IVRNT). 90Y was obtained from a 90Sr-90Y generator based on supported liquid membrane technique. The 90Y-DOTA and 90Y-DTPA complexes were prepared under optimised conditions. Bio-distribution of the complexes in Swiss mice showed that nearly 90% of 90Y complexes of both the ligands were excreted via urine within 1 h post-injection with negligible localisation in vital organs. Probenecid inhibition studies showed that both complexes are excreted by glomerular filtration. The predominant and quick excretion of 90Y-DOTA and 90Y-DTPA through the kidneys suggest that both these complexes could be explored for use in IVRNT.

Lanreotide, a somatostatin analogue, was radioiodinated with 125I to explore the possibility of using 123I labeled lanreotide as a diagnostic radiopharmaceutical for tumors overexpressing somatostatin (SST) receptors. Radioiodination was carried out with 125I using chloramine T as the oxidant. The labeling yield was >90%. Characterization of 125I-Lanreotide was carried out by paper electrophoresis as well as HPLC. 125I-Lanreotide was purified by chromatography using a C18 Sep-Pak column. Radiochemical purity of the purified 125I-Lanreotide thus obtained was >99%. Significant tumor uptake of 125I-Lanreotide was observed in C57BL/6 mice bearing melanoma. [ABSTRACT FROM AUTHOR]