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H 4 pypa is a nonadentate nonmacrocyclic chelator, which previously demonstrated high affinity for scandium-44, lutetium-177, and indium-111. Herein, we report the highly stable binary [Zr(pypa)] complex; the nonradioactive complex was synthesized and characterized in detail using high-resolution electrospray-ionization mass spectroscopy (HR-ESI-MS) and various nuclear magnetic resonance spectroscopies (NMR), which revealed C 2 v symmetry of the complex. The geometry of [Zr(pypa)] was further detailed via X-ray crystallography and compared with the structure of [Fe(Hpypa)]. Despite a slow complexation rate with an association half-life of 31.4 h at pH 2 and room temperature, the [Zr(pypa)] complex is thermodynamically stable (log K ML = 38.92, pZr = 39.4). Radiochemical studies demonstrated quantitative radiolabeling achieved at 10 μM chelator concentration within 2 h at 40 °C and pH = 7, antibody-compatible conditions. Of the utmost importance, [ 89 Zr][Zr(pypa)] is highly kinetically inert upon challenge with excess EDTA and DFO ligands, superior to [ 89 Zr][Zr(DFO)] + , and maintains inertness toward human serum.

We show the synthesis of an in vivo stable mercury compound with functionality suitable for radiopharmaceuticals. The designed cyclic bisarylmercury was based on the water tolerance of organomercurials, higher bond dissociation energy of Hg-Ph to Hg-S, and the experimental evidence that acyclic structures suffer significant cleavage of one of the Hg-R bonds. The bispidine motif was chosen for its in vivo stability, chemical accessibility, and functionalization properties. Radionuclide production results in 197(m) HgCl 2 (aq), so the desired mercury compound was formed via a water-tolerant organotin transmetallation. The Hg-bispidine compound showed high chemical stability in tests with an excess of sulfur-containing competitors and high in vivo stability, without any observable protein interaction by human serum assay, and good organ clearance demonstrated by biodistribution and SPECT studies in rats. In particular, no retention in the kidneys was observed, typical of unstable mercury compounds. The nat Hg analogue allowed full characterization by NMR and HRMS., (© 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

[ 18 F]JNJ-64413739 has been evaluated as PET-ligand for in vivo quantification of purinergic receptor subtype 7 receptor (P2X7R) using Logan graphical analysis with a metabolite-corrected arterial plasma input function. In the context of a P2X7R PET dose occupancy study, we evaluated a minimally invasive approach by limiting arterial sampling to baseline conditions. Meanwhile, post dose distribution volumes (V T ) under blocking conditions were estimated by combining baseline blood to plasma ratios and metabolite fractions with an MR angiography driven image derived input function (IDIF). Regional postdose V T,IDIF values were compared with corresponding V T,AIF estimates using a arterial input function (AIF), in terms of absolute values, test-retest reliability and receptor occupancy. Compared to an invasive AIF approach, postdose V T,IDIF values and corresponding receptor occupancies showed only limited bias (Bland-Altman analysis: 0.06 ± 0.27 and 3.1% ± 6.4%) while demonstrating a high correlation (Spearman ρ = 0.78 and ρ = 0.98 respectively). In terms of test-retest reliability, regional intraclass correlation coefficients were 0.98 ± 0.02 for V T,IDIF compared to 0.97 ± 0.01 for V T,AIF. These results confirmed that a postdose IDIF, guided by MR angiography and using baseline blood and metabolite data, can be considered for accurate [ 18 F]JNJ-64413739 PET quantification in a repeated PET study design, thus avoiding multiple invasive arterial sampling and increasing dosing flexibility., (© 2021. The Author(s).)

P-Glycoprotein (P-gp) is an efflux pump located at the blood-brain barrier (BBB) that contributes to the protection of the central nervous system by transporting neurotoxic compounds out of the brain. A decline in P-gp function has been related to the pathogenesis of neurodegenerative diseases. P-gp inducers can increase the P-gp function and are considered as potential candidates for the treatment of such disorders. The P-gp inducer MC111 increased P-gp expression and function in SW480 human colon adenocarcinoma and colo-320 cells, respectively. Our study aims to evaluate the P-gp inducing effect of MC111 in the whole brain in vivo , using the P-gp tracer [ 18 F]MC225 and positron emission tomography (PET). Eighteen Wistar rats were treated with either vehicle solution, 4.5 mg/kg of MC111 (low-dose group), or 6 mg/kg of MC111 (high-dose group). Animals underwent a 60 min dynamic PET scan with arterial-blood sampling, 24 h after treatment with the inducer. Data were analyzed using the 1-tissue-compartment model and metabolite-corrected plasma as the input function. Model parameters such as the influx constant ( K 1 ) and volume of distribution ( V T ) were calculated, which reflect the in vivo P-gp function. P-gp and pregnane xenobiotic receptor (PXR) expression levels of the whole brain were assessed using western blot. The administration of MC111 decreased K 1 and V T of [ 18 F]MC225 in the whole brain and all of the selected brain regions. In the high-dose group, whole-brain K 1 was decreased by 34% ( K 1 -high-dose = 0.20 ± 0.02 vs K 1 -control = 0.30 ± 0.02; p < 0.001) and in the low-dose group by 7% ( K 1 -low-dose = 0.28 ± 0.02 vs K 1 -control = 0.30 ± 0.02; p = 0.42) compared to controls. Whole-brain V T was decreased by 25% in the high-dose group ( V T -high-dose = 5.92 ± 0.41 vs V T -control = 7.82 ± 0.38; p < 0.001) and by 6% in the low-dose group ( V T -low-dose = 7.35 ± 0.38 vs V T -control = 7.82 ± 0.37; p = 0.38) compared to controls. k 2 values did not vary after treatment. The treatment did not affect the metabolism of [ 18 F]MC225. Western blot studies using the whole-brain tissue did not detect changes in the P-gp expression, however, preliminary results using isolated brain capillaries found an increasing trend up to 37% in treated rats. The decrease in K 1 and V T values after treatment with the inducer indicates an increase in the P-gp functionality at the BBB of treated rats. Moreover, preliminary results using brain endothelial cells also sustained the increase in the P-gp expression. In conclusion, the results verify that MC111 induces P-gp expression and function at the BBB in rats. An increasing trend regarding the P-gp expression levels is found using western blot and an increased P-gp function is confirmed with [ 18 F]MC225 and PET.

For the first time, synthesis of bifunctional [2.2.2]-cryptands (CRYPT) and demonstration of radiolabeling with lead(II) (Pb 2+ ) isotopes are disclosed herein. The synthesis is convenient and high-yielding and gives access to three distinct bifunctional handles (azide (-N 3 ), isothiocyanate (-NCS), and tetrazine (-Tz)) that can enable the construction of radioimmunoconjugates for targeted and pretargeted therapy. Proof-of-principle CRYPT radiolabeling was successful with lead-203 ([ 203 Pb]Pb 2+ ) and demonstrated complexation efficiency superior to that of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and efficiency comparable to that of the current industry standard TCMC (1,4,7,10-tetraaza-1,4,7,10-tetra-(2-carbamoylmethyl)-cyclododecane). In vitro human serum stability assays demonstrated excellent [ 203 Pb]Pb-CRYPT stability over 72 h (91.7 ± 0.56%; n = 3). [ 203 Pb]Pb-CRYPT-radioimmunoconjugates were synthesized from the corresponding CRYPT-immunoconjugate or by conjugating [ 203 Pb]Pb-Tz-CRYPT to transcyclooctene modified trastuzumab (TCO-trastuzumab) via the inverse electron-demand Diels-Alder (IEEDA) reaction. This investigation reveals the potential for CRYPT ligands to become new industry standards for therapeutic and diagnostic radiometals in radiopharmaceutical elaboration.

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68 Ga-L1 and (4.7 ± 0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging., (© 2021 John Wiley & Sons A/S.)

Purpose: To precisely quantify split glomerular filtration rate by Tc-99m-DTPA renal dynamic imaging and plasma clearance in order to increase its consistency among doctors., Methods: Tc-99m-DTPA renal dynamic imaging was performed according to the conventional radionuclide renal dynamic imaging by five double-blinded doctors independently and automatically calculated split GFR, namely, gGFR. Moreover, the conventional radionuclide renal dynamic imaging was assessed to only outline the kidney, blank background, and automatically calculated split GFR, gGFR'. The total GFR value of patients, tGFR, was obtained by the double-plasma method. According to the formula, Precise GFR (pGFR) = gGFR'/(gGFR' + gGFR') × tGFR. The precise GFR value of the divided kidney, pGFR, was calculated. The Kendall's W test was used to compare the consistency of gGFR and pGFR drawn by five physicians., Results: According to Kendall's W consistency test, Kendall's coefficient of concordance was 0.834, p = 0.0001 using conventional method. The same five doctors used blank background again and the same standard Gates method to draw the kidneys, which automatically calculated gGFR'. Using input formula, the pGFR was calculated and Kendall's W consistency test (Kendall's coefficient of concordance = 0.956, p = 0.0001)., Conclusion: The combination of Tc-99m-DTPA renal dynamic imaging combined with the double-plasma method could achieve accurate split GFR, and because of the omission of influence factors, the consistency of pGFR obtained by different doctors using this method was significantly higher than that of conventional Tc-99m-DTPA renal dynamic imaging., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Xiaoxi Pang et al.)

Purpose: To evaluate total blood radioactivity (BR) after SIR-Spheres yttrium-90 ( 90 Y) radioembolization and differences in BR based on delivery method., Materials and Methods: Twenty participants with hepatic metastases undergoing first radioembolization were prospectively enrolled from December 2017 to June 2018. Blood samples were drawn at baseline and 0, 10, 20, 60, and 120 minutes after 90 Y administration. BR was measured with a γ-counter and scaled by estimated blood volume. Percentage of instilled radioactivity in the bloodstream was calculated as area under the fitted curve, and differences between delivery methods were examined with nonparametric statistical tests., Results: In 10 participants, resin microspheres were instilled with 50% Isovue 300 diluted in saline solution in the D line, and 10 others were treated with dextrose 5% in water (D5W) in the D line. Median administered activities were 944 MBq (range, 746-1,993 MBq) and 1,213 MBq (range, 519-2,066 MBq), respectively. Fraction of 90 Y in blood was significantly higher with dilute contrast agent than with D5W (median, 0.5% of injected activity vs 0.2%; P = .001). Among all participants, the maximum activity delivered was 2,066 MBq, and a maximum of 1% of administered radioactivity was measured as free 90 Y in blood. Assuming these highest-case values and complete decay of all free 90 Y in bone, a dose to red marrow of 132.3 mGy was calculated by Organ Level INternal Dose Assessment/EXponential Modeling., Conclusions: Blood sampling after radioembolization allowed for estimation of the time-activity curve and BR. Delivery with 50% contrast agent in saline solution resulted in a significant increase in BR vs D5W, even though the total BR for both groups was nominal., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Phosphonates-based agents are well-known bone-seeking radiopharmaceuticals with application in detection and therapy. With higher sensitivity and resolution offered by Positron Emission Tomography (PET), tracers based on this technique are gaining huge attention. 68 Ga-based generator and radiotracers render independence from the on-site cyclotron. We report the development of 68 Ga-labeled DOTA-based bismacrocyclic phosphonate derivative, for bone PET imaging. The synthesis and characterization of 68 Ga- DO3P-AME-DO3P was carried out in > 95% purity. The radiotracer displayed high stability and low binding affinity (<3%) to blood serum. High in vitro binding affinity were observed for synthetic hydroxyapatite, SAOS-2, osteoclast and osteoblast cells. In vivo pharmacokinetics revealed fast washout with biphasic release pattern. The deposition of radiotracer in osseous tissues was high (Bone/Muscle ratio:18), as studied from the biodistribution studies. In vivo PET/CT and biodistribution analyses revealed the ability of 68 Ga-DO3P-AME-DO3P to target and accumulate in bone, thus displaying its potential as a PET bone imaging agent., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Synthesis and characterisation of a dithiadiaza chelator NSNS2A, as well as copper complexes thereof are reported in this paper. Solution structures of copper(i/ii) complexes were calculated using density functional theory (DFT) and validated by both NMR and EPR spectroscopy. DFT calculations revealed a switch in the orientation of tetragonal distortion upon protonation, which might be responsible for poor stability of the Cu(II)NSNS2A complex in aqueous media, whilst the same switch in tetragonal distortion was experimentally observed by changing the solvent. The chelator was radiolabeled with 64Cu and evaluated using PET/MRI in rats. Despite a favorable redox potential to stabilize the cuprous state in vivo, the 64Cu(II)NSNS2A complex showed suboptimal stability compared to its tetraazamacrocyclic analogue, 64Cu(TE2A), with a significant 64Cu uptake in the liver.

Positron emission tomography (PET) uses radiotracers to quantify important biochemical parameters in human subjects. A radiotracer arterial input function (AIF) is often essential for converting brain PET data into robust output measures. For radiotracers labeled with carbon-11 (t 1/2  = 20.4 min), AIF is routinely determined with radio-HPLC of blood sampled frequently during the PET experiment. There has been no alternative to this logistically demanding method, neither for regular use nor validation. A 11 C-labeled tracer is always accompanied by a large excess of non-radioactive tracer known as carrier. In principle, AIF might be obtained by measuring the molar activity (A m ; ratio of radioactivity to total mass; Bq/mol) of a radiotracer dose and the time-course of carrier concentration in plasma after radiotracer injection. Here, we implement this principle in a new method for determining AIF, as shown by using [ 11 C]PBR28 as a representative tracer. The method uses liquid chromatography-tandem mass spectrometry for measuring radiotracer A m and then the carrier in plasma sampled regularly over the course of a PET experiment. A m and AIF were determined radiometrically for comparison. The new non-radiometric method is not constrained by the short half-life of carbon-11 and is an attractive alternative to conventional AIF measurement.

Purpose: [ 18 F]Fluoroethoxybenzovesamicol ([ 18 F]FEOBV) is a radioligand for the vesicular acetylcholine transporter (VAChT), a marker of the cholinergic system. We evaluated the quantification of [ 18 F]FEOBV in rats in control conditions and after partial saturation of VAChT using plasma and reference tissue input models and test-retest reliability., Procedure: Ninety-minute dynamic [ 18 F]FEOBV PET scans with arterial blood sampling were performed in control rats and rats pretreated with 10 μg/kg FEOBV. Kinetic analyses were performed using one- (1TCM) and two-tissue compartmental models (2TCM), Logan and Patlak graphical analyses with metabolite-corrected plasma input, reference tissue Patlak with cerebellum as reference tissue, standard uptake value (SUV) and SUV ratio (SUVR) using 60- or 90-min acquisition. To assess test-retest reliability, two dynamic [ 18 F]FEOBV scans were performed 1 week apart., Results: The 1TCM did not fit the data. Time-activity curves were more reliably estimated by the irreversible than the reversible 2TCM for 60 and 90 min as the influx rate K i showed a lower coefficient of variation (COV, 14-24 %) than the volume of distribution V T (16-108 %). Patlak graphical analysis showed a good fit to the data for both acquisition times with a COV (12-27 %) comparable to the irreversible 2TCM. For 60 min, Logan analysis performed comparably to both irreversible models (COV 14-32 %) but showed lower sensitivity to VAChT saturation. Partial saturation of VAChT did not affect model selection when using plasma input. However, poor correlations were found between irreversible 2TCM and SUV and SUVR in partially saturated VAChT states. Test-retest reliability and intraclass correlation for SUV were good., Conclusion: [ 18 F]FEOBV is best modeled using the irreversible 2TCM or Patlak graphical analysis. SUV should only be used if blood sampling is not possible.

[ 44/47 Sc]Sc 3+ , [ 68 Ga]Ga 3+ , and [ 111 In]In 3+ are the three most attractive trivalent smaller radiometalnuclides, offering a wide range of distinct properties (emission energies and types) in the toolbox of nuclear medicine. In this study, all three of the metal ions are successfully chelated using a new oxine-based hexadentate ligand, H 3 glyox, which forms thermodynamically stable neutral complexes with exceptionally high pM values [pIn (34) > pSc (26) > pGa (24.9)]. X-ray diffraction single crystal structures with stable isotopes revealed that the ligand is highly preorganized and has a perfect fit to size cavity to form [Sc(glyox)(H 2 O)] and [In(glyox)(H 2 O)] complexes. Quantitative radiolabeling with gallium-68 (RCY > 95%, [L] = 10 -5 M) and indium-111 (RCY > 99%, [L] = 10 -8 M) was achieved under ambient conditions (RT, pH 7, and 15 min) with very high apparent molar activities of 750 MBq/μmol and 650 MBq/nmol, respectively. Preliminary quantitative radiolabeling of [ 44 Sc]ScCl 3 (RCY > 99%, [L] = 10 -6 M) was fast at room temperature (pH 7 and 10 min). In vitro experiments revealed exceptional stability of both [ 68 Ga]Ga(glyox) and [ 111 In]In(glyox) complexes against human serum (transchelation <2%) and its suitability for biological applications. Additionally, on chelation with metal ions, H 3 glyox exhibits enhanced fluorescence, which was employed to determine the stability constants for Sc(glyox) in addition to the in-batch UV-vis spectrophotometric titrations; as a proof-of-concept these complexes were used to obtain fluorescence images of live HeLa cells using Sc(glyox) and Ga(glyox), confirming the viability of the cells. These initial investigations suggest H 3 glyox to be a valuable chelator for radiometal-based diagnosis (nuclear and optical imaging) and therapy.

We investigate biodistribution of gallium-labeled hydroxyethylidenediphosphonic acid ( 68 Ga-HEDP) and diethylenetriaminepentakis(methylenephosphonic acid) ( 68 Ga-DTPMP) in intact Wistar rats. It was shown that 68 Ga-DTPMP accumulated mainly in the bone tissue providing high femur/blood and femur/muscle ratios and had high stability in vivo. In contrast, 68 Ga-HEDP was characterized by low stability and high uptake of radioactivity in blood throughout the study. So 68 Ga-DTPMP can be considered as a new prospective radiotracer in oncology for imaging bone tissue metastasis by positron emission tomography.

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes enzymatic conversion of cortisone into the stress hormone cortisol. This first-in-human brain imaging study characterizes the kinetic modeling and test-retest reproducibility of [ 18 F]AS2471907, a novel PET radiotracer for 11β-HSD1. Eight individuals underwent one 180-min ( n  = 4) or two 240-min ( n  = 4) [ 18 F]AS2471907 PET brain scans (12 total) acquired on the high-resolution research tomograph (HRRT) scanner with arterial blood sampling. Imaging data were modeled with 1-tissue (1T) and 2-tissue (2T) compartment models and with multilinear analysis (MA1) to estimate [ 18 F]AS2471907 availability ( V T ). [ 18 F]AS2471907 demonstrated high, heterogeneous uptake throughout the brain. Of the compartment models, 2T best described [ 18 F]AS2471907 data. Estimates of V T were highly correlated between 2T and MA1 ( t*  = 30 min) with MA1 yielding V T values ranging from 3.2 ± 1.0 mL/cm 3 in the caudate to 15.7 ± 4.2 mL/cm 3 in the occipital cortex. The median absolute test-retest variability of 16 ± 5% and high intraclass correlation coefficient (ICC) values of 0.67-0.97 across regions indicate fair test-retest reliability but large intersubject variability. V T estimates using 180 min were within 10% of estimates using full acquisition time. In summary, [ 18 F]AS2471907 exhibits reasonable kinetic properties for imaging 11β-HSD1 in human brain.

Accurate assessment of the HER2 expression is an essential issue for predicting response to anti-HER2 therapy in breast cancer patients. The aim of this study was to evaluate 99m Tc-HYNIC-(Ser) 3 -LTVPWY ( 99m Tc-HYNIC-LY) peptide as a novel HER2-targeted radiolabeled peptide in healthy mice to examine the applicability of this imaging agent in a first-in-human clinical trial. To this end, pharmacokinetic and dosimetry studies were performed according to the ICH guideline M3 (R2) with 99m Tc-HYNIC-LY. To estimate the radiation-absorbed doses in humans, the accumulated activity in each mouse organ was calculated based on biodistribution data. In addition, toxicology assessment was performed based on mortality events, body weights, and serum biochemical, hematological, and histopathological assays. The pharmacokinetic study showed rapid blood clearance. Based on the results of biodistribution study, the highest radioactivity was observed in the kidneys. The projected absorbed doses to the kidneys, liver, lungs, stomach, and spleen were obtained as 1.70E-02, 1.42E-02, 1.02E-02, 8.62E-03, and 8.34E-03 mSv/MBq, respectively. The results also revealed that serum biochemical and hematological parameters were in the normal range. No significant morphologic alterations were observed in the liver, kidneys, and spleen tissues. Consequently, the results were indicative of the suitability of 99m Tc-HYNIC-LY peptide for advancement to a first-in-human clinical trial., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In some positron emission tomography (PET) studies, a reversibly binding radioligand is administered as a constant infusion to establish true equilibrium for quantification. This approach reduces scanning time and simplifies data analysis, but assumes similar behavior of the radioligand in plasma across the study population to establish true equilibrium in all subjects. Bias in outcome measurements can result if this assumption is not met. This work developed and validated a correction that reduces bias in total distribution volume ( V T ) estimates when true equilibrium is not present. This correction, termed tissue clearance correction (TCC), took the form V T = V T ( A ) / ( 1 + β γ V T ( A ) ) , where β is the radioligand clearance rate in tissue, γ is a radiotracer-specific constant, and V T(A) is the apparent V T . Simulations characterized the robustness of TCC across imperfect values of γ and β and demonstrated reduction to false positive rates. This approach was validated with human infusion data for three radiotracers: [ 18 F]FPEB, (-)-[ 18 F]flubatine, and [ 11 C]UCB-J. TCC reduced bias in V T estimates for all radiotracers and significantly reduced intersubject variance in V T for [ 18 F]FPEB data in some brain regions. Thus, TCC improves quantification of data acquired from PET infusion studies.

The interaction of dopaminergic and cholinergic neurotransmission in, e.g., Parkinson's disease has been well established. Here, D 2 receptor antagonists were used to assess changes in [ 18 F]-FEOBV binding to the vesicular acetylcholine transporter (VAChT) in rodents using positron emission tomography (PET). After pretreatment with either 10 mg/kg haloperidol, 1 mg/kg raclopride, or vehicle, 90 min dynamic PET scans were performed with arterial blood sampling. The net influx rate ( K i ) was obtained from Patlak graphical analysis, using a metabolite-corrected plasma input function and dynamic PET data. [ 18 F]-FEOBV concentration in whole-blood or plasma and the metabolite-corrected plasma input function were not significantly changed by the pretreatments (adjusted p > 0.07, Cohen's d 0.28-1.89) while the area-under-the-curve (AUC) of the parent fraction of [ 18 F]-FEOBV was significantly higher after haloperidol treatment (adjusted p = 0.022, Cohen's d = 2.51) than in controls. Compared to controls, the AUC of [ 18 F]-FEOBV, normalized for injected dose and body weight, was nonsignificantly increased in the striatum after haloperidol (adjusted p = 0.4, Cohen's d = 1.77) and raclopride (adjusted p = 0.052, Cohen's d = 1.49) treatment, respectively. No changes in the AUC of [ 18 F]-FEOBV were found in the cerebellum (Cohen's d 0.63-0.74). Raclopride treatment nonsignificantly increased K i in the striatum 1.3-fold compared to control rats (adjusted p = 0.1, Cohen's d = 1.1) while it reduced K i in the cerebellum by 28% (adjusted p = 0.0004, Cohen's d = 2.2) compared to control rats. Pretreatment with haloperidol led to a nonsignificant reduction in K i in the striatum (10%, adjusted p = 1, Cohen's d = 0.44) and a 40-50% lower K i than controls in all other brain regions (adjusted p < 0.0005, Cohen's d = 3.3-4.7). The changes in K i induced by the selective D 2 receptor antagonist raclopride can in part be quantified using [ 18 F]-FEOBV PET imaging. Haloperidol, a nonselective D 2 /σ receptor antagonist, either paradoxically decreased cholinergic activity or blocked off-target [ 18 F]-FEOBV binding to σ receptors. Hence, further studies evaluating the binding of [ 18 F]-FEOBV to σ receptors using selective σ receptor ligands are necessary.

Objectives: To study the pharmacokinetics, biodistribution, and injection doses of 99m Tc-TRODAT-1 in healthy adults., Methods: Thirty healthy individuals comprising 15 females and 15 males were randomly divided into three groups and the injection doses of 99m Tc-TRODAT-1 of group 1, 2, and 3 were 370 MBq, 740 MBq, and 1110 MBq, respectively. Assessments of subjective symptoms and tests were performed before and after injection. Blood and urine collections and whole-body planar imaging were analyzed at various time points. Bilateral brain striatal SPECT images obtained at 3.5 h PI were assessed visually and semiquantitatively., Results: No serious adverse events or deaths were observed in our study. The pharmacokinetic analysis showed that 99m Tc-TRODAT-1 was eliminated rapidly from the circulation, with just about 4% of the injected dose remaining in blood at 1 h post-injection. The mean cumulative urinary excretion over 24 h was just 2.96 ± 0.96%ID. The time-activity curve demonstrated that the radioactivity was mainly in liver and abdomen. The highest absorbed dose was in the dose-limiting organ, liver (20.88 ± 4.45 × 10 -3  mSv/MBq). The average effective dose was 5.22 ± 1.05 × 10 -3  mSv/MBq. The clarity of striatal images assessed visually in group 1 was worse than that in group 2 and 3. The semiquantitative analysis showed that there were no differences in striatum/cerebellum between the three groups (group 1: 1.77 ± 0.11, group 2: 1.62 ± 0.14, and group 3: 1.75 ± 0.20; P = 0.088)., Conclusions: 99m Tc-TRODAT-1 was safe to use in humans and showed the status of dopaminergic neurons specifically and clearly. The injection dose we suggested was 740 MBq.

The blood plasma radiometabolite analysis (RMA) is crucial procedure for quantitative analysis of positron emission tomography (PET) radioligands with no original reference region in the brain. Blood sampling and separating plasma for RMA has been a challenge especially with small animal PET research. This work aimed to overcome this problem by presenting a semi-automated lead shielded microextraction by packed sorbents (SLS-MEPS). The capability of SLS-MEPS was evaluated for RMA of [ 11 C]SMW139 as a PET radioligand in rat plasma samples. [ 11 C]SMW139 is a potential radioligand with high receptor binding for P2X 7 R in vivo. The validation method was individually performed for [ 11 C]SMW139 and [ 12 C]SMW139 with reversed phase high performance liquid chromatography (HPLC) utilizing radio- and UV-detector, respectively. The limits of detection (LOD) and quantification (LOQ) [ 11 C]SMW139 in rat plasma were 3 and 10 Becquerel (Bq), respectively. The standard calibration curve was obtained for [ 11 C]SMW139 within the concentration range 10-15000 Bq with over 0.995 coefficients for all assays. In addition, the capability of SLS-MEPS in combination with HPLC-UV for extraction of [ 12 C]SMW139 in rat plasma was also challenged and the obtained results showed a proper linearity (20-2000 μg mL -1 ), accuracy and repeatability., (Copyright © 2019. Published by Elsevier B.V.)

Objective: An arteriovenous graft (AVG) is indicated in hemodialysis patients with failed arteriovenous access. Early treatment of AVG infection is important because an advanced prosthetic infection leads to the removal of the prosthesis. The aim of this study was to evaluate the benefits of 18 F-FDG PET/CT and 99m Tc-HMPAO-WBC SPECT/CT in early detection of AVG infections., Subjects and Methods: Fifty-one AVGs were evaluated. 18 F-FDG PET/CT and 99m Tc-HMPAO-WBC SPECT/CT studies were performed at intervals of 10, 20-30, and 40-50 weeks after AVG insertion. Agreement between the imaging methods and reference parameters (i.e. clinical presentation, C-reactive protein and microbiological findings on the hemodialysis cannula extracted after hemodialysis from AVG) was evaluated., Results: The study results showed that focal accumulation of the radiopharmaceuticals can be considered a sign of AVG infection. At 10 weeks after AVG implantation, the focal 18 F-FDG findings showed the best agreement with the reference parameters (agreement coefficients AC1 - clinical status: 0.693, CRP: 0.605, cannula microbiology: 0.518, respectively). At 20 to 30 weeks after AVG implantation, the diagnostic value of focal 99m Tc-HMPAO-WBC accumulation increased (AC1 coefficients: 0.658, 0.658, 0.408) and was similar to that of focal 18 F-FDG uptake (AC1s: 0.656, 0.570, 0.409). Between 40 and 50 weeks since AVG implantation, the diagnostic significance of focal 99m Tc-HMPAO-WBC accumulation (AC1 coefficients: 0.771, 0.811, 0.611) slightly exceeded the diagnostic value of focal 18 F-FDG accumulation (AC1 coefficients: 0.524, 0.456, 0.569)., Conclusion: 18 F-FDG PET/CT and 99m Tc-HMPAO-WBC SPECT/CT can both serve as important tools contributing to early diagnosis of AVG infection.

Rare sugars are defined as monosaccharides that exist in nature but are only present in limited quantities. d-Allose is a rare sugar that has been reported to have some unique physiological effects. The present study describes suitable synthetic procedures for novel rare sugars of d-allose that are 18 F-labeled at the C-3 and C-6 positions and the preparation of the appropriate labeling precursors. The goal is to facilitate in vivo, noninvasive positron emission tomography (PET) investigation of the behavior of rare sugar analogs of d-allose in organs. We found five precursors that were practical for labeling, three for 3-deoxy-3-[ 18 F]fluoro-d-allose ([ 18 F]3FDA) and two for 6-deoxy-6-[ 18 F]fluoro-d-allose ([ 18 F]6FDA). With manual operation synthesis, the highest radiochemical conversion rates were 75% for [ 18 F]3FDA with a precursor of 1,2,4,6-tetra-O-acetyl-3-O-trifluoromethanesulfonyl-β-d-glucopyranose and 69% for [ 18 F]6FDA with a precursor of 1,2,3,4-tetra-O-acetyl-6-O-trifluoromethanesulfonyl-β-d-allopyranose. Furthermore, the practical yields of [ 18 F]3FDA and [ 18 F]6FDA using an automated synthesizer were also investigated. Radiochemical yields of 67% and 49% were obtained for [ 18 F]3FDA and [ 18 F]6FDA, respectively, in an automated synthesizer. As basic assessment of stability for use in PET scanning, high performance liquid chromatography analysis showed no decomposition of [ 18 F]3FDA and [ 18 F]6FDA after up to 6 h in rabbit blood plasma., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the correlation of computed tomography (CT) angiography and 99m Technetium-labeled red blood cell (RBC) scintigraphy to catheter angiography (CA) in the management of lower gastrointestinal bleeding (LGIB) while considering potential nephrotoxic effects of iodinated contrast., Materials and Methods: From November 2012 to August 2017, 223 CAs performed for LGIB, including massive, ongoing, and obscure bleeding, were retrospectively identified in patients with pre-procedural CT angiography or RBC scintigraphy. Positive correlations and sensitivities were calculated for CT angiography and RBC scintigraphy using CA results as reference. Correlations were then compared while considering certain clinical presentations of LGIB. Contrast dose was compared with maximum creatinine recorded 48-72 hours after., Results: Thirty-eight patients underwent CT angiography; 173 patients underwent RBC scintigraphy; and 12 patients completed both studies. CT angiography had a positive correlation of 67.7% (95% confidence interval [CI]: 57.0, 76.7) and sensitivity of 85.2% (95% CI: 66.3, 95.8), whereas RBC scintigraphy had a positive correlation of 29.3% (95% CI: 27.7, 31.0) and sensitivity of 94.4% (95% CI: 84.6, 98.8). CT angiography had higher positive correlation across all clinical presentations. No dose-toxicity relationship was observed between contrast and renal function (R 2 : 0.008), nor was there a difference in incidence of contrast-induced nephropathy between CT angiography and RBC scintigraphy (P = .30)., Conclusions: CT angiography has greater positive correlation to CA than RBC scintigraphy for assessing LGIB in active stable as well as hemodynamically unstable LGIB. As such, greater adoption of CT angiography may reduce the number of nontherapeutic CAs performed. Additional contrast associated with CT angiography does not result in increased nephrotoxicity., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Both 99m Tc-DTPA and 51 Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51 Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99m Tc-DTPA and 51 Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51 Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99m Tc-DTPA (CaNa 3 -DTPA) and 2.5 MBq 51 Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m 2 . No patients suffered from ascites or significant oedema. The mean 51 Cr-EDTA plasma clearance was 82 mL/min (range 16-226). The plasma clearances determined by the two methods were highly correlated ( r  = 0.993). The plasma clearance was significantly higher when measured by 99m Tc-DTPA than by 51 Cr-EDTA ( p  = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) -6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99m Tc-DTPA and that of 51 Cr-EDTA. Therefore, 99m Tc-DTPA can replace 51 Cr-EDTA when needed.

A new radio-HPLC detection system for measuring radioactivity in plasma samples during Positron Emission Tomography [PET] studies was developed. It is based on detecting both the positron and one of the annihilation photons. The system focused on improving the measurement of radioactivity concentrations on an unmetabolized positron emitting a radiopharmaceutical [PER] in the presence of its radioactive metabolites, all containing the same positron emitter. This paper presents a new detection configuration that improves the minimal detectible activity (MDA), simplify the measuring systems and reduces the error caused by the metabolites. The detector is based on a plastic scintillator and a BGO scintillation crystal, that produces different light output spectra for signal and noise events. By summing the positron and the annihilated photon light outputs, different spectra are obtained for the metabolite and for the parent compound tracer and for tracer marked by different positron emitting isotopes. This new detection system can improve quantitative analysis of plasma samples. The spectrum change provides up to a three-fold improvement in sensitivity compared to the currently used detection systems that measure only the annihilation coincidence events. Results showed that for 11 C the MDA was improved by approximately 520%. Furthermore, it provides the additional advantage of reliability by providing a method for separating the signal and noise readings from the gross detector readout. Accurate reconstruction algorithm of the signal was achieved over a wide measuring range even when the signal was only 5% of the gross measurement., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In the past decade, several developments have expanded the chemical toolbox for astatination and the preparation of 211 At-labeled radiopharmaceuticals. However, there is still a need for advanced methods for the synthesis of astatinated (bio)molecules to address challenges such as limited in vivo stability. Herein, we report the development of multifunctional 211 At-labeled reagents that can be prepared by applying a modular and versatile click approach for rapid assembly. The introduction of tetrazines as bioorthogonal tags enables rapid radiolabeling and radio-crosslinking, which is demonstrated by steric shielding of 211 At to significantly increase label stability in human blood plasma., Competing Interests: The authors declare no conflict of interest., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

[18F]T807 is a potent tau protein imaging agent. In order to fulfill the demand from preclinical and clinical studies, we developed an automated one-pot two-step synthesis of this potent tau imaging agent and studied its stability, and dosimetry in mice and monkeys. We also conducted a preliminary study of this imaging agent in humans. Using this one-pot two-step method, the radiochemical yield (RCY) of [18F]T807 was 20.5 ± 6.1% (n = 15) at the end of bombardment (EOB) in a synthesis time of 70±5 min. The chemical and radiochemical purities were >90% and the specific activities were 151 ± 52 GBq/μmol. The quality of [18F]T807 synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]T807 injection was stable at room temperature for up to 4 h after the end of synthesis (EOS). The estimated effective dose of the [18F]T807 injection extrapolated from monkeys was 19 μSv/MBq (n = 2), while the estimated effective doses of the [18F]T807 injection extrapolated from fasted and non-fasted mice were 123 ± 27 (n = 3) and 94 ± 19 (n = 4) μSv/MBq, respectively. This one-pot two-step automated method produced the [18F]T807 injection with high reproducibility and high quality. PET imaging and radiation dosimetry evaluation in mice and Formosan rock monkeys suggested that the [18F]T807 injection synthesized by this method is suitable for use in human PET imaging studies. Thus, this method could fulfill the demand for the [18F]T807 injection in both preclinical and clinical studies of tauopathies, especially for nearby study sites without cyclotrons., Competing Interests: The authors have declared that no competing interests exist.

In this study, we present the synthesis and characterization of the octadentate bispidine ligand, H 2 bispox 2 and its complexes with medicinally useful radiometal nuclides ( 111 In 3+ and 177 Lu 3+ ), including their X-ray diffraction single crystal structures with the stable isotopes. 111 InCl 3 radiolabels the ligand quantitatively at ambient conditions ([L] = 10 -5 M, room temperature, pH 7 and 15 min) and the in vitro human serum stability assays demonstrated high stability of the [ 111 In(bispox 2 )] + complex over 5 days. Moreover, the β - emitter 177 Lu radiolabels the ligand at 37 °C in 30 min (pH 8). These initial investigations reveal the potential of the octadentate bispidine ligand H 2 bispox 2 as a useful chelator for 111 In and 177 Lu-based radiopharmaceuticals.

Folate receptors (FR) are frequently overexpressed in a wide variety of human cancers. The aim of this study was to develop a trivalent 99m Tc(CO) 3 -labeled folate radiotracer containing isonitrile (CN-R) as the coordinating ligand for FR target imaging. [ 99m Tc]Tc-10 was HPLC purified (>98% chemical purity) and evaluated in vitro and in vivo as a potential agent for targeting FR-positive KB cells. [ 99m Tc]Tc-10 is a hydrophilic compound with partition coefficient of -2.90 ± 0.13 that showed high binding affinity (0.04 ± 0.002 nM) in vitro. High accumulation and retention of [ 99m Tc]Tc-10 (5.32 ± 2.99% ID/g) was observed in mice with KB tumors at 4 h after injection through the tail vein, which was significantly inhibited by co-injection of free folic acid (FA). SPECT (single photon emission tomography)/CT results were in accordance with biodistribution data at all time points., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Full quantification of dynamic positron emission tomography (PET) data requires the knowledge of tracer concentration in the arterial plasma. However, its accurate measurement is challenging due to the presence of radiolabeled metabolites and measurement noise. Mathematical models are fitted to the plasma data for both radiometabolite correction and data denoising. However, the models used are generally not physiologically informed and not consistently applied across studies even when quantifying the kinetics of the same radiotracer, introducing methodological variability affecting the results interpretation. The aim of this study was to develop and validate a unified framework for the arterial data modeling to achieve an accurate and fully automated description of the plasma tracer kinetics., Methods: The proposed pipeline employs basis pursuit techniques for estimating both radiometabolites and parent concentration models from the raw plasma measurements, allowing the resulting algorithm to be both robust and flexible to the different quality of data available. The pipeline was tested on four PET tracers ([ 11 C]PBR28, [ 11 C]MePPEP, [ 11 C]WAY-100635, and [ 11 C]PIB) with continuous and discrete blood sampling., Results: Compared to the standard procedure, the pipeline provided similar fit of the parent fraction but yielded a better description of the total plasma radioactivity, which in turn allowed a more accurate fit of the tissue PET data., Conclusion: The new method showed superior fits compared to the standard pipeline, for both continuous and discrete arterial sampling protocol, yielding to better description of PET data., Significance: The proposed pipeline has the potential to standardize the blood data modeling in dynamic PET studies given its robustness, flexibility and easiness of use.

P-Glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters at the blood-brain barrier (BBB), which effectively restrict brain distribution of diverse drugs, such as tyrosine kinase inhibitors. There is a crucial need for pharmacological ABCB1 and ABCG2 inhibition protocols for a more effective treatment of brain diseases. In the present study, seven marketed drugs (osimertinib, erlotinib, nilotinib, imatinib, lapatinib, pazopanib, and cyclosporine A) and one nonmarketed drug (tariquidar), with known in vitro ABCB1/ABCG2 inhibitory properties, were screened for their inhibitory potency at the BBB in vivo. Positron emission tomography (PET) using the model ABCB1/ABCG2 substrate [ 11 C]erlotinib was performed in mice. Tested inhibitors were administered as i.v. bolus injections at 30 min before the start of the PET scan, followed by a continuous i.v. infusion for the duration of the PET scan. Five of the tested drugs increased total distribution volume of [ 11 C]erlotinib in the brain ( V T,brain ) compared to vehicle-treated animals (tariquidar, + 69%; erlotinib, + 19% and +23% for the 21.5 mg/kg and the 43 mg/kg dose, respectively; imatinib, + 22%; lapatinib, + 25%; and cyclosporine A, + 49%). For all drugs, increases in [ 11 C]erlotinib brain distribution were lower than in Abcb1a/b (-/-) Abcg2 (-/-) mice (+149%), which suggested that only partial ABCB1/ABCG2 inhibition was reached at the mouse BBB. The plasma concentrations of the tested drugs at the time of the PET scan were higher than clinically achievable plasma concentrations. Some of the tested drugs led to significant increases in blood radioactivity concentrations measured at the end of the PET scan (erlotinib, + 103% and +113% for the 21.5 mg/kg and the 43 mg/kg dose, respectively; imatinib, + 125%; and cyclosporine A, + 101%), which was most likely caused by decreased hepatobiliary excretion of radioactivity. Taken together, our data suggest that some marketed tyrosine kinase inhibitors may be repurposed to inhibit ABCB1 and ABCG2 at the BBB. From a clinical perspective, moderate increases in brain delivery despite the administration of high i.v. doses as well as peripheral drug-drug interactions due to transporter inhibition in clearance organs question the translatability of this concept.

The development of functional imaging is a promising strategy for diagnosis and treatment of infectious and cancerous diseases. In this study, epirubicin was developed as a [ 99m Tc]-labeled radiopharmaceutical for the imaging of multi-drug-resistant Staphylococcus aureus infections. The labeling was carried out using sodium pertechnetate (Na 99m TcO 4 ; ~370 MBq). The other parameters such as amount of ligand, reducing agent (SnCl 2 .2H 2 O), and pH were optimized. The highest labeling yield ≥96.98% was achieved when 0.3 mg epirubicin, 13 μg SnCl 2 .2H 2 O, and ~370 MBq Na 99m TcO 4 were incubated at pH 7 for 15 min in the presence of ascorbic acid at room temperature. Radiochemical purity, stability, charge, and glomerular filtration rate were studied to evaluate the biological compatibility for in vivo administration. Biodistribution investigations showed radiotracer uptake (13.89 ± 1.56% ID/gm organ) by liver and 7.79 ± 0.38% ID/gm organ by kidneys at 30 min post-injection which promisingly wash out at 24 hr post-injection. Scintigraphy study showed selective uptake in S. aureus-infected tissues in contrast to turpentine oil-induced inflamed tissues. Target-to-non-target ratio (6.7 ± 0.05) was calculated at 1 hr post-injection using SPECT gamma camera. The results of this study reveal that the [ 99m Tc]-epirubicin can be a choice of imaging and monitoring the treatment process of multi-drug resistant S. aureus bacterial infections., (© 2018 John Wiley & Sons A/S.)

With the long-term goal of developing theranostic agents for applications in nuclear medicine, in this work we evaluated the well-known NOTA and NODAGA chelators as bifunctional chelators (BFCs) for the [ 99m Tc/ 186 Re]Tc/Re-tricarbonyl core. In particular, we report model complexes of the general formula fac-[M(L)(CO) 3 ] + (M = Re, 99m Tc, 186 Re) where L denotes NOTA-Pyr (1) or NODAGA-Pyr (2), which are derived from conjugation of NOTA/NODAGA with pyrrolidine (Pyr). Further, as proof-of-principle, we synthesized the peptide bioconjugate NODAGA-sst 2 -ANT (3) and explored its complexation with the fac-[Re(CO) 3 ] + and fac-[ 99m Tc][Tc(CO) 3 ] + cores; sst 2 -ANT denotes the somatostatin receptor (SSTR) antagonist 4-NO 2 -Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH 2 . Rhenium complexes Re-1 through Re-3 were synthesized and characterized spectroscopically, and receptor binding affinity was demonstrated for Re-3 in SSTR-expressing cells (AR42J, IC 50 = 91 nM). Radiolabeled complexes [ 99m Tc]Tc/[ 186 Re]Re-1/2 and [ 99m Tc]Tc-3 were prepared in high radiochemical yield (>90%, determined by radio-HPLC) by reacting [ 99m Tc]/[ 186 Re][Tc/Re(OH 2 ) 3 (CO) 3 ] + with 1-3 and correlated well with the respective Re-1 through Re-3 standards in comparative HPLC studies. All radiotracers remained intact through 24 h ( 99m Tc-labeled complexes) or 48 h ( 186 Re-labeled complexes) against 1 mM l-histidine and 1 mM l-cysteine (pH 7.4, 37 °C). Similarly, rat serum stability studies displayed no decomposition and low nonspecific binding of 9-24% through 4 h. Biodistribution of [ 99m Tc]Tc-3 in healthy CF-1 mice demonstrated a favorable pharmacokinetic profile. Rapid clearance was observed within 1 h post-injection, predominantly via the renal system (82% of the injected dose was excreted in urine by 1 h), with low kidney retention (% ID/g: 11 at 1 h, 5 at 4 h, and 1 at 24 h) and low nonspecific uptake in other organs/tissues. Our findings establish NOTA and NODAGA as outstanding BFCs for the fac-[M(CO) 3 ] + core in the design and development of organometallic radiopharmaceuticals. Future in vivo studies of [ 99m Tc]Tc- and [ 186 Re]Re-tricarbonyl complexes of NODAGA/NOTA-biomolecule conjugates will further probe the potential of these chelates for nuclear medicine applications in diagnostic imaging and targeted radiotherapy, respectively.

Heat-shock protein 90 (HSP90) is a molecular chaperone that activates oncogenic transformation in several solid tumors, including lung and breast cancers. Ganetespib, a most promising candidate among several HSP90 inhibitors under clinical trials, has entered Phase III clinical trials for cancer therapy. Despite numerous evidences validating HSP90 as a target of anticancer, there are few studies on PET agents targeting oncogenic HSP90. In this study, we synthesized and biologically evaluated a novel 18 F-labeled 5-resorcinolic triazolone derivative (1, [ 18 F]PTP-Ganetespib) based on ganetespib. [ 18 F]PTP-Ganetespib was labeled by click chemistry of Ganetespib-PEG-Alkyne (10) and [ 18 F]PEG-N 3 (11) with 37.3 ± 5.11% of radiochemical yield and 99.7 ± 0.09% of radiochemical purity. [ 18 F]PTP-Ganetespib showed proper LogP (0.96 ± 0.06) and good stability in human serum over 97% for 2 h. [ 18 F]PTP-Ganetespib showed high uptakes in breast cancer cells containing triple negative breast cancer (TNBC) MDA-MB-231 and Her2-negative MCF-7 cells, which are target breast cancer cell lines of HSP90 inhibitor, ganetespib, as an anticancer. Blocking of HSP90 by the pretreatment of ganetespib exhibited significantly decreased accumulation of [ 18 F]PTP-Ganetespib in MDA-MB-231 and MCF-7 cells, indicating the specific binding of [ 18 F]PTP-Ganetespib to MDA-MB-231 and MCF-7 cells with high HSP90 expression. In the biodistribution and microPET imaging studies, the initial uptake into tumor was weaker than in other thoracic and abdominal organs, but [ 18 F]PTP-Ganetespib was retained relatively longer in the tumor than other organs. The uptake of [ 18 F]PTP-Ganetespib in tumors was not sufficient for further development as a tumor-specific PET imaging agent by itself, but this preliminary PET imaging study of [ 18 F]PTP-Ganetespib can be basis for developing new PET imaging agents based on HSP90 inhibitor, ganetespib., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Overexpression of Cyclooxygenase-2 (COX-2) enzyme is associated with the pathogenesis of inflammation, cancers, stroke, arthritis, and neurological disorders. Because of the involvement of COX-2 in these diseases, quantification of COX-2 expression using Positron Emission Tomography (PET) may be a biological marker for early diagnosis, monitoring of disease progression, and an indicator of effective treatment. At present there is no target-specific or validated PET tracer available for in vivo quantification of COX-2. The objective of this study is to evaluate [ 11 C]TMI, a selective COX-2 inhibitor (Ki ≤ 1 nM) in nonhuman primates using PET imaging. PET imaging in baboons showed that [ 11 C]TMI penetrates the blood brain barrier (BBB) and accumulates in brain in a somewhat heterogeneous pattern. Metabolite analyses indicated that [ 11 C]TMI undergoes no significant metabolism of parent tracer in the plasma for baseline scans, however a relative faster metabolism was found for blocking scan. All the tested quantification approaches provide comparable tracer total distribution volume (V T ) estimates in the range of 3.2-7 (mL/cm 3 ). We observed about 25% lower V T values in blocking studies with meloxicam, a nonselective COX-2 inhibitor, compared to baseline [ 11 C]TMI binding. Our findings indicate that [ 11 C]TMI may be a suitable PET tracer for the quantification of COX-2 in vivo. Further experiments are needed to confirm the potential of this tracer in COX-2 overexpressing models for brain diseases., (Copyright © 2018. Published by Elsevier Ltd.)

Cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy is a promising biomarker for dementia with Lewy bodies (DLB). However, we experienced a patient with cognitive decline, parkinsonism, and a decreased MIBG uptake who turned out to have HIV dementia. Normal dopamine transporter single-photon emission computed tomography reduced the possibility of comorbid Lewy body pathology causing the patient' s parkinsonism. The decreased MIBG uptake was most likely due to postganglionic sympathetic nerve denervation, which can also be caused by HIV. This case further emphasizes the importance of excluding other causes of autonomic neuropathy, including HIV infection, before interpreting MIBG scans.

HYNIC-3PRGD 2 is used to prepare a new 99m Tc-radiolabeled tracer. HYNIC-3PRGD 2 , which has a high binding affinity for the integrin α v β 3 due to its special structure, has become a promising tumor imaging agent for diagnosis and monitor of the clinical response to therapeutic effects of anti-tumor agents. Here, we developed and validated a method for determination of HYNIC-3PRGD 2 concentration in rat plasma using ultra-high performance liquid chromatography-tandem mass spectrometry system. Following sample extraction by methanol precipitation, satisfactory separation through chromatography was achieved on an hydrophilic reverse-phase C 18 column AQ (2.1 mm × 100 mm, 2.7 μm) at a flow rate of 0.2 mL·min -1 with an gradient elution using mobile phase consisting of ultrapure water and acetonitrile fortified with 0.1% formic acid respectively. The calibration curve was developed over a linear range of 3.125-100 ng·mL -1 with the lower limit of quantification of 3.125 ng·mL -1 . The HYNIC-3PRGD 2 and its internal standard c(RGDfK)(RK5) were detected and quantified with the multiple reaction monitoring (MRM) mode on a triple-quadrupole tandem mass spectrometer. This method was successfully validated and applied for pharmacokinetic evaluation of HYNIC-3PRGD 2 during pre-clinical experiments., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Challenges facing cardiovascular imaging necessitate innovation of better radiopharmaceuticals to augment or replace the existing ones. This research assesses the ability and competency of radioiodinated esmolol as a potential cardio selective imaging agent. Radioiodinated esmolol was synthesized with 97.3 ± 0.3% radiochemical yield and with high stability up to 48 h at room temperature as well as in rat serum. Molecular modeling study was performed to confirm the binding of iodinated esmolol to β 1 -adrenergic receptor. Its biodistribution studies in normal Swiss albino mice showed high heart uptake (38.5 ± 0.11%ID/g at 5 min p.i.), heart/liver ratio nearly 3.85:1 and heart/lungs ratio was about 7:1 at 5 min p.i. The evidenced selectivity of the radioiodinated esmolol to β 1 -adrenoceptor was confirmed by prior injection of cold esmolol. Gamma camera biodistribution pattern showed that radioiodinated esmolol accumulated selectively in heart., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To investigate DNA double-strand breaks (DSBs) in blood lymphocytes induced by two-day 99m Tc-MIBI myocardial perfusion scintigraphy (MPS) using y-H2AX immunofluorescence microscopy and to correlate the results with 99m Tc activity in blood samples., Methods: Eleven patients who underwent two-day MPS were included. DSB blood sampling was performed before and 5min, 1h and 24h after the first and second radiotracer injections. 99m Tc activity was measured in each blood sample. For immunofluorescence microscopy, distinct foci representing DSBs were quantified in lymphocytes after staining for the phosphorylated histone variant y-H2AX., Results: The 99m Tc-MIBI activity measured on days one and two was similar (254±25 and 258±27 MBq; p=0.594). Compared with baseline DSB foci (0.09±0.05/cell), a significant increase was found at 5min (0.19±0.04/cell) and 1h (0.18±0.04/cell) after the first injection and at 5min and 1h after the second injection (0.21±0.03 and 0.19±0.04/cell, respectively; p=0.003 for both). At 24h after the first and second injections, the number of DSB foci had returned to baseline (0.06±0.02 and 0.12±0.05/cell, respectively). 99m Tc activity levels in peripheral blood samples correlated well with DSB counts (r=0.451)., Conclusions: DSB counts reflect 99m Tc-MIBI activity after injection for two-day MPS, and might allow individual monitoring of biological effects of cardiac nuclear imaging., Key Points: • Myocardial perfusion scintigraphy using 99m Tc induces time-dependent double-strand breaks (DSBs) • γ-H2AX immunofluorescence microscopy shows DSB as an early response to radiotracer injection • Activity measurements of 99m Tc correlate well with detected DSB • DSB foci induced by 99m Tc return to baseline 24h after radiotracer injection.

Rationale: Hyperthermic isolated lung Perfusion (ILuP) is used to deliver high-dose chemotherapy to pulmonary metastases while sparing systemic toxicity. Accurate leakage monitoring is however necessary. This study aimed to verify the accuracy of radionuclide leakage monitoring in patients undergoing ILuP, by comparing this method with serial blood sampling., Methods: A total of 15 consecutive ILuP procedures were performed on eleven patients affected by lung metastases from soft tissue sarcoma. After establishing isolated perfusion, erythrocytes of systemic blood (SB) were labelled with 0.2 MBq/kg of 99m Tc. The baseline SB counting rate (CR) was assessed using a γ-probe. Subsequently, erythrocytes of the circuit blood (CB) were labelled with 2 Mbq/kg of 99m Tc. Radioactivity leakage factor (RLF) was continuously measured using a formula, accounting for CR, systemic/circuit activity ratio and total/systemic volume ratio. The TNF-α concentration in SB and CB was measured by enzymelinked immunosorbent assay (ELISA) throughout the procedure., Results: RLF averaged 2.3 ± 1.5%, while the systemic/circuit TNF-α ratio was 0.05 ± 0.12%. These two indices were strictly correlated in all of the procedures (average Rvalue 0.88 ± 0.07). RLF exceeded 5% during three of 15 procedures, prompting the application of compensatory manoeuvres. ELISA confirmed a marked increase in systemic TNF-α levels in these patients (2.6 ± 3.5 ng/ml). Conversely, patients whose RLF did not exceed the 5% threshold presented a mean TNF-α of 0.02 ± 0.005 ng/ml (p < 0.01)., Conclusions: In patients submitted to ILuP, RLF monitoring is feasible and accurate. Moreover, it grants immediate results, permitting for the adoption of corrective manoeuvres for leakage, thus minimising toxicity.

To investigate the influence of background blood metabolism on liver uptake of 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) and search for an appropriate corrective method.Positron emission tomography/computed tomography (PET/CT) and common serological biochemical tests of 633 healthy people were collected retrospectively. The mean standardized uptake value (SUV) of the liver, liver artery, and portal vein (i.e., SUVL, SUVA, and SUVP) were measured. SUVL/A was calculated as SUVL/SUVA, while SUVL/P was calculated as SUVL/SUVP. SUV of liver parenchyma (SUVLP) was calculated as SUVL - .3 × (.75 × SUVP + .25 × SUVA). The coefficients of variation (CV) of SUVL, SUVL/A, SUVL/P, and SUVLP were compared to assess their interindividual variations. Univariate and multivariate analyses were performed to identify vulnerabilities of these SUV indexes to common factors assessed using serological liver functional tests.SUVLP was significantly larger than SUVL (2.19 ± .497 vs 1.88 ± .495, P < .001), while SUVL/P was significantly smaller than SUVL (1.72 ± .454 vs 1.88 ± .495, P < .001). The difference between SUVL/A and SUVL was not significant (1.83 ± .500 vs 1.88 ± .495, P = .130). The CV of SUVLP (22.7%) was significantly smaller than that of SUVL (22.7%:26.3%, P < .001), while the CVs of SUVL/A (27.2%) and SUVL/P (26.4%) were not different from that of SUVL (P = .429 and .929, respectively). Fewer variables independently influenced SUVLP than influenced SUVL, SUVL/A, and SUVL/P; Only aspartate aminotransferase, body mass index, and total cholesterol, all P-values <.05.The activity of background blood influences the variation of liver SUV. SUVLP might be an alternative corrective method to reduce this influence, as its interindividual variation and vulnerability to effects from common factors of serological liver functional tests are relatively lower than the commonly used SUVL.

Aim: To investigate the influence of scan time point and volume of intravenous contrast material in 18F-FDG PET/CT on maximum and mean standardized uptake values (SUV max / mean ) in bloodpool and liver., Methods: In 120 patients scheduled for routine whole-body 18F-FDG PET/CT the maximum and mean standardized uptake values (SUV max /SUV mean ) in the liver and blood pool were measured after varying scan time-point (delay 0 s-140 s post injectionem) and volume of contrast material (CM; 0 ml, 80 ml, 100 ml of 300 mg/ml of Iodine). Six groups of 20 patients were investigated: (1) without intravenous CM, (2-5) injection of 100 ml CM with a delay of 80 s (2), 100 s (3), 120 s (4), 140 s (5), and 80 ml CM and a delay of 100 s (6). SUV max , SUV mean , maximum Hounsfield units (HU max ) and average Hounsfield units (HU av ) were calculated with the use of manually drawn regions of interests (ROIs) over the aortic arch and healthy liver tissue., Results: SUV max in bloodpool was significantly higher in group 3, 4 and 6 compared to group 1. Groups 2 and 5 also showed higher mean values of SUV max , but the difference was not significant. SUV mean in bloodpool was also higher in groups 2, 3, 4, 5 and 6 compared to group 1, but the differences were only statistically significant in group 3. Both SUV max and SUV mean in healthy liver tissue did not show significant differences when compared to the non contrast-enhanced control group., Conclusion: SUV max and to a lesser extent SUV mean measured in CM enhanced FDG PET/CT in blood pool could be significantly altered in high contrast CT examinations. This should be kept in mind in PET/CT protocols and evaluation relying on SUV max and SUV mean , for example when used in the assessment of therapy response, especially in highly vascularized tumor lesions. ZIEL:: Das Ziel dieser Studie war den Einfluss von unterschiedlichen Messzeitpunkten und Volumina bei der Gabe von intravenösem Kontrastmittel in der 18F-FDG PET/CT auf SUV max und SUV mean im Blutpool und Lebergewebe zu untersuchen., Methoden: In 120 Patienten, geplant für eine Ganzkörper 18F-FDG -PET/CT, wurden die maximalen und durchschnittlichen standardisierten Aufnahmewerte (SUV max /SUV mean ) in der Leber und im Blutpool, jeweils nach unterschiedlichen Messzeitpunkten (Verzögerung 0 s-140 s post injectionem) und verschiedenen Volumina von Kontrastmittel (KM; 0 ml, 80 ml, 100 ml mit einer Konzentration von 300 mg/ml Jod) gemessen. Sechs Gruppen von je 20 Patienten wurden untersucht: (1) ohne intravenöses KM, (2-5) Injektion von 100 ml KM mit einer Verzögerung von 80 s (2), 100 s (3), 120 s (4), 140 s (5), und 80 ml KM mit einer Verzögerung von 100 s (6). Es wurden jeweils die SUV max , SUV mean , die maximalen and die durchschnittlichen Hounsfield Einheiten (HU av , HU max ) anhand manuell gezeichneter Bereiche von Interesse (ROIs) im Aortenbogen und im gesunden Lebergewebe berechnet., Ergebnisse: Die SUV max im Blutpool waren im Vergleich zur Gruppe 1 signifikant höher in Gruppe 3, 4 und 6. Die Gruppen 2 und 5 zeigten ebenfalls höhere Durchschnittswerte von SUV max , der Unterschied war jedoch nicht signifikant. Die SUV mean im Blutpool waren im Vergleich zur Gruppe 1 ebenfalls höher in den Gruppen 2, 3, 4, 5 und 6, allerdings waren die Unterschiede nur in Gruppe 3 statistisch signifikant. Im Lebergewebe zeigten sowohl SUV max , als auch SUV mean keine signifikanten Unterschiede im Vergleich zu der nativen Kontrollgruppe., Schlussfolgerungen: In der Kontrastmittel-gestützten FDG PET/CT können die SUV max und in geringerem Ausmaß auch SUV mean im Blutpool durch Hochkontrast-CT Untersuchungen signifikant beeinflusst werden. Dies sollte bei PET/CT Protokollen bzw. Auswertungen, die auf SUV max und SUV mean beruhen, berücksichtigt werden, zum Beispiel bei der Beurteilung des Therapieansprechens insbesondere bei stark vaskularisiertem Tumorgewebe., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Schattauer GmbH.)

Background: Candida spp is an etiologic agent of fungal infections in hospitals and resistance to treatment with antifungals has been extensively reported. Thus, it is very important to develop formulations that increase effectiveness with low toxicity. In this sense, nanocarriers have been investigated, once they modify drug biodistribution profile. Thus, this study aimed to evaluate the biodistribution of free and encapsulated 99m Tc-fluconazole into nanocapsules (NCs) in an experimental immunosuppressed murine model of Candida albicans infection., Methods: Fluconazole was radiolabeled with technetium-99 metastable ( 99m Tc) and encapsulated into conventional ( 99m Tc-Fluconazole-PLA-POLOX) and surface-modified ( 99m Tc-Fluconazole-PLA-PEG) NCs by the interfacial deposition of the preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by solvent evaporation. The size distribution and zeta potential of the NCs preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. Free and encapsulated 99m Tc-fluconazole were administered intravenously in immunosuppressed mice bearing a local infection induced by Candida Albicans inoculation in the right thigh muscle. At pre-established time intervals, tissues and organs of interest were removed and radioactivity was measured in an automatic gamma radiation counter., Results: The NCs diameter was between 200 and 400 nm with negative zeta potential values. Free 99m Tc-fluconazole was more rapidly eliminated by the renal system compared to the encapsulated drug in NCs, which remained longer in blood circulation. The uptake of conventional NCs by mononuclear phagocyte system organs was higher than the one demonstrated by the surface-modified NCs. Both NCs remained longer in the infectious focus when compared to free 99m Tc-fluconazole, but the results did not show a significant difference between NC formulations., Conclusion: These data indicate that these NCs might represent a therapeutic alternative for the treatment of candidiasis, once they remain more time in the infectious focus, allowing high retention of 99m Tc-fluconazole at this site., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Due to high expression of CXCR4 (CXC chemokine receptor type 4) receptors in many tumors and metastasis, synthesis and labeling of CXCR4 receptor-targeted analogs as tumor imaging agents have been encouraged. Herein, CXCR4 receptor-targeted peptide antagonist was prepared and thereafter its labeling with 99m Tc by a bifunctional chelating agent and tricine coligand was developed. Radiotracer purity, stability, and tumor cell binding were assessed. Bioevaluation of radiotracer was performed in mice bearing xenograft tumor. More than 95% labeling yield and stability up to 24 hours were observed. Radiotracer-related tumor accumulation was 3.61 ± 0.15% ID/g at 1 hour postinjection. High stability and specific tumor uptake are important characteristics of the radiotracer that could nominate this as a targeted imaging agent in the future.

Arachidonic acid (AA) is involved in signal transduction, neuroinflammation, and production of eicosanoid metabolites. The AA brain incorporation coefficient (K*) is quantifiable in vivo using [ 11 C]AA positron emission tomography, although repeatability remains undetermined. We evaluated K* estimates obtained with population-based metabolite correction (PBMC) and image-derived input function (IDIF) in comparison to arterial blood-based estimates, and compared repeatability. Eleven healthy volunteers underwent a [ 11 C]AA scan; five repeated the scan 6 weeks later, simulating a pre- and post-treatment study design. For all scans, arterial blood was sampled to measure [ 11 C]AA plasma radioactivity. Plasma [ 11 C]AA parent fraction was measured in 5 scans. K* was quantified using both blood data and IDIF, corrected for [ 11 C]AA parent fraction using both PBMC (from published values) and individually measured values (when available). K* repeatability was calculated in the test-retest subset. K* estimates based on blood and individual metabolites were highly correlated with estimates using PBMC with arterial input function (r = 0.943) or IDIF (r = 0.918) in the subset with measured metabolites. In the total dataset, using PBMC, IDIF-based estimates were moderately correlated with arterial input function-based estimates (r = 0.712). PBMC and IDIF-based K* estimates were ∼6.4% to ∼11.9% higher, on average, than blood-based estimates. Average K* test-retest absolute percent difference values obtained using blood data or IDIF, assuming PBMC for both, were between 6.7% and 13.9%, comparable to other radiotracers. Our results support the possibility of simplified [ 11 C]AA data acquisition through eliminating arterial blood sampling and metabolite analysis, while retaining comparable repeatability and validity., (© 2017 Wiley Periodicals, Inc.)

Cancer is found to be the leading cause of death worldwide characterized by uncontrolled cell division. Nuclear medicines imaging using radiopharmaceuticals have pronounced potential for the diagnosis and treatment of cancers. Cyclophosphamide (CPH) is an antineoplastic drug which targets selectively cancer cells. In the present work, labeling of CPH with Tc-99m is performed for diagnostic purpose, which gave labeling yield as high as 99% using 20 μg SnCl 2 ·2H 2 O, 200 μg of ligand at pH 7 for 10 min reaction time at room temperature. The characterization of the prepared complex was performed using ITLC, electrophoresis, and HPLC. In vitro stability was analyzed in the presence of human serum at 37°C which has maximum value of 94 ± 0.5. The biodistribution studies of 99m Tc-CPH were performed in normal and tumor bearing Swiss Webster mice. The high accumulation of 99m Tc-CPH was observed in liver and tumours respectively at 4 hr after injection. Biodistribution results revealed that 99m Tc-CPH may be a potential tumour diagnostic agent simultaneously with chemotherapy., (© 2017 John Wiley & Sons A/S.)

Cytosolic phospholipase A2α (cPLA2α) may play a critical role in neuropsychiatric and neurodegenerative disorders associated with oxidative stress and neuroinflammation. An effective PET radioligand for imaging cPLA2α in living brain might prove useful for biomedical research, especially on neuroinflammation. We selected four high-affinity (IC 50 2.1-12 nm) indole-5-carboxylic acid-based inhibitors of cPLA2α, namely 3-isobutyryl-1-(2-oxo-3-(4-phenoxyphenoxy)propyl)-1H-indole-5-carboxylic acid (1); 3-acetyl-1-(2-oxo-3-(4-(4-(trifluoromethyl)phenoxy)phenoxy)propyl)-1H-indole-5-carboxylic acid (2); 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-(2-oxo-3-(4-phenoxyphenoxy)propyl)-1H-indole-5-carboxylic acid (3); and 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-(3-(4-octylphenoxy)-2-oxopropyl)-1H-indole-5-carboxylic acid (4), for labelling in carboxyl position with carbon-11 (t 1/2 =20.4 min) to provide candidate PET radioligands for imaging brain cPLA2α. Compounds [ 11 C]1-4 were obtained for intravenous injection in adequate overall yields (1.1-5.5 %) from cyclotron-produced [ 11 C]carbon dioxide and with moderate molar activities (70-141 GBq μmol -1 ) through the use of Pd 0 -mediated [ 11 C]carbon monoxide insertion on iodo precursors. Measured logD 7.4 values were within a narrow moderate range (1.9-2.4). After intravenous injection of [ 11 C]1-4 in mice, radioactivity uptakes in brain peaked at low values (≤0.8 SUV) and decreased by about 90 % over 15 min. Pretreatments of the mice with high doses of the corresponding non-radioactive ligands did not alter brain time-activity curves. Brain uptakes of radioactivity after administration of [ 11 C]1 to wild-type and P-gp/BCRP dual knock-out mice were similar (peak 0.4 vs. 0.5 SUV), indicating that [ 11 C]1 and others in this structural class, are not substrates for efflux transporters., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Heart imaging radiopharmaceuticals could improve the diagnostic value of routine heart scanning for detecting cardiac disorders. The aim of the study was to prepare high radiochemical purity 99mTc-Digoxin in a yield of about 98%. The optimal conditions for labelling were as follows: 100μg of Digoxin, 2μg of SnCl2•2H2O, room temperature (25±1°C), reaction retention time of 30 min at pH 7. Under these conditions, the radiochemical yield of 99m Tc-Digoxin reaches 98%. In vivo bio distribution was performed in normal Swiss Albino mice at different time intervals after administration of 99m Tc-Digoxin.Scintigraphic study of 99m Tc-Digoxin was performed in rabbits. The heart uptake of 99m Tc-Digoxin was sufficiently high and thus may be a potential myocardial imaging radiopharmaceutical applicable in cardiology.

Background: Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB., Objective: This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling., Methods: Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT., Results: Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one., Conclusion: Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)