68Ga-Labeled Trastuzumab Fragments for ImmunoPET Imaging of Human Epidermal Growth Factor Receptor 2 Expression in Solid Cancers.

Background: Trastuzumab, the first humanized antibody approved for therapeutic use has shown promising results for the treatment of patients with human epidermal growth factor receptor 2 (HER2) positive cancers. The aim of this study was to formulate immunoPET agents based on trastuzumab fragments and demonstrate their potential for early diagnosis of HER2-positive tumors. Materials and Methods: F(ab')2 and F(ab') fragments of trastuzumab were prepared by enzymatic digestion and conjugated with chelator NOTA for labeling with 68Ga. For comparison, intact trastuzumab was also radiolabeled. In vitro stability, immunoreactivity, and binding affinity of radio formulations toward HER2 receptors were evaluated by performing in vitro studies in cancer cell lines. Biodistribution and PET imaging studies were performed in animal model bearing tumors. Results: 68Ga-NOTA-F(ab')-trastuzumab, 68Ga-NOTA-F(ab')2-trastuzumab, and 68Ga-NOTA-trastuzumab could be prepared with >98% radiochemical purity (% RCP) and were found to be stable when studied up to 4 h. In vitro binding studies revealed high affinity and specificity of formulations toward HER2 receptors. Specific tumor uptake of 68Ga-NOTA-F(ab')-trastuzumab and 68Ga-NOTA-F(ab')2-trastuzumab in HER2-positive tumors was observed in biodistribution and PET imaging studies. Conclusions: This study describes optimization of protocol for the formulation of 68Ga-NOTA-F(ab')-trastuzumab and 68Ga-NOTA-F(ab')2-trastuzumab for targeting HER2-overexpressing tumors. Further studies with these radioformulations are warranted to confirm their potential as immunoPET agents for management of HER2-positive breast and other solid tumors.

Effects of COVID-19 lockdown on water quality, microbial extracellular enzyme activity, and sediment-P release in the Ganga River, India.

This study investigates possible improvement in water quality and ecosystem functions in the Ganga River as influenced by COVID-19 lockdown in India. A total of 132 samples were collected during summer-2020 low flow (coinciding COVID-19 lockdown) for water (sub-surface and sediment-water interface) and 132 samples separately for sediment (river bottom and land-water interface) considering 518-km main river stem including three-point sources (one releases urban sewage and the other two add metal-rich industrial effluents) and a pollution-impacted tributary. Parameters such as dissolved oxygen deficit and the concentrations of carbon, nutrients (N and P), and heavy metals were measured in water. Sediment P-release was measured in bottom sediment whereas extracellular enzymes (EE; alkaline phosphatase, FDAase, protease, and ß-D-glucosidase) and CO2 emission were measured at land-water interface to evaluate changes in water quality and ecosystem functions. The data comparisons were made with preceding year (2019) measurements. Sediment-P release and the concentrations of carbon, nutrients, and heavy metals declined significantly (p<0.05) in 2020 compared to those recorded in 2019. Unlike the preceding year, we did not observe benthic hypoxia (DO <2.0 mg L-1) in 2020 even at the most polluted site. The EE activities, which declined sharply in the year 2019, showed improvement during the 2020. The stability coefficient and correlative evidences also showed a large improvement in the water quality and functional variables. Positive changes in functional attributes indicated a transient recovery when human perturbations withdrawn. The study suggests that timing the ecosystem recovery windows, as observed here, may help taking management decision to design mitigation actions for rivers to recover from anthropogenic perturbations.

A Facile Strategy for Preparation of Yttrium-90 Therapeutic Sources for Radionuclide Therapy.

Background: Mold brachytherapy using high-energy ß--emitting radioisotopes is a promising treatment modality for skin cancers and keloids. Simple methodologies for consistent and stable incorporation of radionuclides into the matrix are desired for preparation of therapeutic sources. Methods: The authors report a facile strategy for the stable incorporation of Yttrium-90 (90Y) into amidoxime-functionalized polyacrylonitrile-polyvinylidene fluoride (PAN-PVDF) membranes. The strategy consisted of surface modification of PAN-PVDF membranes by reaction with hydroxylamine, characterization of the functionalized membranes, and optimization of experimental variables for maximum loading of 90Y onto the membranes. Quality control tests essential for confirming the suitability of the 90Y therapeutic sources for human application, such as uniformity of activity distribution, absence of leaching of activity, and estimation of surface contamination, were performed. Theoretical calculations to estimate the dose imparted by the 90Y therapeutic sources at varying depths of tissue were also carried out to predict the possible therapeutic outcome of treatment. Results: A facile method for large-scale preparation of 90Y-based mold brachytherapy sources could be established. Conclusions: The source fabrication methodology standardized in this work could be tailored for fabrication of custom-made 90Y sources for individualized treatment of superficial tumors, Bowen's disease, and keloids.

Integrating resilience with functional ecosystem measures: A novel paradigm for management decisions under multiple-stressor interplay in freshwater ecosystems.

Moving beyond monitoring the state of water quality to understanding how the sensitive ecosystems "respond" to complex interplay of climatic and anthropogenic perturbations, and eventually the mechanisms that underpin alterations leading to transitional shifts is crucial for managing freshwater resources. The multiple disturbance dynamics-a single disturbance as opposed to multiple disturbances for recovery and other atrocities-alter aquatic ecosystem in multiple ways, yet the global models lack representation of key processes and feedbacks, impeding potential management decisions. Here, the procedure we have embarked for what is known about the biogeochemical and ecological functions in freshwaters in context of ecosystem resilience, feedbacks, stressors synergies, and compensatory dynamics, is highly relevant for process-based ecosystem models and for developing a novel paradigm toward potential management decisions. This review advocates the need for a more aggressive approach with improved understanding of changes in key ecosystem processes and mechanistic links thereof, regulating resilience and compensatory dynamics concordant with climate and anthropogenic perturbations across a wide range of spatio-temporal scales. This has relevance contexting climate change and anthropogenic pressures for developing proactive and adaptive management strategies for safeguarding freshwater resources and services they provide.

An electrochemical technique for fabrication of Mn-54 sources towards characterization of gamma counting nuclear instruments.

Long lived sealed radioactive sources are used for the energy calibration and efficiency determination of counting systems used in the nuclear sector. Using a sulphate bath, a facile electrochemical method was developed by electrodeposition of 54Mn on 5 mm (φ) stainless steel substrates for the preparation of 54Mn sources for such uses. Inactive sources prepared under suitable experimental parameters characterized by XRD revealed that manganese is deposited in oxide form. SEM and EDS analyses of electrodeposited surfaces confirmed uniform distribution of elements and the absence of fractures, flaws, and spatial variations. Cyclic voltammetry (CV) scans provided information about the electrochemical processes involved in the deposition process. Uniform distribution of radioactivity on surface of source was ascertained by autoradiography. Swipe tests of the encapsulated sources confirmed negligible removable surface contamination. The 54Mn sources containing up to 185KBq of 54Mn on stainless steel discs were prepared. These sources along with other longer lived sources were supplied to various users as a package of radiation sources for characterization of gamma counting systems over a wide energy range.

Monte Carlo-based dosimetric studies of a locally developed170Tm LDR brachytherapy seed source.

170Tm is being explored as a source for applications in brachytherapy. Although it has adequate physical properties, such as a short half-life (128.6 d), high specific activity and a mean photon energy of about 66 keV, it has a drawback of low photon yield (only about six photon emissions/100 beta emissions). The objective of this work is to study the dosimetric characteristics of a locally developed170Tm brachytherapy seed source using the Monte Carlo-based EGSnrc code system. In this study, we calculate the dose rate constant, air-kerma strength, radial dose function, anisotropic function and 2D dose-rate distributions in water. Separate simulations are carried out by considering the photon (gamma and characteristic x-ray) and beta spectra of the source. For regions close to the source (surface of the source

Dose-dependent cell cycle arrest and apoptosis in HER2 breast cancer cells by177Lu-CHX-A"-DTPA-Trastuzumab.

BACKGROUND: Trastuzumab is a Food and Drug Administration-approved humanized monoclonal antibody which targets the extracellular domain of human epidermal growth factor receptor 2 (HER2) receptor overexpressed on HER2-positive breast cancer cells. The combination of Lutetium-177 (177 Lu) (t½= 6.7 days, Eßmax497 keV (78.6%) and trastuzumab makes it a suitable targeting agent for radioimmunotherapy. In preclinical and clinical studies,177 Lu-Trastuzumab has proven to be effective for the treatment of HER2-positive malignancies such as breast and ovarian cancer. OBJECTIVES: In this study, we report the mechanism of action of177 Lu-CHX-A"-diethylenetriaminepentaacetic acid (DTPA)-trastuzumab at the cellular and molecular level by performing various in vitro assays in HER2-positive MDA-MB-453 breast cancer cells. MATERIALS AND METHODS: Trastuzumab was conjugated to the bifunctional chelating agent (BFCA) para-isothiocyanatobenzyl-DTPA and radiolabeled with177 Lu. In vitro cell binding studies were carried out in MDA-MB-453 cells to confirm the specificity of the complex toward the receptor. Cellular toxicity, cell cycle, and cell death analysis were also performed for exploring the potential of the radioimmunoconjugate at cellular and molecular level. RESULTS: In vitro cell binding studies showed a maximum binding of 10.7 ± 0.1% which reduced to 2.9 ± 0.1% on coincubation with unlabeled antibody. Our study revealed that the cellular toxicity was dose dependent, and mode of cell death was predominantly by apoptosis. The radioimmunoconjugate retarded the cell in the S phase of cell cycle with two-fold increase in G2/M arrest which justifies the enhanced apoptosis at higher doses. CONCLUSIONS: The study revealed that the formulation can execute a dose-dependent cellular toxicity through induction of apoptosis.

Preparation and preliminary bioevaluation studies of 68 Ga-NOTA-rituximab fragments as radioimmunoscintigraphic agents for non-Hodgkin lymphoma.

Rituximab is used for the treatment of non-Hodgkin lymphoma (NHL). This study focuses on development of 68 Ga-labeled rituximab fragments, (68 Ga-NOTA-F (ab')-rituximab and 68 Ga-NOTA-F (ab')2 -rituximab, as PET-imaging agents for NHL. Rituximab was digested with immobilized pepsin and papain to yield F (ab')2 and Fab fragments respectively that were characterized by size exclusion HPLC (SE-HPLC) and SDS-PAGE. They were conjugated with p-SCN-Bn-NOTA, labeled with 68 Ga and characterized by SE-HPLC. Intact rituximab was labeled with gallium-68 for comparison. Specificity of 68 Ga-labeled immunoconjugates was ascertained by immunoreactivity and cell binding studies in Raji cells, while biodistribution studies were performed in normal Swiss mice. Gradient SDS-PAGE under nonreducing condition showed molecular weights of F (ab')2 -rituximab and F (ab')-rituximab as approximately 100 and 40 Kd, respectively. Radiochemical purity (RCP) of 68 Ga-NOTA-F (ab')2 -rituximab and 68 Ga-NOTA-F (ab')-rituximab were 98.2 ± 0.5% and 98.8 ± 0.2% respectively with retention times of 17.1 ± 0.1 min and 19.3 ± 0.1 min in SE-HPLC. 68 Ga-labeled rituximab fragments were stable in saline and serum up to 2-hour post preparation and exhibited specificity to CD20 antigen. Immunoreactivity of 68 Ga-labeled immunoconjugates was greater than 80%. Clearance of the fragmented radioimmunoconjugates was predominantly through renal route. Preliminary results from this study demonstrate the potential of 68 Ga- NOTA-F (ab')2 -rituximab and 68 Ga-NOTA-F (ab')-rituximab as PET imaging agents for NHL.

Fabrication of miniature 141Ce sources by chemical deposition towards possible use in the performance evaluation of gamma cameras - A feasibility study.

141Ce sources were fabricated for quality assurance of gamma cameras. The fabrication process consisted of electro-deposition of Ni on a Cu sphere in 0.01 N H2SO4 containing 30 mg/mL H3BO3 and 50 µg of NiSO4·7H2O at pH 2-3 followed by deposition of 141Ce on it. > 95% deposition of 141Ce on substrate could be achieved at pH 5. Source core was loaded in custom-made Al holder. Autoradiography confirmed uniform activity distribution. SEM and EDS analyses confirmed deposition of Cerium on substrate.

Synthesis and Preliminary Biological Evaluation of 177Lu-Labeled Polyhydroxamic Acid Microparticles Toward Therapy of Hepatocellular Carcinoma.

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 177Lu-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 177Lu on PHA microparticles. Stability of 177Lu-PHA microparticles was tested in the presence of competing Fe(III) ions in solution. In vitro stability of 177Lu-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 177Lu-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 177Lu on PHA microparticles could be achieved. Even in the presence of high concentration of Fe(III) ions, 177Lu binding to PHA microparticles was stable. 177Lu-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 177Lu-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 177Lu for treatment of HCC.

Metal Contamination in Seven Tributaries of the Ganga River and Assessment of Human Health Risk from Fish Consumption.

We investigated the distribution of Zn, Cu, Ni, Pb, Cr, and Cd in water, sediment, and two dietary fish (an omnivore, Labeo rohita and a benthic carnivore, Clarias batrachus) and potential health risk to human consumers during summer low flow (2017-2018) at 28 sites across 7 tributary confluences of the Ganga River. We selected Devprayag, an upper reach site, as a reference for data comparison. We found significant spatial variations in the distribution of study metals and the concentrations remained higher in tributaries, confluences, and downstream cities. The pollution load index showed all sites except Devprayag in the polluted category. Ecological risk analysis indicated 1 site with very high risk, 7 with considerable risk, and 10 with moderate-risk category. The Zn did appear the most, and Cd the least accumulated metal in the fish. The metal accumulation was higher in C. batrachus. The levels of Cd, Cr, and Pb in the study fishes were higher compared with the international standards. The health risk analysis indicated safe levels for individual metals except for Cd where the target hazard quotient (THQ) did exceed 1 for C. batrachus at the Ramganga and Varuna confluences. When all metals were considered, the THQ was > 1 (> 2 for C. batrachus), indicating the full possibility of adverse health effects to human consumers. Our study highlights the importance of tributaries in creating a mosaic of metal-rich habitats in the Ganga River and food chain associated with a health risk to human consumers.

Preparation of 177Lu-Trastuzumab injection for treatment of breast cancer.

The objective of this study was the facile preparation of 177Lu-CHX-A''-DTPA-Trastuzumab injection for breast cancer therapy. Trastuzumab conjugated with CHX-A''-DTPA-NCS was radiolabeled with 177Lu in >95% radiochemical purity. In vitro studies in SKBR3 and MDA-MB-453 cells confirmed specificity of 177Lu-CHX-A''-DTPA-Trastuzumab to HER2 positive cells. The radioimmunoconjugate showed good immunoreactivity, in vitro stability in saline and Kd of 1.01 ±â€¯0.13 nM in SKBR3 cells. Clearance of 177Lu-CHX-A''-DTPA-Trastuzumab in Swiss mice was predominantly through the hepatobiliary route with minimal bone uptake.

Preparation of 177 Lu-labeled Nimotuzumab for radioimmunotherapy of EGFR-positive cancers: Comparison of DOTA and CHX-A″-DTPA as bifunctional chelators.

This study was aimed at evaluating the role of bifunctional chelators DOTA-NCS and CHX-A″-DTPA-NCS used for conjugating 177 Lu with Nimotuzumab on the radiochemical yields, purity, in vitro stability, and specificity of the radioimmunoconjugates to EGFR. Two immunoconjugates were prepared wherein Nimotuzumab was conjugated with the acyclic ligand p-NCS-Bn-CHX-A″-DTPA and macrocyclic ligand p-NCS-Bn-DOTA. These were radiolabeled with 177 Lu, purified on PD-10 column, and characterized by SE-HPLC. In vitro stability was determined up to 4 days post preparation. Specificity of the radioimmunoconjugates was ascertained by in vitro studies in A431 cells while the biodistribution patterns were studied in normal Swiss mice up to 96 hours post injection. Four to five molecules of CHX-A″-DTPA/DOTA were attached to one molecule of Nimotuzumab. Radiochemical purity of both 177 Lu-CHX-A″-DTPA-Nimotuzumab and 177 Lu-DOTA-Nimotuzumab was determined to be greater than 98%. Both the radioimmunoconjugates exhibited good in vitro stability at 37°C up to 4 days post preparation in saline, and their clearance was largely by the hepatobiliary route. The DOTA- and CHX-A″-DTPA-based radioimmunoconjugates could be prepared with good radiochemical purity, in vitro stability, and specificity to EGFR. Further studies in EGFR-positive cancers would pave way for them for use in the clinics.

Utilization of Chemical Deposition Technique for Preparation of Miniature 170Tm Sources and Preliminary Quality Assessment for Potential Use in Brachytherapy.

OBJECTIVE: This article describes the preparation of a 170Tm source by chemical deposition technique, its encapsulation in a titanium holder, and preliminary quality evaluation for potential utility as a brachytherapy source. METHODS: The procedure consisted of electrodeposition of Ni on a Cu wire followed by chemical deposition of 170Tm on it. Influence of feed solution pH, carrier Tm concentration, and reaction time were studied for optimum deposition of 170Tm on substrate. After sealing the source core in a titanium capsule, quality control tests were performed. Distribution of 170Tm on substrate was evaluated by autoradiography. Inactive Tm source was characterized by scanning electron microscope (SEM) and energy-dispersive X-ray (EDS) analyses. RESULTS: Under optimized conditions (pH 5, 10 µg Tm carrier, 5 h), 170Tm source core could be prepared by deposition of >95% of 170Tm radioactivity on substrate. Swipe tests and immersion tests on encapsulated sources confirmed that removable radioactivity and radioactivity leakage levels were within stipulated limits. Autoradiography of 170Tm source confirmed uniformity of radioactivity distribution. While SEM analysis confirmed good adhesion of Tm on substrate, EDS analysis confirmed elemental constituents of the Tm-deposited substrate. CONCLUSION: The objective of preparing a 170Tm source by chemical deposition for potential brachytherapy applications could be successfully achieved.

Synthesis and evaluation of 68Ga labeled palmitic acid for cardiac metabolic imaging.

This work evaluates the potential of a 68Ga labeled long chain 16C fatty acid for cardiac metabolic imaging. For radiolabeling with 68Ga, hexadecanedioic acid was coupled with the chelator p-NH2-Bn-NOTA. Under the optimized conditions, NOTA-hexadecanoic acid could be radiolabeled with 68Ga in ≥95% yields. In biodistribution studies carried out in Swiss mice, 68Ga-NOTA-hexadecanoic acid showed low myocardial uptake at 2 min p.i. (3.7 ±â€¯1.3%ID/g). While 68Ga-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 68Ga-NOTA-hexadecanoic acid confirmed its metabolic transformation in the myocardium.

Clinical experience with indigenous kit-based preparation of 68Ga-DOTATOC using commercial 68Ge/68Ga generator.

Pharmaceutical grade DOTATOC kits compliant with all the quality control criteria were formulated and radiolabeled with 68Ga in high yields. Comparison with module-based 68Ga-DOTATOC established product equivalency. Clinical utility was evaluated in patients with histopathologically confirmed well-differentiated neuroendocrine tumors. Kit-based preparation of 68Ga-DOTATOC could identify sites of primary and metastatic disease. PET/CT images of patients conformed to the established criteria for somatostatin imaging agents and clinical expectations. Results of this study emphasize the potential of kit-based 68Ga-DOTATOC for PET imaging of neuroendocrine tumors.

Preparation of Radioactive Skin Patches Using Polyhydroxamic Acid-Grafted Cellulose Films Toward Applications in Treatment of Superficial Tumors.

The primary objective of this investigation is the development of a strategy for the synthesis of polyhydroxamic acid (PHA)-grafted cellulose film, its characterization, and evaluation of its usefulness for the preparation of 177Lu skin patches for superficial brachytherapy applications. PHA-grafted cellulose films were synthesized and characterized by Fourier transformed infrared spectrometer analysis and visual color test with Fe(III) solution. Uptake of 177Lu on the PHA-grafted cellulose was investigated by varying the experimental conditions such as the pH of feed solution, amount of nonradioactive Lu carrier, time, and temperature of the reaction. Under the optimized conditions, >95% loading of 177Lu on the PHA-cellulose film could be achieved. Autoradiography studies of 177Lu-PHA-cellulose film confirmed the uniform distribution of 177Lu on the surface. Energy dispersive X-ray analysis of nonradioactive Lu-PHA-cellulose film confirmed the loading of Lu on PHA-cellulose film. The utility of PHA-functionalized cellulose films for the fabrication of radioactive sources for superficial brachytherapy applications could be successfully demonstrated.

68Ga labeled Erlotinib: A novel PET probe for imaging EGFR over-expressing tumors.

Molecular imaging using radiolabeled Tyrosine Kinase Inhibitors (TKI) is a promising strategy for detection and staging of EGFR-positive cancers. A novel analogue of one such TKI, Erlotinib has been developed for PET imaging by derivatizing the parent Erlotinib molecule for conjugation with the bifunctional chelator p-SCN-Bn-NOTA towards radiolabeling with 68Ga. NOTA-Erlotinib conjugate was synthesized and characterized by NMR and ESI-MS techniques. The conjugate was radiolabeled with 68Ga in 95±2% yield, as evidenced by HPLC characterization. The logP value of 68Ga-NOTA-Erlotinib was - (0.6±0.1). The 68Ga-NOTA-Erlotinib conjugate was characterized using its natGa-NOTA-Erlotinib surrogate. Cell viability studies showed that the NOTA-Erlotinib conjugate retained the biological efficacy of the parent Erlotinib molecule. Further, 68Ga-NOTA-Erlotinib exhibited an uptake of 9.8±0.4% in A431 cells which was inhibited by 55.1±0.2% on addition of cold Erlotinib (10µg) confirming the specificity of the radioconjugate for EGFR expressing cells. In the biodistribution studies carried out in tumor bearing SCID mice, 68Ga-NOTA-Erlotinib conjugate showed moderate tumor accumulation (1.5±0.1% ID/g at 30minp.i.; 0.7±0.2% ID/g at 1hp.i.). Hepatobiliary clearance of the radioconjugate was observed. The 68Ga-NOTA-Erlotinib conjugate was found to have high in vivo stability as determined by the metabolite analysis study using urine sample of the Swiss mice injected with the preparation. The overall properties of 68Ga-NOTA-Erlotinib are promising and merit further exploration. To the best of our knowledge, this is the first report on the design of a 68Ga labeled Erlotinib for PET imaging of EGFR and opens avenues for the successful development of 68Ga labeled TKI for imaging of EGFR over-expressing tumors.

A systematic study on the utility of CHX-A''-DTPA-NCS and NOTA-NCS as bifunctional chelators for 177Lu radiopharmaceuticals.

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 177Lu. While 177Lu-CHX-A''-DTPA-NCS could be obtained in high yields at equimolar ratios of lutetium to CHX-A''-DTPA-NCS, >95% yield of 177Lu-NOTA-NCS could be achieved at 1:2M ratio of lutetium to NOTA-NCS. Trace metals reduced the yields of 177Lu-NOTA-NCS significantly as compared to 177Lu-CHX-A''-DTPA-NCS. In vitro stability of 177Lu-CHX-A''-DTPA-NCS was also superior to 177Lu-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 177Lu radiopharmaceuticals.

Initial Clinical Experience with 68Ga-DOTA-NOC Prepared Using 68Ga from Nanoceria-polyacrylonitrile Composite Sorbent-based 68Ge/68Ga Generator and Freeze-dried DOTA-NOC Kits.

Somatostatin receptor positron emission tomography-computed tomography (PET/CT) with 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) peptides have become an indispensable part of disease assessment in patients with neuroendocrine tumors and forms the basis of personalized therapy with peptide receptor-based radionuclide therapy. With growing utilization of PET/CT in developing countries, availability of the indigenous GMP-certified 68Ge/68Ga generators is expected to further promote cost-effective molecular imaging service to the cancer patients. We present our initial clinical experience in 32 patients injected with 68Ga-DOTA-NOC prepared using 68Ga eluted from Bhabha Atomic Research Centre nanoceria-polyacrylonitrile sorbent-based 68Ge/68Ga generator and freeze-dried DOTA-NOC cold kits.