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New modes of production and supply of short-lived radioisotopes using accelerators are becoming attractive alternatives to the use of nuclear reactors. In this study, the use of a compact accelerator neutron source (CANS) was implemented to explore the production of 99mTc and 101Tc. Irradiations were performed with neutrons generated from a 16.5 MeV cyclotron utilising the 18O(p, n)18F reaction during routine 18F[FDG] production in a commercial radiopharmacy. Natural molybdenum targets in metal form were employed for the production of Tc isotopes of interest via (n, ) reactions on 98Mo and 100Mo. The production of 99mTc and 101Tc under these conditions is considered and discussed.

The upregulation of epithelial cell adhesion molecule (EpCAM) expression, found in a substantial fraction of renal cell carcinomas (RCCs), renders it a potential molecular target for the treatment of disseminated RCC. However, the heterogeneous expression of EpCAM necessitates first identifying the patients with sufficiently high expression of EpCAM in tumors. Using the specific radionuclide-based visualization of EpCAM might enable such identification. The designed ankyrin repeat protein, Ec1, is a small (molecular weight, 18 kDa) targeting protein with a subnanomolar affinity to EpCAM. Using a modified Ec1, a tracer was developed for the radionuclide-based visualization of EpCAM in vivo, i.e., an EpCAM-visualizing designed ankyrin repeat protein (EVD). EVD was labelled with either technetium-99m using technetium tricarbonyl or with iodine-125 (as a surrogate for iodine-123) by coupling it to para-[I-125]iodobenzoyl ([I-125]PIB) groups. Both the I-125-labelled EVD (I-125-EVD) and Tc-99m-labelled EVD (Tc-99m-EVD) bound specifically to EpCAM-expressing SK-RC-52 renal carcinoma cells. The binding affinity (K-D value) of Tc-99m-EVD to SK-RC-52 cells was 400 +/- 28 pM. The tracers' uptake in SK-RC-52 xenografts at 3 h after injection was 5.2 +/- 1.4%ID/g for I-125-EVD and 6.0 +/- 1.4%ID/g for Tc-99m-EVD (no significant difference). These uptake values in SK-RC-52 xenografts were significantly higher (P

Ideal nuclear imaging tracers should exhibit high target uptake and low background signal. Traditional renal scintigraphy and SPECT scans examine kidney function via static or dynamic tracing of radioactive probes in the kidneys. The lack of tracer affinity to specific biological processes and high background uptake from urinary excretion have added many difficulties to precision renal diagnosis. In this issue of Theranostics, Jin and colleagues innovatively devised a recombinant probe for preferential kidney imaging through targeting of tubular neonatal Fc receptor and proximal tubular basement membrane for sustained tubular reabsorption and accumulation. This work has broad implications regarding how an in depth understanding of physiology and pathology may be of service for tracer development, renal diagnosis, and disease theranostics.

This study aims to investigate radiolabeled Cefpodoxime Proxetil loaded chitosan (CP–CS) nanoparticles as nuclear imaging infection agent to Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). The encapsulation efficiency of Cefpodoxime Proxetil was found 82 ± 2%. CP and CP–CS nanoparticles were radiolabeled with Tc-99 m. The radiochemical purity of 99mTc–CP and 99mTc–CP–CS nanoparticles were determined by RTLC as 89 ± 3% and 94 ± 2% respectively. In vitro bindings of 99mTc–CP–CS nanoparticles to S. aureus and E. coli were found higher than 99mTc–CP bindings. © 2020, Akadémiai Kiadó, Budapest, Hungary.

Monte Carlo simulation method and Nuclear Medicine MIRD method were used to evaluate the effect of ra-diopharmaceuticals on Covid-19 disease. The mean absorbed organ dose in the target organ and gamma radi-ation emitter attenuation properties such as linear attenuation coefficients, energy absorption build-up factors (EABF), exposure build-up factors (EBF), and relative dose distributions (RDD) were examined. The results showed that radiopharmaceuticals containing gamma radiation emitters which are densely ionizing charged particles induced membrane damage and produced protein damage.

Recently, radiolabelled antagonists targeting somatostatin receptors subtype 2 (SST2) in neuroendocrine neoplasms demonstrated certain superior properties over agonists. Within the ERA-PerMED project &ldquo, TECANT&rdquo, two 99mTc-Tetramine (N4)-derivatized SST2 antagonists (TECANT-1 and TECANT-2) were studied for the selection of the best candidate for clinical translation. Receptor-affinity, internalization and dissociation studies were performed in human embryonic kidney-293 (HEK293) cells transfected with the human SST2 (HEK-SST2). Log D, protein binding and stability in human serum were assessed. Biodistribution and SPECT/CT studies were carried out in nude mice bearing HEK-SST2 xenografts, together with dosimetric estimations from mouse-to-man. [99mTc]Tc-TECANT-1 showed higher hydrophilicity and lower protein binding than [99mTc]-TECANT-2, while stability was comparable. Both radiotracers revealed similar binding affinity, while [99mTc]Tc-TECANT-1 had higher cellular uptake (&gt, 50%, at 2 h/37 &deg, C) and lower dissociation rate (&lt, 30%, at 2 h/37 &deg, C). In vivo, [99mTc]Tc-TECANT-1 showed lower blood values, kidney and muscles uptake, whereas tumour uptake was comparable to [99mTc]Tc-TECANT-2. SPECT/CT imaging confirmed the biodistribution results, providing the best tumour-to-background image contrast for [99mTc]Tc-TECANT-1 at 4 h post-injection (p.i.). The estimated radiation dose amounted to approximately 6 &micro, Sv/MBq for both radiotracers. This preclinical study provided the basis of selection of [99mTc]Tc-TECANT-1 for clinical translation of the first 99mTc-based SST2 antagonist.

Non-invasive radionuclide imaging of human epidermal growth factor receptor type 2 (HER2) expression in breast, gastroesophageal, and ovarian cancers may stratify patients for treatment using HER2-targeted therapeutics. Designed ankyrin repeat proteins (DARPins) are a promising type of targeting probe for radionuclide imaging. In clinical studies, the DARPin [Tc-99m]Tc-(HE)(3)-G3 labeled using a peptide-based chelator His-Glu-His-Glu-His-Glu ((HE)(3)), provided clear imaging of HER2 expressing breast cancer 2-4 h after injection. The goal of this study was to evaluate if the use of cysteine-containing peptide-based chelators Glu-Glu-Glu-Cys (E3C), Gly-Gly-Gly-Cys (G(3)C), and Gly-Gly-Gly-Ser-Cys connected via a (Gly-Gly-Gly-Ser)(3)-linker (designated as G3-(G(3)S)(3)C) would further improve the contrast of imaging using Tc-99m-labeled derivatives of G3. The labeling of the new variants of G3 provided a radiochemical yield of over 95%. Labeled G3 variants bound specifically to human HER2-expressing cancer cell lines with affinities in the range of 1.9-5 nM. Biodistribution of [Tc-99m]Tc-G3-G(3)C, [Tc-99m]Tc-G3-(G(3)S)(3)C, and [Tc-99m]Tc-G3-E3C in mice was compared with the biodistribution of [Tc-99m]Tc-(HE)(3)-G3. It was found that the novel variants provide specific accumulation in HER2-expressing human xenografts and enable discrimination between tumors with high and low HER2 expression. However, [Tc-99m]Tc-(HE)(3)-G3 provided better contrast between tumors and the most frequent metastatic sites of HER2-expressing cancers and is therefore more suitable for clinical applications.

4th International Conference on Computational and Experimental Science and Engineering (ICCESEN) -- OCT 04-08, 2017 -- Kemer, TURKEY WOS: 000478894500038 To date, myocardial perfusion (MP) has been utilized to assess the adequacy of blood flow to the myocardium in order to determine the ischemic heart diseases. With the advent of SPECT/CT, MP became the most common investigation in the field of nuclear cardiology with more accuracy and details. Thallium-201 and Technetium-99m (Tc-99m) have been early used in cardiac nuclear imaging. Half-life of Tc-99m is 6 h, and its energy is 140 keV, while the half-life of Tl-201 is as longer as 73 h, its X-ray energies range between 69 and 81 kV in addition to gamma rays of 135 keV and 167 keV. The purpose of the present study was to explore the radiation dose rates emitted from the patients following Tc-99m sestamibi injection. To achieve that, the radiation emanated to the environment was measured at different distances from patients and various time intervals for 20 patients using GM counter. The mean radioactivity administered to the patients was 391.1 MBq (10.6 mCi), with a range between 276.8 MBq to maximum of 515.4 MBq. Radiation dose rate was found 9.07 mu Sv h(-1) at 1 m distance from the patient's chest level after 7.6 min, then decayed to 7.93 mu Sv h(-1) after 36.5 min, and 7.83 mu Sv h(-1) later to 66.4 min. It was concluded that 1 m distance from the patients sounds sensibly adequate to maintain the occupational dose within the safe limit following Tc-99m sestamibi injection, while verification of public dose rate

Background: Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used for targeted drug delivery systems due to their unique magnetic properties. Objective: In this study, it has been aimed to develop a novel targeted Tc-99m radiolabeled polymeric drug delivery system for Gemcitabine (GEM). Methods: Gemcitabine, an anticancer agent, was encapsulated into polymer nanoparticles (PLGA) together with iron oxide nanoparticles via double emulsion technique and then labeled with Tc-99m. SPIONs were synthesized by reduction-coprecipitation method and encapsulated with oleic acid for surface modification. Size distribution and the morphology of the synthesized nanoparticles were characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. The radiolabeling yield of SPION-PLGAGEM nanoparticles was determined via Thin Layer Radio Chromatography (TLRC). Cytotoxicity of GEM loaded SPION-PLGA was investigated on MDA-MB-231 and MCF7 breast cancer cells in vitro. Results: SEM images displayed that the average size of the drug-free nanoparticles was 40 nm and the size of the drug-loaded nanoparticles was 50 nm. The diameter of nanoparticles was deter- mined as 366.6 nm by DLS, while zeta potential was found as 29 mV. SPION was successfully coated with PLGA, which was confirmed by FTIR. GEM encapsulation efficiency of SPION-PLGA was calculated as 4 +/- 0.16% by means of HPLC. Radiolabeling yield of SPION-PLGA-GEM nanoparticles was determined as 97.8 +/- 1.75% via TLRC. Cytotoxicity of GEM loaded SPION-PLGA was investigated on MDA-MB-231 and MCF7 breast cancer cells. SPION-PLGA-GEM showed high uptake on MCF-7, while the incorporation rate was increased for both cell lines with external magnetic field application. Conclusion: Tc-99m labeled SPION-PLGA nanoparticles loaded with GEM may overcome some of the obstacles in anti-cancer drug delivery because of their appropriate size, non-toxic, and super-paramagnetic characteristics, Celal Bayar University Scientific Research Projects Coordination Unit [2017-001], Celal Bayar University Scientific Research Projects Coordination Unit (Grant Number: 2017-001).

The aim of this study is the synthesis of a novel Tc-99m-labeld graft polymer and the biological evaluation of its in vitro and in vivo properties. To this end, a L-proline-graft-poly(HEMA) was prepared and labeled with Tc-99m. The radiochemical yield of approximately the Tc-99m-labeled compound amounted to 97 +/- 2.3%. The cytotoxicity test revealed no cytotoxic effect after a 24- and 48-h incubation. The results of the hemolysis test showed that hemolysis was non-toxic with an effect level of less than 2%. Subsequently, the biodistribution in healthy rats was determined. High accumulation of the polymer was observed in the pancreas, thyroid and prostate., Manisa Celal Bayar University Coordination Unit of Scientific Research Projects (BAP) [2017-016], The authors are thankful for the financial support from the Manisa Celal Bayar University Coordination Unit of Scientific Research Projects (BAP) (Project number: 2017-016). We thank to Buket Ate for the technical assistance during the animal experiments. We also thank Norma R. de Yagcier and Mahdi Rajabimovahed for reviewing our study as native English speakers.

The purpose of this study was to develop a multifunctional theranostic probe for imaging (magnetic resonance imaging [MRI] and single-photon emission computed tomography [SPECT]) and therapy (photodynamic therapy). For this purpose, Tc-99m-labeled lupulone-conjugated Fe3O4@TiO2 nanocomposites (Tc-99m-DTPA-Fe3O4@TiO2-HLP and Tc-99m-DTPA-Fe3O4@TiO2-ALP nanocomposites) were synthesized. The average diameter of the nanocomposites was 171 +/- 20 nm as seen on transmission electron microscopy images. Fe3O4@TiO2 nanocomposites exhibited fluorescence spectra at an emission wavelength of 314 nm. Lupulone-conjugated Fe3O4@TiO2 nanocomposites were spherical-shaped with a suitable dispersion and without visible aggregation, and their radiolabeling yields were over 85%. Healthy (RWPE-1 normal human prostate epithelial cell line) and cancer prostate cell lines (PC-3 human prostate cancer cell line) were used to determine the in vitro biological behavior of the nanocomposites. The PC-3 cells treated with lupulone-conjugated Fe3O4@TiO2 nanocomposites showed a lower cell viability compared with RWPE-1 cells treated with lupulone-conjugated Fe3O4@TiO2 nanocomposites. Lupulone-modified Fe3O4@TiO2 nanocomposites may serve in the future as a multifunctional probe for positron emission tomography (PET)/MRI, photodynamic therapy, and hyperthermia therapy of cancer., National Cancer Institute [P30 CA008748], National Cancer Institute, Grant/Award Number: P30 CA008748

Background: The [99mTc][Tc(N)(PNP)] system, where PNP is a bisphosphinoamine, is an interesting platform for the development of tumor ‘receptor-specific’ agents. Here, we compared the reactivity and impact of three [Tc(N)(PNP)] frameworks on the stability, receptor targeting properties, biodistribution, and metabolism of the corresponding [99mTc][Tc(N)(PNP)]-tagged cRGDfK peptide to determine the best performing agent and to select the framework useful for the preparation of [99mTc][Tc(N)(PNP)]-housing molecular targeting agents. Methods: cRGDfK pentapeptide was conjugated to Cys and labeled with each [Tc(N)(PNP)] framework. Radioconjugates were assessed for their lipophilicity, stability, in vitro and in vivo targeting properties, and performance. Results: All compounds were equally synthetically accessible and easy to purify (RCY ≥ 95%). The main influences of the synthon on the targeting peptide were observed in in vitro cell binding and in vivo. Conclusions: The variation in the substituents on the phosphorus atoms of the PNP enables a fine tuning of the biological features of the radioconjugates. ws[99mTc][Tc(N)(PNP3OH)]– and [99mTc][Tc(N)(PNP3)]– are better performing synthons in terms of labeling efficiency and in vivo performance than the [99mTc][Tc(N)(PNP43)] framework and are therefore more suitable for further radiopharmaceutical purposes. Furthermore, the good labeling properties of the ws[99mTc][Tc(N)(PNP3OH)]– framework can be exploited to extend this technology to the labeling of temperature-sensitive biomolecules suitable for SPECT imaging.

We present a 74-year-old woman with primary hyperparathyroidism, with elevated parathyroid hormone and calcium. Tc-99m-methoxyisobutyl isonitrile (sestamibi) planar imaging showed a focus of uptake over the inferior aspect of the right submandibular gland that was localized on the single-photon emission computed tomography with CT.

Affibody molecules are the most studied class of engineered scaffold proteins (ESPs) in radionuclide molecular imaging. Attempts to use affibody molecules directly labelled with radiometals for targeted radionuclide therapy were hampered by the high uptake and retention of radioactivity in kidneys. Several promising strategies have been implemented to circumvent this problem. Here, we investigated whether a pharmacological approach targeting different components of the reabsorption system could be used to lower the uptake of [99mTc]Tc-ZHER:2395 affibody molecule in kidneys. Pre-injection of probenecid, furosemide, mannitol or colchicine had no influence on activity uptake in kidneys compared to the control group. Mice pre-injected with maleate and fructose had 33% and 51% reduction in the kidney-associated activity, respectively, compared to the control group. Autoradiography images showed that the accumulation of activity after [99mTc]Tc-ZHER2:2395 injection was in the renal cortex and that both maleate and fructose could significantly reduce it. Results from this study demonstrate that pharmacological intervention with maleate and fructose was effective in reducing the kidney uptake of affibody molecules. A presumable mechanism is the disruption of ATP-mediated cellular uptake and endocytosis processes of affibody molecules by tubular cells.

Kanser sözcüğü latince yengeç anlamına gelmekte ve tümörün bedenin herhangi bir bölgesine yengeç gibi ayrılmaz bir şekilde yapıştığını tanımlamak üzere kullanılmaktadır. Günümüzde kalp ve damar hastalıklarından meydana gelen ölümleri, kanser nedeniyle meydana gelen ölümler izlemektedir. Bu nedenle kanserin kontrolü ve önlenmesi çok önemlidir. Tümörler genelde hücrelerin anormal şekilde büyümeleri ile teşhis edilirler. Tümör; normal dokuları aşan, normal dokularla koordine olmayan ve değişime uğradıktan sonra bile aynı şekilde aşırı büyümeye devam eden anormal doku kütlesidir. Bu dokuların anormal büyümesine yol açan en önemli faktörlerden biri olan Vasküler Endotel Büyüme Faktörü (VEGF), hipoksik koşullarda hücrelerden salınarak anjiogenezisi uyarır. Hipoksi ve kanser, üzerinde geniş araştırmalar yapılan önemli bir çalışma alanıdır. Genel inanış, “lokal ileri kanser” tiplerinde hipoksinin temel patofizyolojik etmen olduğu şeklindedir. Öyle ki, lokal ileri aşamadaki pek çok tümör tipinde, tümör dokusunda % 60'a varan oranda hipoksi bulunmaktadır. Hipoksiye maruz kalan tümör hücreleri daha saldırgan fenotipe dönüşmektedir. Hipoksinin, tümör kitlesinin belirli hücre gruplarında tümör progresyonuna yol açtığı son zamanlarda belirlenmiş bir konudur. Birçok tümör tipi için hipoksinin sağkalımı etkilediği anlaşılmaktadır. Hipoksiyle ilgili günümüzde birçok Pozitron Emisyon Tomografisi (PET) ve Tek Foton Emisyonlu Bilgisayarlı Tomografi (SPECT) görüntüleme çalışmaları literatürde mevcuttur. Planlanan bu çalışma ile yeni hipoksi probların sentezi ve bunların Tc-99m ve I-131 ile radyo işaretli bileşikleri oluşturularak, hipoksik alanların ve Vasküler Endotelyal Büyüme Faktörü (VEGF)'nin aynı anda görüntülenmesi hedeflenmiştir. Sentezlenen radyo işaretli hipoksi probların görüntüleme potansiyelleri; başta Meme Adenokarsinoma (MCF-7), Kolon Adenokarsinoma Epiteli (Caco-2) ve Sünnet Derisi Epiteli (BJ) tümör hücreleri olmak üzere farklı hücre hatları üzerinde hücre kültürü çalışmaları ile gerçekleştirilmiştir. Çalışmanın in vivo deneysel aşamasında ise; Caco2 hücreleri ekilmiş döllenmiş yumurta Korioallantoik Membran Model (CAM) membranına, sentezlenen hipoksik ajanlar enjekte edilerek, mikroskobik görüntüler alınmıştır., Cancer word means crab in Latin language and uses to describe the sticking of tumor to any where of body like a crab. Today deaths by heart and vascular diseases followed by deaths caused cancer. Therefore control and prevention of cancer is very important. Tumors are generally identified by growth of cells abnormally. Tumor beyond the normal tissues, in the same way even after being coordinated with nonnormal tissue overgrowth, which is an abnormal mass of tissue that continue to change. Vascular Endothelial Growth Factor (VEGF), which is one of the most important factors that lead to abnormal growth of this tissues, stimulates angiogenesis swing of cells in hypoxic conditions. Hypoxia and cancer are an important area of work done extensive research on. Widely belief, "locally advanced cancer" has been accepted as the basic pathophysiological factors in the types of hypoxia. In fact, in many tumor types in locally advanced stage tumor tissue hypoxia convenience of up to 60 %. Tumor cells which are exposed to hypoxia have more aggressive phenotype. It is recently identified issue that hypoxia causes tumor progression in certain cell groups of tumour. For many tumor types, it is understood that hypoxia affects survival. Many contemporary Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging studies related to hypoxia are available in the literature. Synthesizing the novel hypoxia probe, their Tc-99m and I-131 radiolabeled compounds and imaging both hypoxic areas and Vascular Endothelial Growth Factor (VEGF) at the same time were planned in this study. Imaging potentials of synthesized radiolabeled hypoxia probes will be determinated by cell culture studies on Breast Carcinoma Cells (MCF-7), Colon Adenocarcinoma Epithelium (Caco-2) and Foreskin Epithelium (BJ) cell lines. In the in vivo experimental phase of the study; microscopic images were taken by injecting the synthesized hypoxic agents to the fertilized egg Chorioallantoic Membrane Model (CAM) membrane with inoculated Caco-2 cells.

Technetium-99m (Tc-99m) labeled tetrofosmin kit has been widely used in hospitals including in Indonesia. Usually, tetrofosmin kits and Tc-99m pertechnetate are supplied separately, but recently there has been a new trend where Tc-99m tetrofosmin is supplied in the form of the ready-to-inject product. To prepare such a product it has to be proven that tetrofosmin can be labeled with high activity of Tc-99m and the resulted Tc-99m tetrofosmin, remains stable within shipping time until being used in hospitals. In this investigation, locally produced tetrofosmin kits were labeled with various radioactivity of Tc-99m ranging from 150 mCi to 400 mCi, their radiolabeling yields or radiochemical purity was analyzed using SepPak C18 column, and the radiochemical stability was assessed within 30 hours. The worst storage condition was also studied by analyzing its radiochemical purity after being stored at extreme temperatures for several hours. The results showed that tetrofosmin kit can be highly labeled with up to 415 mCi of Tc-99m, and stable up to 30 hours in room temperature, and there is a tendency that higher radioactivity leads to more decreasing in radiochemical purity. Stability study in extreme temperatures showed that the product can withstand its stability within 6 hours in 40°C, but it decreased rapidly to less than 70% within 1 hour when stored in 50°C. It concludes that the quality of Tc-99m tetrofosmin as an injectable radiopharmaceutical can be maintained during transportation by storing it at cool temperature.

Background: Emerging data from published studies are demonstrating the superiority of Ga-68 PSMA PET/CT imaging in prostate cancer. However, the low yield of the Ge68/Ga-68 from which Gallium-68 is obtained and fewer installed PET/CT systems compared to the SPECT imaging systems may limit its availability. We, therefore, evaluated in a head-to-head comparison, the diagnostic sensitivity of Ga-68 PSMA PET/CT and Tc-99m PSMA SPECT/CT in patients with prostate cancer.Methods: A total of 14 patients with histologically confirmed prostate cancer were prospectively recruited to undergo Ga-68 PSMA PET/CT and Tc-99m HYNIC PSMA SPECT/CT. The mean age of patients was 67.21 +/- 8.15 years and the median PSA level was 45.18 ng/mL (range = 1.51-687 ng/mL). SUVmax of all lesions and the size of lymph nodes with PSMA avidity on Ga-68 PSMA PET/CT were determined. Proportions of these lesions detected on Tc-99m HYNIC PSMA SPECT/CT read independent of PET/CT findings were determined.Results: A total of 46 lesions were seen on Ga-68 PSMA PET/CT localized to the prostate (n = 10), lymphnodes (n = 24), and bones (n = 12). Of these, Tc-99m HYNIC PSMA SPECT/CT detected 36 lesions: Prostate = 10/10 (100%), lymph nodes = 15/24 (62.5%), and bones = 11/12 (91.7%) with an overall sensitivity of 78.3%. Lesions detected on Tc-99m HYNIC PSMA SPECT/CT were bigger in size (P Conclusion: Tc-99m HYNIC PSMA may be a useful in imaging of prostate cancer although with a lower sensitivity for lesion detection compared to Ga-68 PSMA PET/CT. Its use is recommended when Ga-68 PSMA is not readily available, in planning radio-guided surgery or the patient is being considered for radio-ligand therapy with Lu-177 PSMA. It performs poorly in detecting small-sized lesions hence its use is not recommended in patients with small volume disease.

Radiolabeled amino acids as metabolic tracers are increasingly important for imaging and therapy applications. There are only a few reports on Tc-99m-labeled amino acids that have been evaluated in vivo. In this work we coupled a small and highly potent chelator for the fac-[Tc-99m(CO)(3)](+) core to Ltyrosine through a poly(ethylene glycol) linker and investigated the in vivo biodistribution of the Tc-99m-labeled L-tyrosine derivative. In vivo evaluation and biodistribution in mice bearing C6tumor xenografts revealed little tumor and pancreas uptake. The microSPECT images showed rapid clearance from the blood pool. Fast uptake into the gallbladder and an extended residence time makes this labeled tyrosine suitable for gallbladder imaging and associated dysfunctions.

Radiolabeled amino acids as metabolic tracers are increasingly important for imaging and therapy applications. There are only a few reports on Tc-99m-labeled amino acids that have been evaluated in vivo. In this work we coupled a small and highly potent chelator for the fac-[Tc-99m(CO)(3)](+) core to Ltyrosine through a poly(ethylene glycol) linker and investigated the in vivo biodistribution of the Tc-99m-labeled L-tyrosine derivative. In vivo evaluation and biodistribution in mice bearing C6tumor xenografts revealed little tumor and pancreas uptake. The microSPECT images showed rapid clearance from the blood pool. Fast uptake into the gallbladder and an extended residence time makes this labeled tyrosine suitable for gallbladder imaging and associated dysfunctions.

The shortage of nuclear-reactor-based Tc-99m supply has led to increased research on cyclotron-based Tc-99m production. In this paper, Tc-99m radionuclides produced by a 11-MeV proton cyclotron is theoretically discussed in terms of the optimum thickness of nat Mo, nat MoO 3 , and enriched 100 Mo targets; expected impurities; and radioactivity yields of several (p,2n), (p,n), and (p,γ) based nuclear reactions. The SRIM 2013 codes and TALYS 2014 codes are employed to calculate the range of 11-MeV proton beams in the Mo-based targets and the excitation functions of the selected nuclear reactions, respectively. The calculated results indicate that 94m,95m,96m Tc radionuclides would give rise to radionuclide impurities at the end of irradiation for nat Mo targets, whereas no significant impurities were theoretically detected for the enriched 100 Mo target. At the end of bombardment, nearly 42.18 GBq/µA.hr of Tc-99m radionuclide is predicted to result in the 11-MeV proton-irradiated 100 Mo target.

Technetium-99m labeled radiopharmaceutical is commonly used in nuclear medicines as a diagnostic agent, by mixing the sterile kit with Tc-99m. Manufacturing of kits requires an aseptic facility which need to be well designed and maintained according to cGMP, since mostly kits can not be terminally sterilized. Radiopharmaceuticals as pharmaceuticals containing radionuclide is assumed to have an autosterilization property, but correlation between radioactivity and capability of killing microorganisms has to be studied so far. The aim of this study is to investigate the effect of radioactivity on the autosterilization process of radiopharmaceuticals. The study was carried out by adding Tc-99m of various radioactivity into non-sterile tetrofosmin kits, then the samples were tested for sterility. Sterile tetrofosmin kit and non-sterile kit with no Tc-99m added will be used as a negative control and positive control respectively. The sterility was tested using standard direct inoculation method, by inoculating samples in culture media for both bacteria and fungi and observing qualitatively within 14 days. The results showed that the samples with radioactivity of 1, 3 and 5 mCi changed the clarity of the media to turbid, conformed with the performance of positive controls but samples with radioactivity of 10 mCi and 20 mCi did not change the clarity of the media, conformed with the performance of negative control, indicating neither growth of bacteria nor fungi. It is concluded that Tc-99m behaves as an autosterilizing agent at certain radioactivity. Therefore the preparation of Tc-99m radiopharmaceutical can be considered as terminal sterilization rather than aseptic preparation.

UNAK, PERIHAN/0000-0002-5464-2987; Gulcemal, Suleyman/0000-0003-2738-3219, WOS: 000498291900045, PubMed: 31470192, Fe3O4 magnetic graft-Lys-poly(HEMA) was synthesized, labeled with Tc-99m for the first time and its radiopharmaceutical potential was investigated using animal models in this study. Quality control procedures were carried out using thin layer radiochromatography. the labeling yield of radiolabeled polymer was found to be about 100%. Then, stability and lipophilicity were determined. the lipophilicity of Tc-99m labeled Fe3O4 graft-Lys-poly(HEMA) was found to be 3.77. the serum stability experiments demonstrated that approximately 100% of radiolabeled polymer existed as an intact complex in the rat serum within 240 min. Biodistribution of radiolabeled magnetic graft-Lys-poly(HEMA) was performed on female Albino Wistar rats by scintigraphy and biodistribution studies. High uptake was seen in the stomach, the pancreas, brain, ovarian, intestines and the breast., Manisa Celal Bayar University Coordination Unit of Scientific Research Projects (BAP) [2017-016], The authors are thankful for the financial support from the Manisa Celal Bayar University Coordination Unit of Scientific Research Projects (BAP) (Project number: 2017-016).

Ziel: Die SIRT-Therapieplanung erfolgt anhand der hepatischen Tc-99m-MAA-SPECT/CT. Ergänzend kann mittels C-Arm CT die Identifikation der Segmentversorgung und der Zielläsionen verbessert werden. Ziel dieser Arbeit war die Darstellbarkeit der Zielläsionen sowie die Korrelation des tumoralen Tc-99m-MAA-Uptakes mit dem C-Arm CT-Parameter parenchymales Blutvolumen (PBV) bei HCC und Leberherden von Kolonkarzinomen (CRC). Methodik: 34 Patienten erhielten ein PBV-C-Arm CT (Artis Zeego Q;Siemens Healthineers), gefolgt von einer Tc-99m MAA-Injektion (96±26 MBq). Die quantitative SPECT/CT erfolgte ca. 1h p.i. (Discovery 670pro; GE Healthcare). MAA-Uptake und PBV-Karten wurden visuell per Likert-Scale sowie semiquantitativ (MAA-Tumor/Leber-Uptake (=TBR) bzw. PBV in ml/100ml) ausgewertet und miteinander korreliert. Ergebnisse: Die visuelle Analyse der Darstellbarkeit der 102 untersuchten Läsionen (54 CRC, 48 HCC) zeigte eine sehr gute Übereinstimmung zwischen PBV und TBR für beide Tumorentitäten (Übereinstimmung HCC bzw. CRC: genau 52%/50%; partiell: 38%/39%; keine 10%/11%). Die HCCs zeigten ggü. den CRC einen signifikant höheren MAA-Uptake (108 vs. 55, p

Bu tez çalışmasının amacı, daha çevreci, ekonomik yeşil sentez denebilecek doğal bileşikler ve nanomateryaller sentezlenerek yeni sıvı sintilasyon materyalleri oluşturmaktır. Oluşturulan yapılardan birisi Lawson molekülünün (2-hydroxy-1,4- naphthoquinone) fosfat içeren türevi olan Lawson diphosphate (Lawson-P)’dır. Bunun için çıkış maddesi olarak kına (Lawsonia inermis) bitkisinin bileşenlerinden biri olan Lawson molekülü fosforillenerek Lawsondiphosphate (Lawson–P) sentezlenmiştir. Daha sonraki aşamada ise silikalanarak silikalı Lawson-P (LW-PO-( Si(OH)3) oluşturulmuştur. Üzerinde çalışılan diğer sistem ise TiO2 nanoparçacıkları ve silikalı ve silanlı türevleridir. Bunun için TiO2 nanoparçacıkları sentezlenmiş, silika ile kaplanarak silikalı TiO2 nanoparçacıkları (TiO2-O-Si(OH)3) ve silanlı TiO2 nanoparçacıkları (TiO2-O-Si-(CH2)3NH2) oluşturulmuştur. Oluşan yapıların kalite kontrol işlemleri için yüksek performanslı sıvı kromatografisi (HPLC) cihazı kullanılarak her bir sentez aşamasının HPLC analizi yapılmıştır. Fourier dönüşümlü kızıl ötesi spektrometresi (FT-IR) yöntemi ile kimyasal yapı analizleri, florimetrik analiz ile floresans özellikleri incelenmiştir. Yüzey özellikleri için taramalı elektron mikroskobu (SEM), dinamik ışık saçılımı methodu (DLS) ile yapılmıştır. I- 131, Tc- 99m, Sr- 90 ve I- 125 radyonüklidleri kullanılarak sentezi yapılan nanosistemlerin sıvı sintilatör olarak kullanılabilirliği incelenmiş ve ticari sıvı sintilatör materyali olarak kullanılan diisopropylnaphthalene ile karşılaştırılmıştır. Sonuçlar kına bitkisinden elde edilen Lawson molekülünün özellikle silikalı türevinin ve TiO2 nanoparçacıklarının silikalı türevlerinin geleneksel ticari sintilatörlere göre alternatif olabileceğini göstermiştir., The aim of this thesis is to create new liquid scintillation materials by synthesizing natural compounds and nanomaterials which can be called greener synthesis. One of the compound was Lawson diphosphate (Lawson-P), a phosphate-containing derivative of the Lawson molecule (2-hydroxy-1,4-naphthoquinone). For this purpose, the Lawson molecule, one of the main molecules of the henna (Lawsonia inermis) plant, was phosphorylated and Lawsondiphosphate (Lawson - P) was formed. In the next step, Lawson-P (LW-P-O- (Si (OH) 3) was formed, which was silicified by silica. The other system studied is TiO2 nanoparticles and their silicate and silane derivatives. TiO2 nanoparticles were synthesized, coated with silica to form TiO2 nanoparticles (TiO2-O-Si (OH)3) and silanated to form silane coated TiO2 nanoparticles (TiO2-O-Si-(CH2)3NH2). HPLC analysis of each synthesis step was performed by using high performance liquid chromatography (HPLC) equipment for quality control of the resulting structures. Fourier transformed infrared spectrometry (FT-IR) method, chemical structure analysis, fluorometric spectra were investigated. The scanning electron microscope (SEM) for surface properties was performed by dynamic light scattering method (DLS). The use of nanosystems synthesized using I-131, Tc-99m, Sr-90 and I- 125 radionuclides as liquid scintillators was investigated and compared with diisopropylnaphthalene used as commercial liquid scintillator material. The results showed that the silicon derivatives of the Lawson molecule obtained from the henna plant and the silicate derivatives of the TiO2 nanoparticles could alternatively be an alternative because they did not show toxicity with respect to conventional commercial scintillators.

As nuclear medicine community has shown an increasing interest in accelerator produced Tc-99m radionuclide, the possible alternative direct production routes for producing Tc-99m were investigated intensively. One of these accelerator production routes is based on the Mo-100(p,2n)Tc-99m reaction. The cross section of this nuclear reaction was studied by several laboratories earlier but the available data-sets are not in good agreement. For large scale accelerator production of Tc-99m based on the (100)mMo(p,2n)Tc-99m reaction, a well-defined excitation function is required to optimise the production process effectively. One of our recent publications pointed out that most of the available experimental excitation functions for the Mo-100 (p,2n)(99)mTc reaction have the same general shape while their amplitudes are different. To confirm the proper amplitude of the excitation function, results of three independent experiments were presented (Takacs et al., 2015). In this work we present results of a thick target count rate measurement of the E-gamma = 140.5 keV gamma-line from molybdenum irradiated by E-p = 17.9 MeV proton beam, as an integral benchmark experiment, to prove the cross section data reported for the Mo-100(p,2n)Tc-99m and Mo-100(p,pn)Mo-99 reactions in Takacs et al. (2015).

In this study Isoniazid (INH) as one of the first line drugs in treatment of Tuberculosis was investigated to be loaded in Solid Lipid Nanoparticles (SLNs) for reducing hepatotoxicity as well as prolonging drug release. High shear homogenization method was performed to prepare INH SLNs. To compare biodistribution of INH before and after loading in SLNs, INH was labeled by Technetium 99 (Tc99) after derivatization. The particle size of the prepared SLNs was 167 and 200 nm before and after lyophilization, respectively. Loading efficiency was calculated using the reverse method and release study was performed by using the dialysis sack method. Loading efficiency was 98%, and more than 85% of the loaded drug released in 3 h. Differential Scanning calorimeter (DSC) studies were performed for evaluating of the probability of happening hydrogen bonds or other chemical interactions between cholesterol as carrier and isoniazid as active pharmaceutical ingredient. The results could support the probability of hydrogen bond formation between cholesterol and INH. Gamma Scintigraphy studies showed that after administering INH SLNs, longer drug retention in the body was obtained compared to free INH. Quantitative gamma counting showed that the concentration of INH in the liver and intestines could be decreased by using nanotechnology.

IntroductionRadionuclides for leucocyte kinetic studies have progressed from non-gamma emitting cell-labelling radionuclides through gamma emitting nuclides that allow imaging of leucocyte kinetics, to the next goal of positron emission tomography (PET).Sources of dataMostly the authors’ own studies, following on from studies of the early pioneers.Areas of controversyFrom early imaging studies, it appeared that the majority of the marginated granulocyte pool was located in the lungs. However, later work disputed this by demonstrating the exquisite sensitivity of granulocytes to ex vivo isolation and labelling, and that excessive lung activity is artefactual.Areas of agreementFollowing refinement of labelling techniques, it was shown that the majority of marginated granulocytes are located in the spleen and bone marrow. The majority of leucocytes have a pulmonary vascular transit time only a few seconds longer than erythrocytes. The minority showing slow transit, ~5% in healthy persons, is increased in systemic inflammatory disorders that cause neutrophil priming and loss of deformability. Using a range of imaging techniques, including gamma camera imaging, whole-body counting and single photon-emission computerized tomography, labelled granulocytes were subsequently used to image pulmonary trafficking in lobar pneumonia, bronchiectasis, chronic obstructive pulmonary disease and adult respiratory distress syndrome.Growing pointsMore recently, eosinophils have been separated in pure form using magnetic bead technology for the study of eosinophil trafficking in asthma.Areas timely for developing researchThese include advancement of eosinophil imaging, development of monocyte labelling, development of cell labelling with PET tracers and the tracking of lymphocytes.

Use of highly-enriched uranium (HEU) at research reactors or the exporting of HEU for humanitarian purposes, such as for the production of medical isotopes, leads to a risk of nuclear proliferation. This thesis will discuss efforts to improve the understanding of low-enriched uranium (LEU) to enable more accurate predictions of the material behavior during manufacturing and use as an irradiation target for the production of medical isotope Tc-99m and as a reactor fuel. The α-phase (orthorhombic crystal structure) LEU foils proposed for use in the production of medical isotope Tc-99m have anisotropic properties due to the crystallographic texture which is introduced during the foil rolling process. This was previously demonstrated using physics-based viscoplastic self-consistent (VPSC) modeling, which used the deformation-induced texture as an input [1]. A phenomenological, analytical model for the anisotropic yield stress behavior of orthotropic, hexagonal metals was developed by Cazacu, Plunkett, and Barlat [2], denoted CPB06. A MATLAB optimization routine was used to determine values for the anisotropy coefficients used in the model, by fitting to the VPSC predictions. CPB06 was implemented as a user-subroutine (VUMAT) in ABAQUS/Explicit, a commercial finite element analysis (FEA) software, which allowed for finite element simulation of the irradiation target manufacturing process. FEA simulations ultimately revealed that while the plastic anisotropy of the foil could potentially change the strength of the material relative to the isotropic case under certain loading conditions, anisotropy did not noticeably affect the foil strength when under internal pressure, and the performance of the Tc-99m target was not affected. The -phase stabilized LEU-10Mo (wt%) alloy has been identified as a candidate fuel for high performance research reactors, though there are concerns regarding phase and mechanical stability under reactor conditions, especially during transient conditions. In-situ neutron diffraction performed at the Los Alamos Neutron Science Center (LANSCE) was used to investigate phase decomposition behavior in U-10Mo and U-9.8Mo with 0.2 wt% ternary additions of Cr, Ni, or Co, thus maintaining the total alloy content in all four alloys at 10 wt%. Since the metastable BCC phase γ-U is optimal, it is critical to understand whether or not such alloying additions delay or promote phase decomposition. These alloying additions were chosen for research since they are readily available, and come in different unit-cell structures (BCC, FCC, and HCP). During the in-situ experiments performed on the Spectrometer for Materials Research at Temperature and Stress (SMARTS), the samples were first heated at a rate of 50 ºC/min to ~650 ºC, which is above the γ-phase solvus line, and held for 1 hour to dissolve any fine, second phase particles which may have precipitated during prior heating and homogenization steps. Then, the samples were cooled at a rate of 50 ºC/min to the isothermal hold temperatures of interest, 490 or 500 ºC, and held for 20 hours to observe the kinetics of decomposition of the metastable γ-U-Mo phase toward the equilibrium α-U and γ’ (U2Mo) phases. Finally, the samples were cooled to room temperature at a rate of 50 ºC and remeasured ex-situ, both in SMARTS and in the High Intensity Pressure and Preferred Orientation (HIPPO) instrument. Rietveld analysis using the GSAS-II and MAUD software packages was employed to determine the phase fractions, lattice parameters, and crystallographic texture of all the observed phases. Experiments conducted on U-10Mo and U-9.8Mo-0.2Cr did not exhibit measurable phase decomposition. However, some phase evolution was observed in the U-9.8Mo-0.2Ni and U-9.8Mo-0.2Co alloys, which included development of the orthorhombic α-U phase along with a corresponding molybdenum-rich, and perhaps ordered, version of the BCC γ-phase, here denoted γb. Hence, it is concluded that Ni and Co ternary additions degrade the thermal stability of U-10Mo, while Cr additions do not have an observable effect. It is hypothesized that the more rapid phase evolution in the Ni and Co containing alloys is due to heterogeneous nucleation associated with the presence of small grain boundary precipitate phases, including U6Co and U6Ni, which were previously observed by SEM [3], and whose presence is corroborated by the presence of a small, solitary neutron diffraction peak in the experiments performed on U-9.8Mo-0.2Co.

The purpose of this study was to compare the physical characteristics of Low Energy High Resolution (LEHR), Low Energy Ultra High Resolution (LEUHR) and Medium Energy Low Penetration (MELP) collimators for simultaneous Tc-99m and I-123 imaging. MELP collimator performed well with I-123 high-energy gamma photons, but low resolution makes it unsuitable to use for acquisition of small structures such as parathyroid adenomas. LEUHR collimators optimized for Tc-99m have highest resolution, but the differences in septal penetration and sensitivity in favor of LEHR collimator needs to be tested with specific parathyroid phantoms.

WOS: 000429197900010, In the present article, we focused on the radiolabeling and evaluation of Tc-99m-TMH complex as a potential candidate for infection imaging in vivo. For this; Trimethoprim (TMH) used to treat bacterial infections was investigated to label with Tc-99m. Labeling was performed using thin (II) chloride as a reducing agent at room temperature for 1 h and radiochemical analysis involved thin layer radiochromatography (TLRC) and high pressure liquid radiochromatograpy (HPLRC) methods. The stability of labeled antibiotic was checked in the presence of rat blood serum at 37 degrees C up to 180 min. The maximum radiolabeling yield was found to be 96 +/- 2% and remained constant at more than 85 +/- 1% even in rat serum for 180 min after radiolabeling. Static image of Tc-99m-TMH in male rats demonstrated that important radiation signals are present in the infected site at first glance in 30 min. After 30 min the uptake of the Tc-99m-TMH as ID/g% in the infected muscle (INM) and normal muscle (NM) of the rats were 7.5 +/- 1.5% and 5.00 +/- 1.2%, respectively. In the INM/NM ratio a desirable behavior was observed as the values for the INM/NM increased up to 10.6. Tc-99m-TMH prepared with high yield is able to localize well in the bacterially infected muscle of the rats. As a result, Tc-99m-TMH may be developed as a radiopharmaceutical agent to distinguish infection from inflammation by nuclear imaging., Manisa Celal Bayar University Research Fund [2015-101], The authors are thankful for the financial support from the Manisa Celal Bayar University Research Fund (Contract No. 2015-101).

Epidermal growth factor receptor (EGFR) is overexpressed in a number of cancers and is the molecular target for several anti-cancer therapeutics. Radionuclide molecular imaging of EGFR expression should enable personalization of anti-cancer treatment. Affibody molecule is a promising type of high-affinity imaging probes based on a non-immunoglobulin scaffold. A series of derivatives of the anti-EGFR affibody molecule ZEGFR:2377, having peptide-based cysteine-containing chelators for conjugation of 99mTc, was designed and evaluated. It was found that glutamate-containing chelators Gly-Gly-Glu-Cys (GGEC), Gly-Glu-Glu-Cys (GEEC) and Glu-Glu-Glu-Cys (EEEC) provide the best labeling stability. The glutamate containing conjugates bound to EGFR-expressing cells specifically and with high affinity. Specific targeting of EGFR-expressing xenografts in mice was demonstrated. The number of glutamate residues in the chelator had strong influence on biodistribution of radiolabeled affibody molecules. Increase of glutamate content was associated with lower uptake in normal tissues. The 99mTc-labeled variant containing the EEEC chelator provided the highest tumor-to-organ ratios. In conclusion, optimizing the composition of peptide-based chelators enhances contrast of imaging of EGFR-expression using affibody molecules. Electronic supplementary material The online version of this article (10.1007/s00726-018-2571-1) contains supplementary material, which is available to authorized users.

Purpose: Vitamin B12 (cyanocobalamin, Cbl) is accumulated by rapidly replicating prokaryotic and eukaryotic cells. We investigated the potential of a Tc-99m labelled Cbl derivative ([99mTc]PAMA(4)-Cbl) for targeting infections caused by Escherichia coli and Staphylococcus aureus. In vitro binding assays were followed by biodistribution studies in a mouse model of foreign body infection. Procedures: E. coli (ATCC 25922) and S. aureus (ATCC 43335) were used as test strains. [57Co]Cbl, [67Ga]citrate and [99mTc]DTPA served as reference compounds. The in vitro competitive binding of [57Co]Cbl or [99mTc]PAMA(4)-Cbl, and unlabeled Cbl, to viable or killed bacteria, was evaluated at 37 and 4 °C. A cage mouse model of infection was used for biodistribution of intravenous [57Co]Cbl and [99mTc]PAMA(4)-Cbl in cage and dissected tissues of infected and non-infected mice. Results: Maximum binding (mean ± SD) of [57Co]Cbl to viable E. coli was 81.7 ± 2.6 % and to S. aureus 34.0 ± 6.7 %, at 37 °C; no binding occurred to heat-killed bacteria. Binding to both test strains was displaced by 100- to 1000-fold excess of unlabeled Cbl. The in vitro binding of [99mTc]PAMA(4)-Cbl was 100-fold and 3-fold lower than the one of [57Co]Cbl for E. coli and S. aureus, respectively. In vivo, [99mTc]PAMA(4)-Cbl showed peak percentage of injected dose (% ID) values between 1.33 and 2.3, at 30 min post-injection (p.i.). Significantly higher retention occurred in cage fluids infected with S. aureus at 4 h and with E. coli at 8 h p.i. than in non-infected animals. Accumulation into infected cages was also higher than the one of [99mTc]DTPA, which showed similar biodistribution in infected and sterile mice. [57Co]Cbl gradually accumulated in cages with peaks % ID between 3.58 and 4.83 % achieved from 24 to 48 h. Discrimination for infection occurred only in E. coli-infected mice, at 72 h p.i. [67Ga]citrate, which showed a gradual accumulation into cage fluids during 12 h, was discriminative for infection from 48 to 72 h p.i. (P, Molecular Imaging and Biology, 17 (6), ISSN:1860-2002, ISSN:1536-1632

In the present work, we investigated potential means to obtain neutral tricarbonyl mixed-ligand fac-[M(CO)(3)(LL2)-L-1] complexes (M = Re, Tc-99m) containing the (2-hydroxyphenyl)diphenylphosphine (POH) bidentate ligand ((LH)-H-1) and a series of monodentate ligands (L-2). First, fac[Re(CO)(3)(PO)(H2O)], 1, was synthesized by reaction of POH and [Et4N](2)[Re(CO)(3)Br-3] in equimolar amounts in MeOH at room temperature. Interestingly, with excess of POH this reaction afforded fac-[Re(CO)(3)(PO)(POH)], 2, with POH operating both as a bidentate and as a monodentate ligand. Owing to the presence of the labile aqua ligand, which can be readily replaced by various monodentate ligands, 1 was further used as a precursor to generate a small library of the desired fac-[M(CO)(3)(LL2)-L-1] complexes. Specifically, by reaction of triphenylphosphine (PPh3), imidazole (im), pyridine (py), cyclohexyl isocyanide (cisc), and tert-butyl isocyanide (tbi), the following products were readily obtained in excellent yields (92%-95%): fac-[Re(CO)(3)(PO)(PPh3)], 3, fac-[Re(CO)(3)(PO)(im)], 4, fac-[Re(CO)(3)(PO)(py)], 5, fac-[Re(CO)(3)(PO)(CiSc)], 6, and fac-[Re(CO)(3)(PO)(tbi)], 7. All compounds were fully characterized by elemental analysis, IR and NMR spectroscopies, and electrospray ionization(+) mass spectrometry. Their solid-state structure was elucidated by X-ray crystallography. Of considerable interest is the fact that the corresponding 2'-7' were easily accessible at the Tc-99m-tracer level in quantitative yields after reaction of POH and the respective monodentate ligand L-2 with fac-[Tc-99m(CO)(3)(H2O)(3)] in aqueous MeOH, as verified by comparative chromatographic methods adopting dual photo and radiometric detection modes. The high stability displayed by all Tc-99m complexes during histidine and cysteine challenge assays underscored the suitability of the fac-[M(CO)(3)(PO)L-2] system for radiopharmaceutical development purposes.

Background Image-based measurement of absorbed dose of Ra-223 dichloride may be useful in predicting therapeutic outcome in patients with castration-resistant prostate cancer (CRPC). In general, SPECT has been found to be more accurate than planar imaging in terms of lesion-based analysis. The aims of this study were to assess the feasibility and clinical usefulness of Ra-223 SPECT. The energy spectrum of Ra-223 and SPECT images of a cylindrical phantom with a hot rod were obtained to determine the collimator candidates and energy window settings suitable for clinical Ra-223 SPECT (basic study A). Another phantom with a tube-shaped chamber and two spheres simulating bowel activity and metastatic lesions in the lumbar spine was scanned with medium-energy general-purpose (MEGP) and high-energy general-purpose (HEGP) collimators (basic study B). Ten patients with CRPC underwent SPECT imaging 2 h after Ra-223 injection successively with MEGP and HEGP collimators in random order for 30 min each. Lesion detectability and semi-quantitative analyses of bone metastasis (i.e. lesion-to-background ratio (LBR)) were performed compared to Tc-99m HMDP SPECT. Results Basic study A revealed that an 84-keV photopeak ± 20% using the HEGP collimator offers better SPECT image quality than the other imaging conditions. Basic study B showed that uptake in one of the spheres was overestimated by overlapped activity of the tube-shaped chamber in planar imaging whereas the spheres had similar counts and significantly higher sphere-to-background ratio in SPECT. On both planar and SPECT images, HEGP gave higher image contrast than MEGP (p

Radiolabeled amino acids as metabolic tracers are increasingly important for imaging and therapy applications. There are only a few reports on Tc-99m-labeled amino acids that have been evaluated in vivo. In this work we coupled a small and highly potent chelator for the fac-[Tc-99m(CO)(3)](+) core to Ltyrosine through a poly(ethylene glycol) linker and investigated the in vivo biodistribution of the Tc-99m-labeled L-tyrosine derivative. In vivo evaluation and biodistribution in mice bearing C6tumor xenografts revealed little tumor and pancreas uptake. The microSPECT images showed rapid clearance from the blood pool. Fast uptake into the gallbladder and an extended residence time makes this labeled tyrosine suitable for gallbladder imaging and associated dysfunctions.

Las moléculas heterobivalentes radiomarcadas han mostrado ser una estrategia adecuada para obtener imágenes del tumor de manera sensible, específica y no invasiva debido a que interactúan concomitantemente con diferentes blancos moleculares sobre la célula tumoral. Una de las características fenotípicas de las células de cáncer de mama es la sobre-expresión de receptores de membrana que regulan el comportamiento celular. Entre estos receptores se encuentran el receptor del péptido liberador de gastrina (GRPR) y el receptor de folatos (FR), los cuales al unirse con alta afinidad a la Bombesina y ácido fólico/folato respectivamente, producen respuestas celulares que favorecen el crecimiento y proliferación celular. El objetivo del presente trabajo fue sintetizar y caracterizar químicamente los conjugados heterobivalentes Lys1(α,γ-folato)Lys3(99mTc-HYNIC)-Bombesina (1-14) y Lys1(α,γ-folato)Lys3(177Lu-DOTA)-Bombesina (1-14), con la finalidad de evaluar tanto in vitro como in vivo su potencial como radiofármacos heterobivalentes para diagnóstico y/o tratamiento de células de cáncer de mama +GRPR y +FR. Adicionalmente, se evaluó el potencial de Lys1(α,γ-folato)Lys3(99mTc-HYNIC)-Bombesina (1-14) para medir la actividad metabólica de dichas células a través de imágenes SPECT. Para obtener a los conjugados Lys1(α,γ-folato)Lys3(HYNIC)-Bombesina (1-14) y Lys1(α,γ-folato)Lys3(DOTA)-Bombesina (1-14), los péptidos Lys1Lys3(HYNIC)-Bombesina (1-14) y Lys1Lys3(DOTA)-Bombesina (1-14) se conjugaron a ácido fólico mediante un enlace amida. Los productos se purificaron por HPLC de exclusión molecular y se caracterizaron por espectroscopia UV-Vis, IR-FT y espectrometría de masas MALDI-TOF. El radiomarcado de Lys1(α,γ-folato)Lys3(HYNIC)-Bombesina (1-14) con 99mTc se realizó con EDDA/tricina como coligantes y SnCl2 como agente reductor. Para el radiomarcado de Lys1(α,γ-folato)Lys3(DOTA)-Bombesina (1-14) con 177Lu, se utilizó 177LuCl3 diluido con buffer de acetato 1 M a pH=5. La pureza radioquímica se evaluó en un HPLC en fase reversa. Se evaluó la estabilidad de los conjugados heterobivalentes Lys1(α,γ-folato)Lys3(99mTc-HYNIC)-Bombesina (1-14) y Lys1(α,γ-folato)Lys3(177Lu-DOTA)-Bombesina (1-14) en suero humano. Se determinó la afinidad de los conjugados heterobivalentes a la proteína recombinante GRPR y a la proteína humana FR. La captación in vitro se evaluó en células de cáncer de mama T47D (+GRPR y +FR). La biodistribución y captación en el tumor se determinaron en ratones atímicos con tumores inducidos T47D. Para evaluar la especificidad de los conjugados heterobivalentes, tanto en los estudios in vitro como in vivo se bloquearon los receptores GRPR y FR. Los estudios de imagen en ratones atímicos con tumores T47D se obtuvieron con un micro-SPECT/CT. La actividad metabólica del tumor se determinó a partir de imágenes SPECT/CT utilizando Lys1(α,γ-folato)Lys3(99mTc-HYNIC)-Bombesina (1-14) y se comparó con 18F-FDG y 99mTc-Folato. Se estimó la dosis absorbida en el tumor, riñón, hígado y páncreas a partir de la actividad acumulada en la región de interés. Los resultados obtenidos en los estudios in vitro e in vivo se compararon con sus respectivos monómeros Lys1Lys3(99mTc-HYNIC)-Bombesina (1-14) y Lys1Lys3(177Lu-DOTA)-Bombesina (1-14). Los estudios espectroscópicos y el análisis por HPLC indicaron que los conjugados heterobivalentes se obtuvieron con alta pureza química y alta pureza radioquímica (>95%). Los conjugados heterobivalentes Lys1(α,γ-folato)Lys3(99mTc-HYNIC)-Bombesina (1-14) y Lys1(α,γ-folato)Lys3(177Lu-DOTA)-Bombesina (1-14) mostraron alta estabilidad en suero humano con 2% de unión a proteínas a las 2 h de incubación. Ambos conjugados mostraron alta afinidad a la proteína recombinante del GRPR y a la proteína humana del RF. Los estudios in vitro mostraron que los conjugados heterobivalentes tienen reconocimiento específico a las células de cáncer de mama T47D +GRPR y +FR, y mostraron un incremento en la captación debido al efecto concomitante entre la unión Bombesina-GRPR- y Folato-FR. Los estudios de biodistribución de los conjugados heterobivalentes en ratones atímicos con tumores inducidos T47D, mostraron alta captación en el tumor con alto contraste en las imágenes SPECT/CT. Lys1(α,γ-folato)Lys3(99mTc-HYNIC)-Bombesina (1-14) permitió evaluar a través de imagen la actividad metabólica del tumor. El compuesto Lys1(α,γ-folato)Lys3(177Lu-DOTA)-Bombesina (1-14) mejoró la dosis absorbida al tumor debido a la unión concomitante de Bombesina-GRPR y Folato-FR. Este estudio demostró que los conjugados heterobivalentes Lys1(α,γ-folato)Lys3(99mTc-HYNIC)-Bombesina (1-14) y Lys1(α,γ-folato)Lys3(177Lu-DOTA)-Bombesina (1-14) mejoran la detección de células de cáncer de mama +GRPR y +FR, por lo que, pueden ser utilizados para el diagnóstico y/o tratamiento de tumores de mama que sobre-expresan GRPR y FR. Financiamiento CONACYT (CONACYT-SEP-CB-2014-01-242443)

Симултано поткожно инјектирање на Ј-131 и Tc-99m во трасерски количини на стаорци, покажува во три случаи еднаков тиреоиден клиренс за двата радиоизотопа, но во два случаи се прикажува разлика.Клиренс студиите со Ј-131 и Tc-99m поради различната динамика на концентрација во раната „анорганска фаза“ во тиреоидеата, покажа дека не се изводливи. Најверојатно Tc-99m во тек на транспортот од поткожното ткиво до тироцитите претрпува промена во смисол на евентуална редукција, што може да ја промени динамиката на тироидниот аптејк.Подкожниот пат на администрација на Tc-99m не обезбедува еднакв клиренс на Ј-131 во тироидеата и за физиолошки студии Tc-99m може да даде погрешни резултати., Thyroid clearance of J-131 and Tc-99m after simultaneous subcutaneous injection in rats were estimated in the early phase. Arterial blood samples were drawn with a polyethene catheter inserted in the iliac artery in intervals of two minutes. The animals were sacrificed at the 20th minute and the wet weight of the thyroid gland was estimated. Tc-99m activity was counted on a ring counter consisting of GM tubes. The activity of J-131 was measured after the decay of Tc-99m. On and Tc-99m were identical which suggests that the subcutaneous way of Tc-99m application alters the pertechnetate state of the compound very similar to the oral route of Tc-99m pertechnetate application.

WOS: 000388115200003, Peptide radiopharmaceuticals have an increasing significance in nuclear medicine practice. beta-casomorphin is a digestive peptide with 6 amino acids (Tyr-Pro-Phe-Pro-Gly-Pro). N terminal amino acid chain mainly tyr-pro-phe-pro structured exogen opioid peptid type beta cosomorphin are beta-receptor agonistic activity with priority. Animal studies show that beta-casomorphins can act as opioid receptor agonists. The aim of this study was to label beta-casomorphin with (99m) Tc and to examine its usefulness as an opioid receptor binding radiopharmaceutical in Albino Wistar rats and cancer cells. beta-casomorphin was labeled with (99m) Tc radionuclide using bifunctional chelating agent. Quality control studies were done by Instant Thin layer chromatography (ITLC) and High performance liquid chromatography (HPLC) methods. Binding efficiency of the compound was more than 99%. It was observed as stable for at least 3 h at room temperature. Lipophilicity was also performed for labeled molecule. Imaging studies for (99m) Tc labeled molecule was done in rats by using gamma camera. For biodistribution studies; (99m) Tc labeled molecule was injected to the rats from tail vein and radioactivity per gr weight of each organ was measured as count per second (cps). Receptor specificity was evaluated in imaging and biodistribution studies in experimental animals. Cell labeling studies were also performed on breast and ovarien cancer cells. In terms of evaluating the biodistribution of (99m) Tc-beta-casomorphin molecule in rats, uterus and ovary displayed high involvement. It was also confirmed by cell labeling studies. If the radiopharmaceutical is radiolabeled with therapeutic radionuclides it would be useful for therapy for uterus, ovary and breast tumors., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TBAG-104T241], This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK), the author wish to thank TUBITAK for financial support (Grant No: TBAG-104T241).

A general procedure for the preparation of a new class of neutral six-coordinated mixed ligand [Tc-99m(III)(PS)(2)(Ln)] compounds (PS = trisalkyl-phosphino-thiolate; Ln = dithiocarbamate) is reported as well as their in vitro stability and the ex vivo tissue distribution studies. [Tc-99m(PS)(2)(Ln)] complexes were prepared in high yield in nearly physiologic conditions following a one-pot procedure. For instance, the chemical identity of [Tc-99m(PSiso)(2)(L1)] (PSiso = 2-(diisopropylphosphino)ethanethiol; L1 = pyrrolidine dithiocarbamate) was determined by HPLC comparison with the corresponding (99g)Tc-complex. All complexes comprise the stable [Tc-99m(III)(PS)(2)](+) moiety, where the remaining two coordination positions are saturated by a dithiocarbamate chelate, also carrying bioactive molecules (e.g., 2-methoxyphenylpiperazine). [Tc-99m(PS)(2)(Ln)] complexes were inert toward ligand exchange reactions. No significant in vitro and in vivo biotransformation were observed, underlining their remarkable thermodynamic stability and kinetic inertness. These results could be conveniently utilized to devise a novel class of Tc-99m(III)-based compounds useful in radiopharmaceutical applications.

Summary Background Although specificity of SPECT/CT examination using technetium-99m radiolabeled red blood cells (Tc-99m-RBC) for detection of liver hemangiomas is very high, it is still not perfect. It is possible to overlook a malignancy. Moreover, the difference in accumulation of RBCs between a hemangioma and uninvolved liver remains unknown. The aim of the study is to determine the quotients of accumulation of Tc-99m-RBC in hemangiomas and in normal liver parenchyma (HEM/liv), and to verify, whether the quotient could be potentially helpful in distinguishing hemangiomas from other RBC-accumulating liver masses. Material/Methods 34 liver lesions larger than 1.5 cm classified scintigraphically (qualitatively) in our Department as either typical or suspicious of hemangioma 1.5–4 years earlier were enrolled in this retrospective study. Their SPECT/CT images were acquired 1 hour after in vivo labeling of RBCs with Tc-99m. In reconstructed images, ellipsoidal regions of interest (ROIs) with diameters of about 1.5 cm were created in the assessed lesions (HEM) and in the uninvolved liver parenchyma (liv). The HEM/liv quotients were calculated for each mass. The results were compared with radiological data. Results 31 lesions were found to be clinically and radiologically typical for hemangiomas, their HEM/liv ratios were at least 1.6 (smaller masses) or 1.8 (larger masses). One lesion with HEM/liv ratio equal to 1.21 was classified as metastasis. Two lesions with HEM/liv 1.42 and 1.46 were classified as benign foci other than hemangioma. Conclusions The quantitative analysis can be preliminarily proposed as a helpful tool in the assessment of possible liver hemangiomas.

Bu çalışmada, paklitaksel (PTX) yüklü katı lipid nanoparçacıklar sentezlenerek teknesyum-99m (I) trikarbonil koru ile radyoişaretlenmesi ve bu yapının biyolojik davranışının in vivo ve in vitro olarak incelenmesi amaçlanmıştır. Solvent difüzyon yöntemi ile hazırlanan katı lipid nanoparçacıkların (SLN) yapısal özellikleri Zeta Potansiyeli Analizi, Dinamik Işık Saçılımı (DLS) yöntemi, Geçirimli Elektron Mikroskobu (TEM) ve Taramalı Elektron Mikroskobu (SEM) görüntüleri ile tanımlanmıştır. Reseptör hedefleme amacıyla nanoparçacıklar, sentezlenen folat polietilen glikol-kolesterol hemisüksinat (Fol-PEG-CHEMS) molekülü ile modifiye edilmiştir. Hedefleyici molekülün karakterizasyonu proton nükleer manyetik rezonans (1H-NMR) spektroskopisi ile belirlenmiştir. Paklitaksel yüklü katı lipid nanoparçacıkların (SLN-PTX) teknesyum-99m (I) trikarbonil koru, [99mTc(CO)3(H2O)3]+, ile % 90 verimle radyoişaretlenmesi sağlanmıştır. Paklitaksel yüklü radyoişaretli katı lipid nanoparçacıkların (99mTc(CO)3-SLN-PTX) kalite kontrol çalışmaları İnce Tabaka Radyo Kromatografi (TLRC) ve Yüksek Performanslı Sıvı Radyokromatografi (HPLRC) yöntemleri kullanılarak gerçekleştirilmiştir. 99mTc(CO)3-SLN-PTX'in biyolojik davranışının in vitro yöntemle belirlenmesi amacıyla folat reseptörü pozitif olan folat reseptörü pozitif MCF7 meme (adenokarsinoma) epiteli ve HeLa serviks (adenokarsinoma) epiteli ile folat reseptörü negatif A549 akciğer (karsinoma) epitellerinden oluşan kanser hücre hatları üzerinde inkorporasyon çalışmaları gerçekleştirilmiştir. 99mTc(CO)3-SLN-PTX'in MCF7 ve HeLa hücreleri üzerinde A549 hücrelerine kıyasla daha yüksek bağlanma verimine sahip olduğu görülmüştür. 99mTc(CO)3-SLN-PTX'in in vivo biyolojik davranışının belirlenmesi amacıyla sağlıklı dişi Wistar Albino sıçanlar üzerinde biyodağılım ve görüntüleme çalışmaları gerçekleştirilmiştir. Biyodağılım ve görüntüleme çalışmaları sonucunda 99mTc(CO)3-SLN-PTX'in folat reseptörü bulunduran böbrek dokusunda diğer bölgelere göre daha fazla tutuluma sahip olduğu gözlenmiştir. In vitro ve in vivo çalışmalar sonucunda elde edilen verilerden geliştirilen sistemin (paklitaksel yüklü radyoişaretli katı lipid nanoparçacıkların) folat reseptörlerine karşı spesifiteye sahip olduğu görülmektedir. Geliştirilen paklitaksel yüklü radyoişaretli katı lipid nanoparçacıkların hazırlanması kolay, hedefe yönelik, biyouyumlu ve terapi potansiyeline sahip bir teşhis ajanı geliştirilmesine katkı saylayacağı düşünülmektedir., In current study, it is aimed to synthesize paclitaxel (PTX) loaded solid lipid nanoparticles, to radiolabel these nanoparticles with technetium-99m tricarbonyl core and to evaluate its biological behaviour utilizing in vitro and in vivo methods. Solid lipid nanoparticles (SLN) were synthesized by solvent diffusion method. Structural characterization of SLN was performed by Zeta Potential Analysis, Dynamic Light Scattering (DLS) method, Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM) imaging. Nanoparticles were modified with folate derivative polyethylene glycol-cholesterol hemisuccinate (Fol-PEG-CHEMS) molecule to target folate receptors. Characterization of targeting molecule was performed by proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR). Radiolabeling of PTX loaded solid lipid nanoparticles with technetium (I) tri carbonyl core [99mTc(CO)3(H2O)3]+ accomplished with 90 % efficiency. Thin Layer Radiochromatography (TLRC) and High Performance Liquid Radiochromatography (HPLRC) methods were used for quality control of paclitaxel loaded radiolabeled solid lipid nanoparticles (99mTc(CO)3-SLN-PTX). In vitro biological behavior of 99mTc(CO)3-SLN-PTX investigated with incorporation studies on folate receptor positive breast (MCF7), cervix (HeLa) and folate receptor negative lung (A549) carcinoma cell lines. Higher uptake values of 99mTc(CO)3-SLN-PTX were determined on MCF7 and HeLa cell lines according to A549 cell line. Biodistribution and imaging studies were conducted to investigate in vivo behaviour of 99mTc(CO)3-SLN-PTX on female Wistar Albino rats. According to results of in vivo studies, it was observed that 99mTc(CO)3-SLN-PTX have higher uptake in folate receptor positive kidney tissue considering other sites. According to obtained data from in vitro and in vivo studies, it is seen that the improved system (paclitaxel loaded radiolabeled solid lipid nanoparticles) is specific to folate receptors. It is concluded that the system improved in present study will make contribution to improve an easy prepared, target specific and biocompatible diagnostic agent with therapy potential.

The purpose of this study was to evaluate the effect of cyclization on the biological profile of a [ 99m Tc(N)(PNP3)]-labeled α-melanocyte stimulating hormone peptide analog. A lactam bridge-cyclized H-Cys-Ahx-βAla 3 -c[Lys 4 -Glu-His-D-Phe-Arg-Trp-Glu 10 ]-Arg 11 -Pro-Val-NH 2 (NAP―NS2) and the corresponding linear H-Cys-Ahx-βAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH 2 (NAP―NS1) peptide were synthetized, characterized by ESI-MS spectroscopy and their melanocortin-1 receptor (MC1R) binding affinity was determined in B16/F10 melanoma cells. The consistent [ 99m Tc(N)(PNP3)]-labeled compounds were readily obtained in high specific activity and their stability and biological properties were assessed. As an example, the chemical identity of [ 99m Tc(N)(NAP–NS1)(PNP3)] + was confirmed by carrier added experiments supported by radio/UV HPLC analysis combined with ESI(+)-MS. Compared with the linear peptide, cyclization negatively affected the biological properties of NAP–NS2 peptide by reducing its binding affinity for MC1R and by decreasing the overall excretion rate of the corresponding [ 99m Tc(N)(PNP3)]-labeled peptide from the body as well as its in vivo stability. [ 99m Tc(N)(NAP–NS1)(PNP3)] + was evaluated for its potential as melanoma imaging probe in murine melanoma model. Data from in vitro and in vivo studies on B16/F10 melanoma model of [ 99m Tc(N)(NAP–NS1)(PNP3)] + clearly evidenced that the radiolabeled linear peptide keeps its biological properties up on the conjugation to the [ 99m Tc(N)(PNP3)]-building block. The progressive increase of the tumor-to-nontarget ratios over the time indicates a quite stable interaction between the radio-complex and the MC1R.

Visilizumab is an IgG(2) humanized monoclonal antibody (mAb) characterized by non-Fc gamma R binding and specific to the CD3 antigen, expressed on more than 95% of circulating resting T-lymphocytes and on activated T-lymphocytes homing in inflamed tissues. We hypothesized that the use of a radiolabeled anti-CD3 antibody might serve as a diagnostic tool for imaging T-cell traffic and lymphocytic infiltration of tissues and organs affected by autoimmune diseases. Here we describe the results of in vitro and animal experiments with (99m)Tc-succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH)-visilizumab. Methods: For mAb labeling, we used a 2-step method with a heterobifunctional linker SHNH. Several titrations were performed to obtain the best labeling efficiency. In vitro quality controls included stability assay, cysteine challenge, sodium dodecyl sulfate polyacrylamide gel electrophoresis, binding assay, and immunoreactivity assay. In vivo studies by high-resolution images were performed at 6 and 24 h after the injection of (99m)Tc-SHNH-visilizumab. These included cell-targeting experiments in BALB/c mice xenografted subcutaneously with an increasing number of HuT78 cells in the leg and displaced with an excess of cold antibody. We also studied irradiated severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells (hPBMCs) and injected with (99m)Tc-labeled visilizumab or control mAb. After dynamic imaging for 3 h, major organs were removed, counted, and processed for immunohistologic examination. Results: Visilizumab was labeled with HYNIC with high labeling efficiency (>90%) and high specific activity (SA; 10,360-11,100 MBq/mg), with retained biochemical integrity and in vitro binding activity to CD3-positive cells. The in vivo targeting experiment showed a proportional increase of specific uptake with the number of injected cells, both at 6 and at 24 h, and the in vivo competition study demonstrated more than 60% decreased uptake after an excess of unlabeled antibody. In SCID mice, hPBMCs in different tissues were detected by (99m)Tc-labeled visilizumab and confirmed by histology. Conclusion: Visilizumab can be efficiently labeled with (99m)Tc with high efficiency and SA and could be a valuable tool for the study of human T-lymphocyte trafficking and lymphocytic infiltration of tissues and organs.

O autor faz uma breve revisão dos avanços da cardiologia nuclear na avaliação da perfusão miocárdica na última década. O desenvolvimento de técnicas que corrigem para atenuação de tecidos moles permitiu um incremento dos valores de especifidade no diagnóstico da doença arterial e coronariana e na determinação da viabilidade miocárdica. Igualmente, o emprego de métodos quantitativos permitiu melhorar, ainda mais, a confiabilidade do método, bem como sua reprodutibilidade. Finalmente, a obtenção de dados funcionais de função ventricular juntamente com as informações de perfusão têm permitido obter importantes dados para o diagnóstico e, principalmente, a estratificação de risco na doença arterial coronariana.

The Tc-99m-labelling of the amino acids tyrosine (Tyr) and lysine (Lys), fundamental building blocks of proteins and peptides, as well as biological properties of the labelled compounds are investigated. Three different approaches for the labelling with Tc-99m have been investigated: direct reduction with stannous tin in the presence of the amino acids, the preformed chelate approach through polydentate chelates DTPA and GH, and the organometallic approach using [Tc-99m(CO)(3)(H2O)(3)](+) precursor. The direct labelling approach was not successful and the yield was poor. In the presence of DTPA and GH, the labelling efficiency was between 43.6 and 97.8%, depending on the amino acid and the polydentate chelate. The use of [Tc-99m(CO)(3)(H2O)(3)](+) precursor point at the formation of Tc-99m(l) co-ordinated complexes with high yield. In this approach, pH and heating influenced the yields. The results of organ distribution study for [Tc-99m(Tyr)(H2O)(CO)(3)] and [Tc-99m(Lys)(H2O)(CO)(3)] show accumulation in liver, kidneys and intestine., Copyright (C) 2007 John Wiley and Sons, Ltd.

The nuclear medicine community has been expressing concerns world wide regarding shortages of Tc-99m supply based on fission production of Mo-99 from highly enriched uranium (HEU) to prepare Mo-99/Tc-99m generators. As an alternative to reactor produced Mo-99/Tc-99m generator technology, the direct production of Tc-99m on accelerators is considered. There are a number of methods of using accelerators to produce Tc-99m and/or Mo-99. Direct production of Tc-99m on highly enriched Mo-100 target using cyclotrons is interesting for energies up to 20 MeV, so as to minimize the impurities from additional open reaction channels. To estimate the quality of the accelerator produced Tc-99m all the possible reaction routes should be mapped which could be potentially involved in this technology. However, a well defined excitation function for the Mo-100(p,2n)Tc-99m primary reaction is needed, in order to achieve acceptable good results in assessing the quality of the accelerator-produced Tc-99m by theoretical calculations. Most of the available experimental cross section data series for the Mo-100(p,2n)Tc-99m reaction have the same general shape while their amplitudes are different. A large difference more than a factor of two may, indeed, be observed between the lowest and the highest datasets values. The aim of this study was therefore to get a new evaluation for the Mo-100(p,2n)Tc-99m cross section, through three independent experiments, aiming at a more confident estimation about the amplitude of the excitation function. (C) 2015 Elsevier B.V. All rights reserved.