Fully automatic input function determination program for simple noninvasive 123I-IMP microsphere cerebral blood flow quantification method

We recently developed a simple noninvasive ¹²³I-IMP microsphere (SIMS) method using chest dynamic planar images and brain single photon emission computed tomography. The SIMS method is an automatic analysis method, except for the process of setting the region of interest (ROI) of the input function. If a fully automatic ROI setting algorithm can be developed to determine the input function for the SIMS method, repeatability and reproducibility of the analysis of regional cerebral blood flow (rCBF) of the SIMS method can be guaranteed. The purpose of this study is to develop a fully automatic input function determination program for the SIMS method and to confirm the clinical usefulness of this program.The automatic input function determination program consists of two ROI setting programs for the PA and lung regions, and it is developed using the image phase analysis of a chest RI angiogram. To confirm the clinical usefulness of this program, the rCBF in 34 patients measured using the automatic method were compared with the values obtained through the manual setting method.Input functions by the automatic and manual methods were approximately equal. A good correlation was observed between the rCBF values obtained by the automatic method and those obtained by the manual setting method (r = 0.96, p < 0.01).Further, the total time taken for the automatic SIMS analysis is 1–2 min as compared to 20–30 min for the current analysis, and therefore, this technique contributes to the improvement of the throughput of nuclear medical examinations.     

Comparaison de quatre méthodes d’évaluation des modifications de la perfusion cérébrale en tomoscintigraphie

IntroductionWe compared four different methods to assess changes in cerebral blood flow in patients with normal pressure hydrocephalus using cerebral ECD SPECT before and after injection of acetazolamide.Material and methodsEleven patients underwent cerebral SPECT before and after injection of 1 g of acetazolamide using a ^99mTc-ECD split-dose protocole with a first injection of 370 MBq and a second of 1100 MBq. After reconstruction of volumes with Neurogam^® (Segami) software, we compared visual analysis to semi quantitative analysis provided by Neurogam software, ratios methods and parametric analysis under SPM99 and SPM2.ResultsVisual analysis is immediate but frequently misleading. The contribution of Neurogam depends on the reader's skill and may be significant for non expert readers. The manual semi-automatic method is tedious and its results depend on the choice of the areas of interest and reference necessary for activity normalization. At last, the automatic method carried out by SPM is reliable for population analysis, but its efficiency for individual analysis remains to be evaluated.     

Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

Background

Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with ^99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation.

Methods

Ten adult sleepwalkers and twelve controls with normal sleep were scanned using ^99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers.

Results

During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls.

Conclusions

Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness.     

Intérêt d’une semi-quantification et d’une analyse statistique automatique pour l’interprétation de la tomoscintigraphie cérébrale de perfusion dans la maladie d’Alzheimer

IntroductionAs the visual interpretation of the brain perfusion SPECT for the diagnosis of Alzheimer's disease might be difficult, it is wished to benefit from techniques allowing to improve the diagnostic accuracy especially for the inexperienced readers.Materials and methodsThree readers retrospectively interpreted 77 ^99mTc-ECD SPECT studies within the context of suspected neurodegenerative disease. The probability of Alzheimer's disease was quoted from 1 to 5, and the optimum sensitivity and specificity values were determined from ROC curves. The readers also attributed a hypoperfusion score to 13 brain regions; a diagnosis was obtained from this semi-quantification using a simple logic rule. The SPECT scans were also analyzed using the Planet Neuro software and a diagnosis was reached from a threshold for 2 of the 90 analyzed regions. The gold standard was established by a comprehensive neurological evaluation with at least 5 years of follow-up.ResultsThe sensitivities and specificities of the three readers were 50 %, 56 %, 28 % and 76 %, 83 % and 90 %, respectively. Using the semi-quantification they were 50 %, 67 %, 61 % and 54 %, 85 %, 69 %. The results of two readers were more in agreement. Using the automatic quantification, sensitivity was 78 % and specificity 81 %.ConclusionThe semi-quantification seems to ameliorate the results of and the agreement between certain readers. However, the automatic quantification seems to be the only way of assisting all of the readers to improve their diagnostic performances.     

Comparison of 90Y SIRT predicted and delivered absorbed doses using a PSF conversion method

PurposeThe aims of this study were to develop and apply a method to correct for the differences in partial volume effects of pre-therapy Technetium-99 m (^99mTc)-MAA SPECT and post-therapy Yttrium-90 (⁹⁰Y) bremsstrahlung SPECT imaging in selective internal radiation therapy, and to use this method to improve quantitative comparison of predicted and delivered ⁹⁰Y absorbed doses.MethodsThe spatial resolution of ^99mTc SPECT data was converted to that of ⁹⁰Y SPECT data using a function calculated from ^99mTc and ⁹⁰Y point spread functions. This resolution conversion method (RCM) was first applied to ^99mTc and ⁹⁰Y SPECT phantom data to validate the method, and then to clinical data to assess the power of ^99mTc SPECT imaging to predict the therapeutic absorbed dose.ResultsThe maximum difference between absorbed doses to phantom spheres was 178%. This was reduced to 27% after the RCM was applied.The clinical data demonstrated differences within 38% for mean absorbed doses delivered to the normal liver, which were reduced to 20% after application of the RCM. Analysis of clinical data showed that therapeutic absorbed doses delivered to tumours greater than 100 cm³ were predicted to within 52%, although there were differences of up to 210% for smaller tumours, even after the RCM was applied.ConclusionsThe RCM was successfully verified using phantom data. Analysis of the clinical data established that the ^99mTc pre-therapy imaging was predictive of the ⁹⁰Y absorbed dose to the normal liver to within 20%, but had poor predictability for tumours smaller than 100 cm³.     

3D image-based dosimetry for Yttrium-90 radioembolization of hepatocellular carcinoma: Impact of imaging method on absorbed dose estimates

BackgroundTo improve therapy outcome of Yttrium-90 selective internal radiation therapy (⁹⁰Y SIRT), patient-specific post-therapeutic dosimetry is required. For this purpose, various dosimetric approaches based on different available imaging data have been reported. The aim of this work was to compare post-therapeutic 3D absorbed dose images using Technetium-99m (^99mTc) MAA SPECT/CT, Yttrium-90 (⁹⁰Y) bremsstrahlung (BRS) SPECT/CT, and ⁹⁰Y PET/CT.MethodsTen SIRTs of nine patients with unresectable hepatocellular carcinoma (HCC) were investigated. The ^99mTc SPECT/CT data, obtained from ^99mTc-MAA-based treatment simulation prior to ⁹⁰Y SIRT, were scaled with the administered ⁹⁰Y therapy activity. 3D absorbed dose images were generated by dose kernel convolution with scaled ^99mTc/⁹⁰Y SPECT/CT, ⁹⁰Y BRS SPECT/CT, and ⁹⁰Y PET/CT data of each patient. Absorbed dose estimates in tumor and healthy liver tissue obtained using the two SPECT/CT methods were compared against ⁹⁰Y PET/CT.ResultsThe percentage deviation of tumor absorbed dose estimates from ⁹⁰Y PET/CT values was on average −2 ± 18% for scaled ^99mTc/⁹⁰Y SPECT/CT, whereas estimates from ⁹⁰Y BRS SPECT/CT differed on average by −50 ± 13%. For healthy liver absorbed dose estimates, all three imaging methods revealed comparable values.ConclusionThe quantification capabilities of the imaging data influence ⁹⁰Y SIRT tumor dosimetry, while healthy liver absorbed dose values were comparable for all investigated imaging data. When no ⁹⁰Y PET/CT image data are available, the proposed scaled ^99mTc/⁹⁰Y SPECT/CT dosimetry method was found to be more appropriate for HCC tumor dosimetry than ⁹⁰Y BRS SPECT/CT based dosimetry.     

Synthesis of Tc-99m labeled glucosamino-Asp-cyclic(Arg-Gly-Asp-d-Phe-Lys) as a potential angiogenesis imaging agent

Angiogenesis imaging agents for single photon emission computed tomography (SPECT) play a role in diagnosing tumor-induced angiogenesis as well as tumor metastasis. We synthesized and evaluated radiolabeled RGD glycopeptides by incorporation of the [^99mTc(CO)₃(H₂O)₃]⁺. ^99mTc labeled glucosamino-D-c(RGDfK) ([^99mTc]2) was prepared in 90–93% radiochemical yields (decay corrected). In vitro cell binding assays demonstrated selective binding [^99mTc]2 to human umbilical vein endothelial (HUVE) cells, with inhibition of binding to 37.3% of control levels by 10 μM of cold authentic compounds. In addition, [^99mTc]2 was shown to have high binding affinity to purified α_vβ₃ integrin (IC₅₀ = 1.5 nM). These results suggest that these radiolabeled RGD glycopeptides may have value for non-invasive assessment of angiogenesis.     

Novel cancer-targeting SPECT/NIRF dual-modality imaging probe 99mTc-PC-1007: Synthesis and biological evaluation

Synthesis, characterization, in vitro and in vivo biological evaluation of a heptamethine cyanine based dual-mode single-photon emission computed tomography (SPECT)/near infrared fluorescence (NIRF) imaging probe ^99mTc-PC-1007 is described. ^99mTc-PC-1007 exhibited preferential accumulation in human breast cancer MCF-7 cells. Cancer-specific SPECT/CT and NIRF imaging of ^99mTc-PC-1007 was performed in a breast cancer xenograft model. The probe uptake ratio of tumor to control (spinal cord) was calculated to be 4.02 ± 0.56 at 6 h post injection (pi) and 8.50 ± 1.41 at 20 h pi (P < 0.0001). Pharmacokinetic parameters such as blood clearance and organ distribution were assessed.     

Évaluation de la cinétique globale et segmentaire du ventricule gauche chez les patients connus ou suspects de cardiopathie ischémique : comparaison des données apportées en scintigraphie de perfusion myocardique et en tomoventriculographie isotopique

Background and aimsThe analysis of the left ventricular contractile function plays a major role in the diagnosis and management of patients with cardiopathies. The aim of our study was to compare gated blood pool SPECT and myocardial perfusion scintigraphy for the assessment of the left ventricular wall contractility at the global and the segmental scales.Material and methodsThe data of 23 ^99mTc-Tetrofosmin perfusion scintigraphies, and 50 ²⁰¹Thallium perfusion scintigraphies were compared to those of gated blood pool SPECT performed at close interval.ResultsThe correlations were good (r = 0.81 to 0.94) concerning the global parameters (left ventricular ejection fraction, end-diastolic and end-systolic volumes) in the two groups. Quite good correlations were also found at the segmental scale (r = 0.49 to 0.62), between the segmental ejection fraction calculated in gated blood pool SPECT and the wall thickening or the wall motion estimated in perfusion scintigraphy. These correlations were significantly lower in the “²⁰¹Thallium perfusion scintigraphy” group than in the “^99mTc-Tetrofosmin perfusion scintigraphy” group, especially for hypokinetic segments.ConclusionAlthough they use very different approaches, GBPS and MPS give data about global and segmental left ventricular wall contraction that are well correlated, but not strictly interchangeable.     

Imagerie moléculaire dans les démences

Nuclear neuroimaging, with single photon emission computed tomography (SPECT) or with positron emission tomography (PET), allows study of functional and neurochemical aspects of human brain. It provides in vivo informations about pathophysiology in dementia. The routinely available tracers are perfusional tracers (^99mTc-HMPAO/GE Healthcare and ^99mTc-ECD/BMS). In June 2006, a new indication for the DaTSCAN^® (GE Healthcare) has been adopted. DaTSCAN^® could now be used to help differentiate probable dementia with Lewy bodies from Alzheimer's disease. Since a few years, there have been tremendous efforts expended to develop specific radioligands for several neurochemical systems and for imaging of beta-amyloid plaques. The aim of this paper is to review the most common radiotracers for SPECT and PET brain imaging in dementia and to focus on the new tracers.     

Synthesis and biological evaluation of a novel 99mTc cyclopentadienyl tricarbonyl complex ([(Cp-R)99mTc(CO)3]) for sigma-2 receptor tumor imaging

We report the design, synthesis and biological evaluation of a novel ^99mTc 4-(4-cyclohexylpiperazine-1-yl)-butan-1-one-1-cyclopentadienyltricarbonyl technetium ([^99mTc]5) as a potential SPECT tracer for imaging of σ₂ receptors in tumors. [^99mTc]5 was prepared in 25 ± 5% isolated radiochemical yield with radiochemical purity of >99% via double-ligand transfer (DLT) reaction from the ferrocene precursor 2b (4-(4-cyclohexylpiperazine-1-yl)-1-ferrocenylbutan-1-one). The corresponding Re-complex 4 and the ferrocenyl complex 2b showed relatively high affinity towards σ₂ receptors in in vitro competition binding assay (K_i values of 4 and 2b were 64.4 ± 18.5 nM and 43.6 ± 21.3 nM, respectively) and moderate to high selectivity versus σ₁ receptors (K_iσ₁/K_iσ₂ ratios were 12.5 and 95.5, respectively). The log D value of [^99mTc]5 was determined to be 2.52 ± 0.33. Biodistribution studies in mice revealed comparably high initial brain uptake of [^99mTc]5 and slow washout. Administration of haloperidol 5 min prior to injection of [^99mTc]5 significantly reduced the radiotracer uptake in brain, heart, lung, and spleen by 40–50% at 2 h p.i.. Moreover, [^99mTc]5 showed high uptake in C6 glioma cell lines (8.6%) after incubation for 1 h. Blocking with haloperidol to compete with [^99mTc]5 significantly reduced the cell uptake. Preliminary blocking study in C6-brain-tumor bearing rats showed that [^99mTc]5 binds to σ receptors in the brain-tumor specifically. These results are encouraging for further exploration of ^99mTc-labeled probes for σ₂ receptor tumor imaging in vivo.     

Effets de l’âge et du genre sur la perfusion cérébrale régionale étudiée par deux méthodes d’analyse statistique voxel-par-voxel

Fully automated analysis programs have been applied more and more to aid for the reading of regional cerebral blood flow SPECT study. They are increasingly based on the comparison of the patient study with a normal database. In this study, we evaluate the ability of Three-Dimensional Stereotactic Surface Projection (3D-SSP) to isolate effects of age and gender in a previously studied normal population. The results were also compared with those obtained using Statistical Parametric Mapping (SPM99).MethodsEighty-nine ^99mTc-ECD-SPECT studies performed in carefully screened healthy volunteers (46 females, 43 males; age 20–81 years) were analysed using 3D-SSP. A multivariate analysis based on the general linear model was performed with regions as intrasubject factor, gender as intersubject factor and age as covariate.ResultsBoth age and gender had a significant interaction effect with regional tracer uptake. An age-related decline (p < 0.001) was found in the anterior cingulate gyrus, left frontal association cortex and left insula. Bilateral occipital association and left primary visual cortical uptake showed a significant relative increase with age (p < 0.001). Concerning the gender effect, women showed higher uptake (p < 0.01) in the parietal and right sensorimotor cortices. An age by gender interaction (p < 0.01) was only found in the left medial frontal cortex. The results were consistent with those obtained with SPM99.Conclusion3D-SSP analysis of normal rCBF variability is consistent with the literature and other automated voxel-based techniques, which highlight the effects of both age and gender.     

Design,synthesis and structure–activity relationship of rhenium 2-arylbenzothiazoles as β-amyloid plaque binding agents

To continue our efforts toward the development of ^99mTc PiB analogs, we have synthesized 24 neutral and lipophilic Re (as a surrogate of ^99mTc) 2-arylbenzothiazoles, and explored their structure–activity relationship for binding to Aβ_1–40 fibrils. These Re complexes were designed and synthesized via the integrated approach, so their ^99mTc analogs would have a greater chance of crossing the blood–brain barrier. While the lipophilicities (log P_C18 = 1.59–3.53) of these Re 2-arylbenzothiazoles were all within suitable range, their binding affinities (K_i = 30–617 nM) to Aβ_1–40 fibrils varied widely depending on the selection and integration of the tetradentate chelator into the 2-phenylbenzothiazole pharmacophore. For potential clinical applications, further refinement to obtain Re 2-arylbenzothiazoles with better binding affinities (<10 nM) will likely be needed. The integrated approach reported here to generate compact, neutral and lipophilic Re 2-arylbenzothiazoles could be applied to other potent pharmacophores as well to convert other current Aβ PET tracers to their ^99mTc analogs for more widespread application via the use of SPECT scanners.     

99mTc-tricarbonyl labeled agents for cell labeling: Development,biodistribution in normal mice and preliminary in vitro evaluation

We have developed four ^99mTc(CO)₃-labeled lipophilic tracers as potential radiolabeling agents for cells based on a hexadecyl tail. ^99mTc(CO)₃-hexadecylamino-N,N′-diacetic acid (negatively charged), ^99mTc(CO)₃-hexadecylamino-N-α-picolyl-N′-acetic acid (uncharged), ^99mTc(CO)₃-N,N′-dipicolylhexadecylamine (positively charged), ^99mTc(CO)₃-N-hexadecylaminoethyl-N′-aminoethylamine (positively charged) were prepared in a radiolabeling yield: >90%. Preliminary cell uptake studies were performed in mixed blood cells with or without plasma and were compared with ^99mTc-d,l-HMPAO and [¹⁸F]FDG. In plasma-free blood cells, maximum uptake (78%) was obtained for ^99mTc(CO)₃-N-hexadecylaminoethyl-N′-aminoethylamine after 60 min incubation (compared to 55% and 23% for ^99mTc-d,l-HMPAO and [¹⁸F]FDG, respectively) while in plasma-rich medium, ^99mTc(CO)₃-N,N′-dipicolylhexadecylamine was best bound (54%, similar to the binding of ^99mTc-d,l-HMPAO). Biodistribution in normal mice showed mainly hepatobiliary clearance of the agents and initial high lung uptake. The radiolabeled compounds showed good blood clearance with maximally 7.9% injected dose per gram at 60 min post injection. While the least lipophilic agent (^99mTc(CO)₃-N,N′-dipicolylhexadecylamine, log P = 1.3) showed the best cell uptake, there appears to be no direct correlation between lipophilicity and tracer uptake in mixed blood cells. In view of its comparable cell uptake to well known cell labeling agent ^99mTc-d,l-HMPAO, ^99mTc(CO)₃-N,N′-dipicolylhexadecylamine merits further evaluation as a potential cell labeling agent.     

Synthesis and characterization of 123I-CMICE-013: A potential SPECT myocardial perfusion imaging agent

Coronary artery disease (CAD) is a major cause of death in Canada and the United States. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful diagnostic test in the management of patients with CAD. The widely used SPECT MPI agents, ^99mTc sestamibi and ^99mTc tetrofosmin, exhibit less than ideal pharmacokinetic properties with decreasing uptake with higher flows. ¹²³I has a similar energy as ^99mTc, an ideal half life, and is readily available from cyclotrons. The objective of this study was to develop an ¹²³I labeled MPI agent based on rotenone, a mitochondrial complex I inhibitor, as an alternative to currently available SPECT MPI agents. Methods: ¹²³I-CMICE-013 was synthesized by radiolabeling rotenone with ¹²³I in trifluoroacetic acid (TFA) with iodogen as the oxidizing agent at 60 °C for 45 min, followed by RP-HPLC purification. The product was formulated in 5% EtOH in 10 mM NaOAc pH 6.5. The inactive analog ¹²⁷I-CMICE-013 was isolated and characterized by NMR and mass spectrometry, and the structure determined. Micro-SPECT imaging studies were carried out in normal and infarcted rats. Biodistribution studies were performed in normal rats at 2 h (n = 6) and 24 h (n = 8) post injection (p.i.). Results: ¹²³I-CMICE-013 was isolated with >95% radiochemical purity and high specific activity (14.8–111 GBq/μmol; 400–3000 mCi/μmol). Structural analysis showed that rotenone was iodinated at 7′-position, with removal of the 6′,7′-double bond, and addition of a hydroxy group at 6′-position. MicroSPECT images in normal rats demonstrated homogeneous and sustained myocardial uptake with minimal interference from lung and liver. Absent myocardial perfusion was clearly identified in rats with permanent left coronary artery ligation and ischemia-reperfusion injury. In vivo biodistribution studies in normal rats at 2 h p.i. showed significant myocardial uptake (2.01 ± 0.48%ID/g) and high heart to liver (2.98 ± 0.93), heart to lung (4.11 ± 1.04) and heart to blood (8.37 ± 3.97) ratios. At 24 h p.i., the majority of ¹²³I-CMICE-013 was cleared from tissues, and a significant amount of tracer was found in the thyroid, indicating in vivo deiodination of the tracer. Conclusion: ¹²³I-CMICE-013 is a promising new radiotracer for SPECT MPI with high myocardial uptake, very good target to background ratios and favorable biodistribution characteristics.     

Synthesis and β-amyloid binding properties of rhenium 2-phenylbenzothiazoles

As a first step toward the development of ^99mTc PiB analogs, we have synthesized six neutral Re 2-phenylbenzothiazoles via pendant or integrated approach. These Re compounds bind to Aβ_1–40 fibrils with fairly good affinities (K_i = 10.0–88.6 nM) and have moderate lipophilicities (log P_C18 = 1.21–3.26). The Re compounds prepared via the integrated approach are smaller in size, and therefore their corresponding ^99mTc analogs would have a greater chance of crossing the blood-brain barrier well. For potential clinical applications, further optimization on the structure–activity relationship to obtain Re 2-phenylbenzothiazoles with higher binding affinities (<10 nM) might be needed. The integrated approach reported here to obtain neutral, compact and lipophilic Re 2-phenylbenzothiazoles could to be applied to other high affinity pharmacophores as well as to generate ^99mTc analogs that could hold promise for extending the use of Aβ imaging in living human brain to many more clinical settings because they could be used with SPECT.     

Preparation of classical Re/99mTc(CO)3+ and novel 99mTc(CO)2(NO)2+ cores complexed with flavonol derivatives and their binding characteristics for Aβ(1–40) aggregates

Classical ^99mTc(CO)₃⁺ and novel ^99mTc(CO)₂(NO)²⁺ cores complexed with flavonol derivatives were prepared. Autoradiography of postmortem AD transgenic mice (Tg C57, APP, PS1 12-month-old) brain section confirmed the binding property of [^99mTc(CO)₃⁺-3-OH-flavone]⁰ to Aβ_(1–40) aggregates, while the novel ^99mTc(CO)₂(NO)²⁺ labeled compounds showed no binding sites in AD transgenic mice sections. Intravenous administration of [^99mTc(CO)₃⁺-3-OH-flavone]⁰ resulted in moderate brain uptake (0.48 ± 0.05%ID/g) at 5 min post-injection and slow clearance from the brain issues in 2 h post-injection (120 min: 0.39 ± 0.08%ID/g). Then an Aβ_(1–40)-receptor-targeted Re(CO)₃⁺-3-OH-flavone, was prepared to identify the structure of the technetium complex. UV–vis absorption and fluorescence emission properties have been studied at room temperature in order to determine the natures of the lowest electronically excited states of Re(CO)₃⁺-3-OH-flavone and the ligand. The fluorescent rhenium complex Re(CO)₃⁺-3-OH-flavone showed high affinity for Aβ_(1–40) aggregates in vitro by fluorescence spectra (dissociation constant (K_d) = 11.16 nM). In conclusion, the results suggested that ^99mTc(CO)₃⁺-3-OH-flavone should be a suitable candidate as Aβ plaque SPECT imaging agent for AD.     

Infection de prothèse vasculaire : TEP-FDG vs scintigraphie aux leucocytes marqués (planaires et TEMP/TDM)

Vascular prosthesis infection is an uncommon but life-threatening complication. Its diagnosis is difficult to establish especially due to the low specificity of computed tomography (CT). The aim of this preliminary study was to compare the diagnostic value of positron emission tomography with¹⁸FDG (¹⁸FDG-PET) and ^99mTc-HMPAO-labeled leukocytes scintigraphy in this indication. ¹⁸FDG-PET/CT and ^99mTc-HMPAO-labeled leukocytes scintigraphy (planar at 6th and 24th hours after injection + SPECT/CT at the 6th hour) were prospectively performed in 11 patients (total of 22 vascular prosthesis with 14 clinical suspicions of infection). Both scans were retrospectively and blindly assessed by two independent nuclear medicine physicians. Interpretation was based on visual analysis. The gold standard was bacteriology findings or clinical follow-up greater than 6 months. Eight prostheses were considered as infected. PET found eight true-positive and one false-positive. Scintigraphy found eight true-positive and no false-positive. A focal or heterogeneous FDG-uptake higher or equal than hepatic uptake was considered as positive in PET. A focal prosthetic activity, stable or increased at the 24th hour was considered as positive in labeled leukocyte scintigraphy. SPECT/CT gave accurate anatomic localization and differentiated clearly infections of soft tissues from those of prostheses. ¹⁸FDG-PET could be performed in first-line in suspicion of vascular prosthesis infection. In litigious cases, a^99mTc-HMPAO-labeled leukocytes scintigraphy in association with SPECT/CT could bring additional arguments for infection diagnosis.     

Capillary electrophoresis of 99mtechnetium radiopharmaceuticals

Diagnostically used ^99mTc kit radiopharmaceuticals were analyzed using capillary zone electrophoresis with radioactivity detection: ^99mTc-bis(bis(2-ethyloxyethyl)phosphino)ethane (^99mTc-Myoview, ^99mTc-Tetrofosmin), ^99mTc-trans(1,2-bis(dehydro-2,2,5,5,-tetramethyl-3-furanone-4-methylene-amino)ethane)-tris(3-methoxy-1-propyl)phosphine) (^99mTc-Technescan Q12, ^99mTc-Furifosmin), ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI), ^99mTc-l,l-ethylenecysteine diethylester dimer (^99mTc-ECD), ^99mTc-d,l-hexamethylene propyleneamine oxime (^99mTc-HMPAO), ^99mTc-diethylenetriaminepentaacetic acid (^99mTc-DTPA), ^99mTc-ethylene hepatobiliary iminodiacetic acid (^99mTc-EHIDA), ^99mTc-l,l-ethylenecysteine dimer (^99mTc-EC), ^99mTc-mercaptoacetylglycylglycylglycine (^99mTc-MAG₃), ^99mTc-dimercaptosuccinic acid (^99mTc-DMSA), ^99mTc-methylene diphosphonate (^99mTc-MDP) and ^99mNaTcO₄. A pressure-driven capillary zone electrophoresis was employed to detect small anions of high electrophoretic mobility and cations within one run. Effective ^99mTc complex charges could be determined by a neutral internal standard. All complexes showed the expected electrophoretic behaviours in view of their charges. Pure products were obtained for the majority of the studied complexes. In the case of ^99mTc-Q12, ^99mTc-EHIDA and ^99mTc-MDP, complex mixtures were detected. The high potential of CE for the analysis of ^99mTc radiopharmaceuticals could be shown.     

Segmentation and Visual Analysis of Whole-Body Mouse Skeleton microSPECT

Whole-body SPECT small animal imaging is used to study cancer, and plays an important role in the development of new drugs. Comparing and exploring whole-body datasets can be a difficult and time-consuming task due to the inherent heterogeneity of the data (high volume/throughput, multi-modality, postural and positioning variability). The goal of this study was to provide a method to align and compare side-by-side multiple whole-body skeleton SPECT datasets in a common reference, thus eliminating acquisition variability that exists between the subjects in cross-sectional and multi-modal studies. Six whole-body SPECT/CT datasets of BALB/c mice injected with bone targeting tracers ^99mTc-methylene diphosphonate (^99mTc-MDP) and ^99mTc-hydroxymethane diphosphonate (^99mTc-HDP) were used to evaluate the proposed method. An articulated version of the MOBY whole-body mouse atlas was used as a common reference. Its individual bones were registered one-by-one to the skeleton extracted from the acquired SPECT data following an anatomical hierarchical tree. Sequential registration was used while constraining the local degrees of freedom (DoFs) of each bone in accordance to the type of joint and its range of motion. The Articulated Planar Reformation (APR) algorithm was applied to the segmented data for side-by-side change visualization and comparison of data. To quantitatively evaluate the proposed algorithm, bone segmentations of extracted skeletons from the correspondent CT datasets were used. Euclidean point to surface distances between each dataset and the MOBY atlas were calculated. The obtained results indicate that after registration, the mean Euclidean distance decreased from 11.5±12.1 to 2.6±2.1 voxels. The proposed approach yielded satisfactory segmentation results with minimal user intervention. It proved to be robust for “incomplete” data (large chunks of skeleton missing) and for an intuitive exploration and comparison of multi-modal SPECT/CT cross-sectional mouse data.