Concomitant [18F]F-FAZA and [18F]F-FDG Imaging of Gynecological Cancer Xenografts: Insight into Tumor Hypoxia.

BACKGROUND/AIM: Herein we assessed the feasibility of imaging protocols using both hypoxia-specific [18F]F-FAZA and [18F]F-FDG in bypassing the limitations derived from the non-specific findings of [18F]F-FDG PET imaging of tumor-related hypoxia. MATERIALS AND METHODS: CoCl2-generated hypoxia was induced in multidrug resistant (Pgp+) or sensitive (Pgp-) human ovarian (Pgp- A2780, Pgp+ A2780AD), and cervix carcinoma (Pgp- KB-3-1, Pgp+ KB-V-1) cell lines to establish corresponding tumor-bearing mouse models. Prior to [18F]F-FDG/[18F]F-FAZA-based MiniPET imaging, in vitro [18F]F-FDG uptake measurements and western blotting were used to verify the presence of hypoxia. RESULTS: Elevated GLUT-1, and hexokinase enzyme-II expression driven by CoCl2-induced activation of hypoxia-inducible factor-1α explains enhanced cellular [18F]F-FDG accumulation. No difference was observed in the [18F]F-FAZA accretion of Pgp+ and Pgp- tumors. Tumor-to-muscle ratios for [18F]F-FAZA measured at 110-120 min postinjection (6.2±0.1) provided the best contrasted images for the delineation of PET-oxic and PET-hypoxic intratumor regions. Although all tumors exhibited heterogenous uptake of both radiopharmaceuticals, greater differences for [18F]F-FAZA between the tracer avid and non-accumulating regions indicate its superiority over [18F]F-FDG. Spatial correlation between [18F]F-FGD and [18F]F-FAZA scans confirms that hypoxia mostly occurs in regions with highly active glucose metabolism. CONCLUSION: The addition of [18F]F-FAZA PET to [18F]F-FGD imaging may add clinical value in determining hypoxic sub-regions.

Phantom Study on the Robustness of MR Radiomics Features: Comparing the Applicability of 3D Printed and Biological Phantoms.

The objectives of our study were to (a) evaluate the feasibility of using 3D printed phantoms in magnetic resonance imaging (MR) in assessing the robustness and repeatability of radiomic parameters and (b) to compare the results obtained from the 3D printed phantoms to metrics obtained in biological phantoms. To this end, three different 3D phantoms were printed: a Hilbert cube (5 × 5 × 5 cm3) and two cubic quick response (QR) code phantoms (a large phantom (large QR) (5 × 5 × 4 cm3) and a small phantom (small QR) (4 × 4 × 3 cm3)). All 3D printed and biological phantoms (kiwis, tomatoes, and onions) were scanned thrice on clinical 1.5 T and 3 T MR with 1 mm and 2 mm isotropic resolution. Subsequent analyses included analyses of several radiomics indices (RI), their repeatability and reliability were calculated using the coefficient of variation (CV), the relative percentage difference (RPD), and the interclass coefficient (ICC) parameters. Additionally, the readability of QR codes obtained from the MR images was examined with several mobile phones and algorithms. The best repeatability (CV ≤ 10%) is reported for the acquisition protocols with the highest spatial resolution. In general, the repeatability and reliability of RI were better in data obtained at 1.5 T (CV = 1.9) than at 3 T (CV = 2.11). Furthermore, we report good agreements between results obtained for the 3D phantoms and biological phantoms. Finally, analyses of the read-out rate of the QR code revealed better texture analyses for images with a spatial resolution of 1 mm than 2 mm. In conclusion, 3D printing techniques offer a unique solution to create textures for analyzing the reliability of radiomic data from MR scans.

3D printed anthropomorphic left ventricular myocardial phantom for nuclear medicine imaging applications.

BACKGROUND: Anthropomorphic torso phantoms, including a cardiac insert, are frequently used to investigate the imaging performance of SPECT and PET systems. These phantom solutions are generally featuring a simple anatomical representation of the heart. 3D printing technology paves the way to create cardiac phantoms with more complex volume definition. This study aimed to describe how a fillable left ventricular myocardium (LVm) phantom can be manufactured using geometry extracted from a patient image. METHODS: The LVm of a healthy subject was segmented from 18F-FDG attenuation corrected PET image set. Two types of phantoms were created and 3D printed using polyethylene terephthalate glycol (PETG) material: one representing the original healthy LVm, and the other mimicking myocardium with a perfusion defect. The accuracy of the LVm phantom production was investigated by high-resolution CT scanning of 3 identical replicas. 99mTc SPECT acquisitions using local cardiac protocol were performed, without additional scattering media ("in air" measurements) for both phantom types. Furthermore, the healthy LVm phantom was inserted in the commercially available DataSpectrum Anthropomorphic Torso Phantom ("in torso" measurement) and measured with hot background and hot liver insert. RESULTS: Phantoms were easy to fill without any air-bubbles or leakage, were found to be reproducible and fully compatible with the torso phantom. Seventeen segments polar map analysis of the "in air" measurements revealed that a significant deficit in the distribution appeared where it was expected. 59% of polar map segments had less than 5% deviation for the "in torso" and "in air" measurement comparison. Excluding the deficit area, neither comparison had more than a 12.4% deviation. All the three polar maps showed similar apex and apical region values for all configurations. CONCLUSIONS: Fillable anthropomorphic 3D printed phantom of LVm can be produced with high precision and reproducibility. The 3D printed LVm phantoms were found to be suitable for SPECT image quality tests during different imaging scenarios. The flexibility of the 3D printing process presented in this study provides scalable and anthropomorphic image quality phantoms in nuclear cardiology imaging.

In Vivo Imaging of Ischemia/Reperfusion-mediated Aminopeptidase N Expression in Surgical Rat Model Using 68Ga-NOTA-c(NGR).

BACKGROUND/AIM: Previous studies have already shown that 68Gallium(68Ga)-labeled NGR-based radiopharmaceuticals specifically bind to the neoangiogenic molecule Aminopeptidase N (APN/CD13). The aim of this study was to evaluate the applicability of 68Ga-NOTA-c(NGR) in the in vivo detection of the temporal changes of APN/CD13 expression in the diabetic retinopathy rat model using positron emission tomography (PET). MATERIALS AND METHODS: Ischemia/reperfusion injury was initiated by surgical ligation of the left bulbus oculi of rats. In vivo PET imaging studies were performed after the surgery using 68Ga-NOTA-c(NGR). RESULTS: Significantly higher 68Ga-NOTA-c(NGR) uptake was observed in the surgically-ligated left bulbus, compared to the bulbus of the non-surgical group at each investigated time point. The western blot and histological analysis confirmed the increased expression of the neo-angiogenic marker APN/CD13. CONCLUSION: 68Ga-NOTA-c(NGR) is a suitable radiotracer for the detection of the temporal changes of the ischemia/reperfusion-mediated expression of APN/CD13 in the surgically induced diabetic retinopathy rat model.

Automated procedure assessing the accuracy of HRCT-PET registration applied in functional virtual bronchoscopy.

BACKGROUND: Bronchoscopy serves as direct visualisation of the airway. Virtual bronchoscopy provides similar visual information using a non-invasive imaging procedure(s). Early and accurate image-guided diagnosis requires the possible highest performance, which might be approximated by combining anatomical and functional imaging. This communication describes an advanced functional virtual bronchoscopic (fVB) method based on the registration of PET images to high-resolution diagnostic CT images instead of low-dose CT images of lower resolution obtained from PET/CT scans. PET/CT and diagnostic CT data were collected from 22 oncological patients to develop a computer-aided high-precision fVB. Registration of segmented images was performed using elastix. RESULTS: For virtual bronchoscopy, we used an in-house developed segmentation method. The quality of low- and high-dose CT image registrations was characterised by expert's scoring the spatial distance of manually paired corresponding points and by eight voxel intensity-based (dis)similarity parameters. The distribution of (dis)similarity parameter correlating best with anatomic scoring was bootstrapped, and 95% confidence intervals were calculated separately for acceptable and insufficient registrations. We showed that mutual information (MI) of the eight investigated (dis)similarity parameters displayed the closest correlation with the anatomy-based distance metrics used to characterise the quality of image registrations. The 95% confidence intervals of the bootstrapped MI distribution were [0.15, 0.22] and [0.28, 0.37] for insufficient and acceptable registrations, respectively. In case of any new patient, a calculated MI value of registered low- and high-dose CT image pair within the [0.28, 0.37] or the [0.15, 0.22] interval would suggest acceptance or rejection, respectively, serving as an aid for the radiologist. CONCLUSION: A computer-aided solution was proposed in order to reduce reliance on radiologist's contribution for the approval of acceptable image registrations.

Effect of grey-level discretization on texture feature on different weighted MRI images of diverse disease groups.

PURPOSE: Many studies of MRI radiomics do not include the discretization method used for the analyses, which might indicate that the discretization methods used are considered irrelevant. Our goals were to compare three frequently used discretization methods (lesion relative resampling (LRR), lesion absolute resampling (LAR) and absolute resampling (AR)) applied to the same data set, along with two different lesion segmentation approaches. METHODS: We analyzed the effects of altering bin widths or bin numbers for the three different sampling methods using 40 texture indices (TIs). The impact was evaluated on brain MRI studies obtained for 71 patients divided into three different disease groups: multiple sclerosis (MS, N = 22), ischemic stroke (IS, N = 22), cancer patients (N = 27). Two different MRI acquisition protocols were considered for all patients, a T2- and a post-contrast 3D T1-weighted MRI sequence. Elliptical and manually drawn VOIs were employed for both imaging series. Three different types of gray-level discretization methods were used: LRR, LAR and AR. Hypothesis tests were done among all diseased and control areas to compare the TI values in these areas. We also did correlation analyses between TI values and lesion volumes. RESULTS: In general, no significant differences were reported in the results when employing the AR and LAR discretization methods. It was found that employing 38 TIs introduced variation in the results when the number of bin parameters was altered, suggesting that both the degree and direction of monotonicity between each TI value and binning parameters were characteristic for each TI. Furthermore, while TIs were changing with altering binning values, no changes correlated to neither disease nor the MRI sequence. We found that most indices correlated weakly with the volume, while the correlation coefficients were independent of both diseases analyzed and MR contrast. Several cooccurrence-matrix based texture parameters show a definite higher correlation when employing the LRR discretization method However, with the best correlations obtained for the manually drawn VOI. Hypothesis tests among all disease and control areas (co-lateral hemisphere) revealed that the AR or LAR discretization techniques provide more suitable texture features than LRR. In addition, the manually drawn segmentation gave fewer significantly different TIs than the ellipsoid segmentations. In addition, the amount of TIs with significant differences was increasing with increasing the number of bins, or decreasing bin widths. CONCLUSION: Our findings indicate that the AR discretization method may offer the best texture analysis in MR image assessments. Employing too many bins or too large bin widths might reduce the selection of TIs that can be used for differential diagnosis. In general, more statistically different TIs were observed for elliptical segmentations when compared to the manually drawn VOIs. In the texture analysis of MR studies, studies and publications should report on all important parameters and methods related to data collection, corrections, normalization, discretization, and segmentation.

Q-Bot: automatic DICOM metadata monitoring for the next level of quality management in nuclear medicine.

BACKGROUND: Regular and precise inspection of the realization of the local nuclear medicine standard operation procedures (SOPs) is very complex and time-consuming, especially when large amount of patient data is obtained from a wide scale of different scan procedures on a daily basis. DICOM metadata comprise a complete set of data related to the patient and the imaging procedure, and consequently all information necessary to evaluate the compliance with the actual SOP. METHODS: Q-Bot, an automatic DICOM metadata monitoring tool which is capable to verify SOP conformities, was tested for 11 months at two nuclear medicine departments. Relevant parameters, such as patient ID, patient mass and height, injected activity, and uptake time, were investigated in the case of adult 18F-FDG whole-body PET/CT and 99mTc-MDP gamma camera bone scans on a daily basis. Q-Bot automatically inspected the actual SOP compliance of these relevant DICOM parameters. Q-Bot graphical user interface (GUI) provided a summary of the outliers in a table format to be investigated by a dedicated technologist. In addition, information related to the error handling was also collected for retrospective analysis of long-term tendencies. RESULTS: In total, 6702 PET/CT and 2502 gamma camera scans were inspected, from which 8581 were confirmed as valid patient study without errors. Discrepancies related to the lack of a parameter, not appropriate format, or improper scan procedures were found in 623 cases, and 156 out of these were corrected before the medical reading and reporting. SOP non-conformities explored with Q-Bot were found to be non-correctable in 467 cases. Systematic errors to our practice turned out to be the manual radiopharmaceutical injection, the allowance to use both SI and non-SI units, and the clear definition of decimal point symbol to use. CONCLUSION: The daily evaluation of Q-Bot results provided early detection of errors and consequently ensured the minimization of error propagation. Integration of a QM software that inspects protocol compliance at a nuclear medicine department provides significant support to detect non-conformities for technologists, and much higher confidence in image quality for physicians.

[Methods and feasibilities of texture analysis in PET diagnostics]. / A textúraanalízis módszere és lehetoségei a PET-diagnosztikában.

One of the current research objectives of medical imaging is to determine the prognostic value of tumor textures and related numerical values. In PET/CT studies the diagnostic and prognostic values of specific texture parameters were confirmed at several tumor types (lung, prostate, cervix, colon, head and neck). However, the results are often contradictory, various publications find different texture parameters useful for the same tumor type. The reason for the contradictions is partly methodological, since the definition and the calculation of texture data is a multi-step process. Such steps include scan protocol, image reconstruction, tumor segmentation, re-sampling the voxel values and the form of texture algorithms. Recent publications show that by harmonizing these steps, the prognostic power and reliability of the texture features can be improved. The most optimal way of harmonization would be a special phantom application that could simulate inhomogeneous distributions typical for tumor tissues, with high reproducibility.

Impact of intensity discretization on textural indices of [18F]FDG-PET tumour heterogeneity in lung cancer patients.

Quantifying tumour heterogeneity from [18F]FDG-PET images promises benefits for treatment selection of cancer patients. Here, the calculation of texture parameters mandates an initial discretization step (binning) to reduce the number of intensity levels. Typically, three types of discrimination methods are used: lesion relative resampling (LRR) with fixed bin number, lesion absolute resampling (LAR) and absolute resampling (AR) with fixed bin widths. We investigated the effects of varying bin widths or bin number using 27 commonly cited local and regional texture indices (TIs) applied on lung tumour volumes. The data set were extracted from 58 lung cancer patients, with three different and robust tumour segmentation methods. In our cohort, the variations of the mean value as the function of the bin widths were similar for TIs calculated with LAR and AR quantification. The TI histograms calculated by LRR method showed distinct behaviour and its numerical values substantially effected by the selected bin number. The correlations of the AR and LAR based TIs demonstrated no principal differences between these methods. However, no correlation was found for the interrelationship between the TIs calculated by LRR and LAR (or AR) discretization method. Visual classification of the texture was also performed for each lesion. This classification analysis revealed that the parameters show statistically significant correlation with the visual score, if LAR or AR discretization method is considered, in contrast to LRR. Moreover, all the resulted tendencies were similar regardless the segmentation methods and the type of textural features involved in this work.

Activity painting: PET images of freely defined activity distributions applying a novel phantom technique.

The aim of this work was to develop a novel phantom that supports the construction of highly reproducible phantoms with arbitrary activity distributions for PET imaging. It could offer a methodology for answering questions related to texture measurements in PET imaging. The basic idea is to move a point source on a 3-D trajectory in the field of view, while continuously acquiring data. The reconstruction results in a 3-D activity concentration map according to the pathway of the point source. A 22Na calibration point source was attached to a high precision robotic arm system, where the 3-D movement was software controlled. 3-D activity distributions of a homogeneous cube, a sphere, a spherical shell and a heart shape were simulated. These distributions were used to measure uniformity and to characterize reproducibility. Two potential applications using the lesion simulation method are presented: evaluation in changes of textural properties related to the position in the PET field of view; scanner comparison based on visual and quantitative evaluation of texture features. A lesion with volume of 50x50x50 mm3 can be simulated during approximately 1 hour. The reproducibility of the movement was found to be >99%. The coefficients of variation of the voxels within a simulated homogeneous cube was 2.34%. Based on 5 consecutive and independent measurements of a 36 mm diameter hot sphere, the coefficient of variation of the mean activity concentration was 0.68%. We obtained up to 18% differences within the values of investigated textural indexes, when measuring a lesion in different radial positions of the PET field of view. In comparison of two different human PET scanners the percentage differences between heterogeneity parameters were in the range of 5-55%. After harmonizing the voxel sizes this range reduced to 2-16%. The general activity distributions provided by the two different vendor show high similarity visually. For the demonstration of the flexibility of this method, the same pattern was also simulated on a small animal PET scanner giving similar results, both quantitatively and visually. 3-D motion of a point source in the PET field of view is capable to create an irregular shaped activity distribution with high reproducibility.

2D and 3D texture analysis to differentiate brain metastases on MR images: proceed with caution.

OBJECTIVE: To find structural differences between brain metastases of lung and breast cancer, computing their heterogeneity parameters by means of both 2D and 3D texture analysis (TA). MATERIALS AND METHODS: Patients with 58 brain metastases from breast (26) and lung cancer (32) were examined by MR imaging. Brain lesions were manually delineated by 2D ROIs on the slices of contrast-enhanced T1-weighted (CET1) images, and local binary patterns (LBP) maps were created from each region. Histogram-based (minimum, maximum, mean, standard deviation, and variance), and co-occurrence matrix-based (contrast, correlation, energy, entropy, and homogeneity) 2D, weighted average of the 2D slices, and true 3D TA were obtained on the CET1 images and LBP maps. RESULTS: For LBP maps and 2D TA contrast, correlation, energy, and homogeneity were identified as statistically different heterogeneity parameters (SDHPs) between lung and breast metastasis. The weighted 3D TA identified entropy as an additional SDHP. Only two texture indexes (TI) were significantly different with true 3D TA: entropy and energy. All these TIs discriminated between the two tumor types significantly by ROC analysis. For the CET1 images there was no SDHP at all by 3D TA. CONCLUSION: Our results indicate that the used textural analysis methods may help with discriminating between brain metastases of different primary tumors.

A Study on the Basic Criteria for Selecting Heterogeneity Parameters of F18-FDG PET Images.

Textural analysis might give new insights into the quantitative characterization of metabolically active tumors. More than thirty textural parameters have been investigated in former F18-FDG studies already. The purpose of the paper is to declare basic requirements as a selection strategy to identify the most appropriate heterogeneity parameters to measure textural features. Our predefined requirements were: a reliable heterogeneity parameter has to be volume independent, reproducible, and suitable for expressing quantitatively the degree of heterogeneity. Based on this criteria, we compared various suggested measures of homogeneity. A homogeneous cylindrical phantom was measured on three different PET/CT scanners using the commonly used protocol. In addition, a custom-made inhomogeneous tumor insert placed into the NEMA image quality phantom was imaged with a set of acquisition times and several different reconstruction protocols. PET data of 65 patients with proven lung lesions were retrospectively analyzed as well. Four heterogeneity parameters out of 27 were found as the most attractive ones to characterize the textural properties of metabolically active tumors in FDG PET images. These four parameters included Entropy, Contrast, Correlation, and Coefficient of Variation. These parameters were independent of delineated tumor volume (bigger than 25-30 ml), provided reproducible values (relative standard deviation< 10%), and showed high sensitivity to changes in heterogeneity. Phantom measurements are a viable way to test the reliability of heterogeneity parameters that would be of interest to nuclear imaging clinicians.

The Effect of Passive Movement for Paretic Ankle-Foot and Brain Activity in Post-Stroke Patients.

BACKGROUND: This study aims at investigating the short-term efficacy of the continuous passive motion (CPM) device developed for the therapy of ankle-foot paresis and to investigate by fMRI the blood oxygen level-dependent responses (BOLD) during ankle passive movement (PM). METHODS: Sixty-four stroke patients were investigated. Patients were assigned into 2 groups: 49 patients received both 15 min manual and 30 min device therapy (M + D), while the other group (n = 15) received only 15 min manual therapy (M). A third group of stroke patients (n = 12) was investigated by fMRI before and immediately after 30 min CPM device therapy. There was no direct relation between the fMRI group and the other 2 groups. All subjects were assessed using the Modified Ashworth Scale (MAS) and a goniometer. RESULTS: Mean MAS decreased, the ankle's mean plantar flexion and dorsiflexion passive range of motion (PROM) increased and the equinovalgus improved significantly in the M + D group. In the fMRI group, the PM of the paretic ankle increased BOLD responses; this was observed in the contralateral pre- and postcentral gyrus, superior temporal gyrus, central opercular cortex, and in the ipsilateral postcentral gyrus, frontal operculum cortex and cerebellum. CONCLUSION: Manual therapy with CPM device therapy improved the ankle PROM, equinovalgus and severity of spasticity. The ankle PM increased ipsi- and contralateral cortical activation.

A Promising Future: Comparable Imaging Capability of MRI-Compatible Silicon Photomultiplier and Conventional Photosensor Preclinical PET Systems.

UNLABELLED: We recently completed construction of a small-animal PET system-the MiniPET-3-that uses state-of-the-art silicon photomultiplier (SiPM) photosensors, making possible dual-modality imaging with MRI. In this article, we compare the MiniPET-3 with the MiniPET-2, a system with the same crystal geometry but conventional photomultiplier tubes (PMTs). METHODS: The standard measurements proposed by the National Electrical Manufacturers Association NU 4 protocols were performed on both systems. These measurements included spatial resolution, system sensitivity, energy resolution, counting rate performance, scatter fraction, spillover ratio for air and water, recovery coefficient, and image uniformity. The energy windows were set to 350-650 keV on the MiniPET-2 and 360-662 keV on the MiniPET-3. RESULTS: Spatial resolution was approximately 17% better on average for the MiniPET-3 than the MiniPET-2. The systems performed similarly in terms of peak absolute sensitivity (∼1.37%), spillover ratio for air (∼0.15), spillover ratio for water (∼0.25), and recovery coefficient (∼0.33, 0.59, 0.81, 0.89, and 0.94). Uniformity was 5.59% for the MiniPET-2 and 6.49% for the MiniPET-3. Minor differences were found in scatter fraction. With the ratlike phantom, the peak noise-equivalent counting rate was 14 kcps on the MiniPET-2 but 24 kcps on the MiniPET-3. However, with the mouselike phantom, these values were 55 and 91 kcps, respectively. The optimal coincidence time window was 6 ns for the MiniPET-2 and 8 ns for the MiniPET-3. CONCLUSION: Images obtained with the SiPM-based MiniPET-3 small-animal PET system are similar in quality to those obtained with the conventional PMT-based MiniPET-2.

[New trends and novel possibilities in functional medical imaging: imaging methods]. / Újdonságok és új lehetoségek a funkcionális képalkotásban: Leképezéstechnikai újdonságok.

The aim of the study is to review the new tomographic imaging technologies which enable to investigate the metabolic activity of the human body. Accordingly, we overview the current promising methodology in the field of PET and SPECT, but we will also mention interesting applications at the area of MRI and CT.

Wall motion changes in myocardial infarction in relation to the time elapsed from symptoms until revascularization.

OBJECTIVE: Wall motion abnormalities during acute ST-segment elevation myocardial infarction (STEMI) and the improvement after recanalization depend on the conditions of the coronary occlusion. METHODS: Fifty-seven patients with first-ever STEMI due to one-artery occlusion, treated with primary PCI, were evaluated. Area at risk and left ventricular wall motion abnormalities were localized with coronary angiography and echocardiography and then compared in relation to the time elapsed from the onset of symptoms at the time of infarction and at 3 months. Left ventricular diameters and ejection fractions were evaluated in relation to the ischemic time. RESULTS: Three hundred forty-one affected left ventricular segments were detected with angiography, while echocardiography showed 206 segments with motion abnormality. No correlation was found between the regional wall motion index in the area at risk and the time elapsed from the beginning of symptoms. However, the improvement in wall motion abnormalities at the follow-up was dependent on the ischemic time (r=-0.29, p<0.03). The early subgroup showed significant improvement in left ventricular ejection fraction at follow-up (p=0.03), whereas in the late subgroup, a significant increase in left ventricle diameters was observed. CONCLUSION: Our results first demonstrate in humans that in the early hours from the occlusion of the coronary artery, the extent and severity of the wall motion abnormalities inside the area at risk show large variability without relation to the elapsed time since the onset of symptoms. On the other hand, the results of follow-up echocardiography proved that the wall motion improvement was highly dependent on the ischemic time.

[New trends in functional medical imaging: quantitative methods]. / Újdonságok és új lehetoségek a funkcionális képalkotásban: kvantitatív módszerek.

Deriving quantitative measures from the medical imaging methods is a key issue for the optimal oncologic therapy, when the anatomical abnormalities and changes of the metabolic state of the tissues need to be characterized. In order to improve the effectiveness of the therapy, the results of medical imaging procedures should be comparable after two or more consecutive scans. There are several tomographic imaging applications (CT, MRI, SPECT and PET), but in this work we will focus on the quantitative capability of PET, because this method provides the most versatile possibilities for quantifying the resulting images.

18FDG, [18F]FLT, [18F]FAZA, and 11C-methionine are suitable tracers for the diagnosis and in vivo follow-up of the efficacy of chemotherapy by miniPET in both multidrug resistant and sensitive human gynecologic tumor xenografts.

Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG), (11)C-methionine, 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT), and [(18)F]fluoroazomycin-arabinofuranoside ((18)FAZA) for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp(+)) and negative (Pgp(-)) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp(+) and Pgp(-) A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp(+) tumors. Our results demonstrate that (18)FDG, (18)F-FLT, (18)FAZA, and (11)C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp(+) and Pgp(-) human tumor xenografts by miniPET.

Excel2Genie: A Microsoft Excel application to improve the flexibility of the Genie-2000 Spectroscopic software.

Excel2Genie, a simple and user-friendly Microsoft Excel interface, has been developed to the Genie-2000 Spectroscopic Software of Canberra Industries. This Excel application can directly control Canberra Multichannel Analyzer (MCA), process the acquired data and visualize them. Combination of Genie-2000 with Excel2Genie results in remarkably increased flexibility and a possibility to carry out repetitive data acquisitions even with changing parameters and more sophisticated analysis. The developed software package comprises three worksheets: display parameters and results of data acquisition, data analysis and mathematical operations carried out on the measured gamma spectra. At the same time it also allows control of these processes. Excel2Genie is freely available to assist gamma spectrum measurements and data evaluation by the interested Canberra users. With access to the Visual Basic Application (VBA) source code of this application users are enabled to modify the developed interface according to their intentions.

¹8FDG a PET tumor diagnostic tracer is not a substrate of the ABC transporter P-glycoprotein.

2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) is a tumor diagnostic radiotracer of great importance in both diagnosing primary and metastatic tumors and in monitoring the efficacy of the treatment. P-glycoprotein (Pgp) is an active transporter that is often expressed in various malignancies either intrinsically or appears later upon disease progression or in response to chemotherapy. Several authors reported that the accumulation of (18)FDG in P-glycoprotein (Pgp) expressing cancer cells (Pgp(+)) and tumors is different from the accumulation of the tracer in Pgp nonexpressing (Pgp(-)) ones, therefore we investigated whether (18)FDG is a substrate or modulator of Pgp pump. Rhodamine 123 (R123) accumulation experiments and ATPase assay were used to detect whether (18)FDG is substrate for Pgp. The accumulation and efflux kinetics of (18)FDG were examined in two different human gynecologic (A2780/A2780AD and KB-3-1/KB-V1) and a mouse fibroblast (3T3 and 3T3MDR1) Pgp(+) and Pgp(-) cancer cell line pairs both in cell suspension and monolayer cultures. We found that (18)FDG and its derivatives did not affect either the R123 accumulation in Pgp(+) cells or the basal and the substrate stimulated ATPase activity of Pgp supporting that they are not substrates or modulators of the pump. Measuring the accumulation and efflux kinetics of (18)FDG in different Pgp(+) and Pgp(-) cell line pairs, we have found that the Pgp(+) cells exhibited significantly higher (p⩽0.01) (18)FDG accumulation and slightly faster (18)FDG efflux kinetics compared to their Pgp(-) counterparts. The above data support the idea that expression of Pgp may increase the energy demand of cells resulting in higher (18)FDG accumulation and faster efflux. We concluded that (18)FDG and its metabolites are not substrates of Pgp.