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Razifar, Pasha
Publications (7 of 7) Show all publications
Hall, H., Takahashi, K., Erlandsson, M., Estrada, S., Razifar, P., Bergström, E. & Långström, B. (2012). Pharmacological characterization of 18F-labeled vorozole analogs. Journal of labelled compounds & radiopharmaceuticals, 55(14), 484-490
Open this publication in new window or tab >>Pharmacological characterization of 18F-labeled vorozole analogs
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2012 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 55, no 14, p. 484-490Article in journal (Refereed) Published
Abstract [en]

Two F-18-labeled analogs of vorozole ([F-18]FVOZ and [F-18]FVOO) have been developed as potential tools for the in vivo characterization of aromatase. The pharmacologicalproperties of these radioligands were evaluated using in vitro binding and in vivo distribution studies in the rat and primate. Saturation binding studies using rat ovary gave K-D and B-max values of 0.21 +/- 0.1 nM and 210 +/- 20 fmol/mg, respectively, for [F-18]FVOZ, and 7.6 +/- 1nMand 293 +/- 12fmol/mg, respectively, for [F-18]FVOO. Organ distribution studies in rats showed the highest accumulation in the adrenal glands, with standardized uptake values (SUVs) of 15 to 20, followed by ovaries and liver with SUVs of approximately 5. Ex vivo and in vitro autoradiography of the rat brain showed specific binding of both [F-18]FVOZ and [F-18]FVOO mainly in the amygdala. Positron emission tomography (PET) studies were performed in the Rhesus monkey, and these showed displaceable binding in the amygdala and the hypothalamus preoptic area. The PET images were also analyzed using masked volume-wise principal component analysis. These studies suggest that [F-18]FVOZ might be a suitable tracer for the study of aromatase in vitro and in vivo, and could be an alternative to [C-11]vorozole in human PET studies.

National Category
Radiology, Nuclear Medicine and Medical Imaging Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-189515 (URN)10.1002/jlcr.2982 (DOI)000314069900002 ()
Available from: 2012-11-20 Created: 2013-01-02 Last updated: 2017-12-06Bibliographically approved
Blom, E., Velikyan, I., Monazzam, A., Razifar, P., Nair, M., Razifar, P., . . . Långström, B. (2011). Synthesis and characterization of scVEGF-PEG-[68Ga]NOTA and scVEGF-PEG-[68Ga]DOTA PET tracers. Journal of labelled compounds & radiopharmaceuticals, 54(11), 685-692
Open this publication in new window or tab >>Synthesis and characterization of scVEGF-PEG-[68Ga]NOTA and scVEGF-PEG-[68Ga]DOTA PET tracers
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2011 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 54, no 11, p. 685-692Article in journal (Refereed) Published
Abstract [en]

Vascular endothelial growth factor (VEGF) signaling via vascular endothelial growth factor receptor 2 (VEGFR-2) on tumor endothelial cells is a critical driver of tumor angiogenesis. Novel anti-angiogenic drugs target VEGF/VEGFR-2 signaling and induce changes in VEGFR-2 prevalence. To monitor VEGFR-2 prevalence in the course of treatment, we are evaluating (68)Ga positron emission tomography imaging agents based on macrocyclic chelators, site-specifically conjugated via polyethylene glycol (PEG) linkers to engineered VEGFR-2 ligand, single-chain (sc) VEGF. The (68)Ga-labeling was performed at room temperature with NOTA (2,2', 2 ''-(1,4,7-triazonane-1,4,7-triyl) triacetic acid) conjugates or at 90 degrees C by using either conventional or microwave heating with NOTA and DOTA (2,2', 2 '', 2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid) conjugates. The fastest (similar to 2min) and the highest incorporation (>90%) of (68)Ga into conjugate that resulted in the highest specific radioactivity (similar to 400MBq/nmol) was obtained with microwave heating of the conjugates. The bioactivity of the NOTA-and DOTA-containing tracers was validated in 3-D tissue culture model of 293/KDR cells engineered to express high levels of VEGFR-2. The NOTA-containing tracer also displayed a rapid accumulation (similar to 20s after intravenous injection) to steady-state level in xenograft tumor models. A combination of high specific radioactivity and maintenance of functional activity suggests that scVEGF-PEG-[(68)Ga] NOTA and scVEGF-PEG-[(68)Ga] DOTA might be promising tracers for monitoring VEGFR-2 prevalence and should be further explored.

Keywords
scVEGF, (68)Ga, radiolabeling, angiogenesis, VEGFR-2, PET
National Category
Organic Chemistry Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-108589 (URN)10.1002/jlcr.1909 (DOI)000297987200001 ()
Available from: 2009-10-10 Created: 2009-09-23 Last updated: 2017-12-13Bibliographically approved
Razifar, P., Hennings, J., Monazzam, A., Hellman, P., Långström, B. & Sundin, A. (2009). Masked volume wise Principal Component Analysis of small adrenocortical tumours in dynamic [11C]-metomidate Positron Emission Tomography. BMC Medical Imaging, 9:6
Open this publication in new window or tab >>Masked volume wise Principal Component Analysis of small adrenocortical tumours in dynamic [11C]-metomidate Positron Emission Tomography
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2009 (English)In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 9:6Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality. METHODS: In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate-PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO-PET was performed before and 3 days after starting per oral cortisone treatment. The whole dataset, reconstructed by filtered back projection (FBP) 0-45 minutes after the tracer injection, was used to study the tracer pharmacokinetics. RESULTS: Early, intermediate and late pharmacokinetic phases could be isolated in this manner. The MVW-PC1 images correlated well to the conventionally summed image data (15-45 minutes) but the image noise in the former was considerably lower. PET measurements performed by defining "hot spot" regions of interest (ROIs) comprising 4 contiguous pixels with the highest radioactivity concentration showed a trend towards higher SUVs when the ROIs were outlined in the MVW-PC1 component than in the summed images. Time activity curves derived from "50% cut-off" ROIs based on an isocontour function whereby the pixels with SUVs between 50 to 100% of the highest radioactivity concentration were delineated, showed a significant decrease of the SUVs in normal adrenal glands and in adrenocortical adenomas after cortisone treatment. CONCLUSION: In addition to the clear decrease in image noise and the improved contrast between different structures with MVW-PCA, the results indicate that the definition of ROIs may be more accurate and precise in MVW-PC1 images than in conventional summed images. This might improve the precision of PET measurements, for instance in therapy monitoring as well as for delineation of the tumour in radiation therapy planning.

National Category
Radiology, Nuclear Medicine and Medical Imaging Medical Image Processing
Research subject
Computerized Image Analysis
Identifiers
urn:nbn:se:uu:diva-104646 (URN)10.1186/1471-2342-9-6 (DOI)19386097 (PubMedID)
Available from: 2009-04-22 Created: 2009-05-29 Last updated: 2017-12-13Bibliographically approved
Monazzma, A., Razifar, P., Simonsson, M., Qvarnström, F., Josephsson, R., Blomqvist, C., . . . Bergström, M. (2006). Multicellular Tumour Spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring. Cancer Cell International, 6, 6
Open this publication in new window or tab >>Multicellular Tumour Spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring
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2006 (English)In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 6, p. 6-Article in journal (Refereed) Published
Abstract [en]

Background

In order to explore a pre-clinical method to evaluate if [18F]FDG is valid for monitoring early response, we investigated the uptake of FDG in Multicellular tumour spheroids (MTS) without and with treatment with five routinely used chemotherapy agents in breast cancer.

Methods

The response to each anticancer treatment was evaluated by measurement of the [18F]FDG uptake and viable volume of the MTSs after 2 and 3 days of treatment.

Results

The effect of Paclitaxel and Docetaxel on [18F]FDG uptake per viable volume was more evident in BT474 (up to 55% decrease) than in MCF-7 (up to 25% decrease).

Doxorubicin reduced the [18F]FDG uptake per viable volume more noticeable in MCF-7 (25%) than in BT474 MTSs.

Tamoxifen reduced the [18F]FDG uptake per viable volume only in MCF-7 at the highest dose of 1 μM.

No effect of Imatinib was observed.

Conclusion

MTS was shown to be appropriate to investigate the potential of FDG-PET for early breast cancer treatment monitoring; the treatment effect can be observed before any tumour size changes occur.

The combination of PET radiotracers and image analysis in MTS provides a good model to evaluate the relationship between tumour volume and the uptake of metabolic tracer before and after chemotherapy. This feature could be used for screening and selecting PET-tracers for early assessment of treatment response.

In addition, this new method gives a possibility to assess quickly, and in vitro, a good preclinical profile of existing and newly developed anti-cancer drugs.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-96169 (URN)10.1186/1475-2867-6-6 (DOI)
Available from: 2007-09-12 Created: 2007-09-12 Last updated: 2018-11-13
Monazzam, A., Razifar, P., Lindhe, Ö., Josephsson, R., Långström, B. & Bergström, M. (2005). A new, fast and semi-automated size determination method (SASDM) for studying multicellular tumor spheroids. Cancer Cell International (5), 32
Open this publication in new window or tab >>A new, fast and semi-automated size determination method (SASDM) for studying multicellular tumor spheroids
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2005 (English)In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, no 5, p. 32-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Considering the width and importance of using Multicellular Tumor Spheroids (MTS) in oncology research, size determination of MTSs by an accurate and fast method is essential. In the present study an effective, fast and semi-automated method, SASDM, was developed to determinate the size of MTSs. The method was applied and tested in MTSs of three different cell-lines. Frozen section autoradiography and Hemotoxylin Eosin (H&E) staining was used for further confirmation.

RESULTS:

SASDM was shown to be effective, user-friendly, and time efficient, and to be more precise than the traditional methods and it was applicable for MTSs of different cell-lines. Furthermore, the results of image analysis showed high correspondence to the results of autoradiography and staining.

CONCLUSION:

The combination of assessment of metabolic condition and image analysis in MTSs provides a good model to evaluate the effect of various anti-cancer treatments.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-96168 (URN)10.1186/1475-2867-5-32 (DOI)16283948 (PubMedID)
Available from: 2007-09-12 Created: 2007-09-12 Last updated: 2017-12-14Bibliographically approved
Razifar, P., Sandström, M., Schneider, H., Långström, B., Maripuu, E., Bengtsson, E. & Bergström, M. (2005). Noise correlation in PET, CT, SPECT and PET/CT data evaluated using autocorrelation function: a phantom study on data, reconstructed using FBP and OSEM.. Bio Medical Central (BMC): Medical Imaging, 5(5)
Open this publication in new window or tab >>Noise correlation in PET, CT, SPECT and PET/CT data evaluated using autocorrelation function: a phantom study on data, reconstructed using FBP and OSEM.
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2005 (English)In: Bio Medical Central (BMC): Medical Imaging, Vol. 5, no 5Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Positron Emission Tomography (PET), Computed Tomography (CT), PET/CT and Single Photon Emission Tomography (SPECT) are non-invasive imaging tools used for creating two dimensional (2D) cross section images of three dimensional (3D) objects. PET and SPECT have the potential of providing functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules, whereas CT visualizes X-ray density in tissues in the body. PET/CT provides fused images representing both functional and anatomical information with better precision in localization than PET alone.Images generated by these types of techniques are generally noisy, thereby impairing the imaging potential and affecting the precision in quantitative values derived from the images. It is crucial to explore and understand the properties of noise in these imaging techniques. Here we used autocorrelation function (ACF) specifically to describe noise correlation and its non-isotropic behaviour in experimentally generated images of PET, CT, PET/CT and SPECT. METHODS: Experiments were performed using phantoms with different shapes. In PET and PET/CT studies, data were acquired in 2D acquisition mode and reconstructed by both analytical filter back projection (FBP) and iterative, ordered subsets expectation maximisation (OSEM) methods. In the PET/CT studies, different magnitudes of X-ray dose in the transmission were employed by using different mA settings for the X-ray tube. In the CT studies, data were acquired using different slice thickness with and without applied dose reduction function and the images were reconstructed by FBP. SPECT studies were performed in 2D, reconstructed using FBP and OSEM, using post 3D filtering. ACF images were generated from the primary images, and profiles across the ACF images were used to describe the noise correlation in different directions. The variance of noise across the images was visualised as images and with profiles across these images. RESULTS: The most important finding was that the pattern of noise correlation is rotation symmetric or isotropic, independent of object shape in PET and PET/CT images reconstructed using the iterative method. This is, however, not the case in FBP images when the shape of phantom is not circular. Also CT images reconstructed using FBP show the same non-isotropic pattern independent of slice thickness and utilization of care dose function. SPECT images show an isotropic correlation of the noise independent of object shape or applied reconstruction algorithm. Noise in PET/CT images was identical independent of the applied X-ray dose in the transmission part (CT), indicating that the noise from transmission with the applied doses does not propagate into the PET images showing that the noise from the emission part is dominant. The results indicate that in human studies it is possible to utilize a low dose in transmission part while maintaining the noise behaviour and the quality of the images. CONCLUSION: The combined effect of noise correlation for asymmetric objects and a varying noise variance across the image field significantly complicates the interpretation of the images when statistical methods are used, such as with statistical estimates of precision in average values, use of statistical parametric mapping methods and principal component analysis. Hence it is recommended that iterative reconstruction methods are used for such applications. However, it is possible to calculate the noise analytically in images reconstructed by FBP, while it is not possible to do the same calculation in images reconstructed by iterative methods. Therefore for performing statistical methods of analysis which depend on knowing the noise, FBP would be preferred.

National Category
Computer Vision and Robotics (Autonomous Systems)
Identifiers
urn:nbn:se:uu:diva-74266 (URN)10.1186/1471-2342-5-5 (DOI)
Available from: 2005-09-19 Created: 2005-09-19 Last updated: 2018-01-14
Razifar, P., Lubberink, M., Schneider, H., Långström, B., Bengtsson, E. & Bergström, M. (2005). Non-isotropic noise correlation in PET data reconstructed by FBP but not by OSEM demonstrated using auto-correlation function. Bio Medical Central (BMC): Medical Imaging, 5(3)
Open this publication in new window or tab >>Non-isotropic noise correlation in PET data reconstructed by FBP but not by OSEM demonstrated using auto-correlation function
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2005 (English)In: Bio Medical Central (BMC): Medical Imaging, Vol. 5, no 3Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Positron emission tomography (PET) is a powerful imaging technique with the potential of obtaining functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules in a biological system, both in vitro and in vivo. PET images can be used directly or after kinetic modelling to extract quantitative values of a desired physiological, biochemical or pharmacological entity. Because such images are generally noisy, it is essential to understand how noise affects the derived quantitative values. A pre-requisite for this understanding is that the properties of noise such as variance (magnitude) and texture (correlation) are known. METHODS: In this paper we explored the pattern of noise correlation in experimentally generated PET images, with emphasis on the angular dependence of correlation, using the autocorrelation function (ACF). Experimental PET data were acquired in 2D and 3D acquisition mode and reconstructed by analytical filtered back projection (FBP) and iterative ordered subsets expectation maximisation (OSEM) methods. The 3D data was rebinned to a 2D dataset using FOurier REbinning (FORE) followed by 2D reconstruction using either FBP or OSEM. In synthetic images we compared the ACF results with those from covariance matrix. The results were illustrated as 1D profiles and also visualized as 2D ACF images. RESULTS: We found that the autocorrelation images from PET data obtained after FBP were not fully rotationally symmetric or isotropic if the object deviated from a uniform cylindrical radioactivity distribution. In contrast, similar autocorrelation images obtained after OSEM reconstruction were isotropic even when the phantom was not circular. Simulations indicated that the noise autocorrelation is non-isotropic in images created by FBP when the level of noise in projections is angularly variable. Comparison between 1D cross profiles on autocorrelation images obtained by FBP reconstruction and covariance matrices produced almost identical results in a simulation study. CONCLUSION: With asymmetric radioactivity distribution in PET, reconstruction using FBP, in contrast to OSEM, generates images in which the noise correlation is non-isotropic when the noise magnitude is angular dependent, such as in objects with asymmetric radioactivity distribution. In this respect, iterative reconstruction is superior since it creates isotropic noise correlations in the images.

National Category
Computer Vision and Robotics (Autonomous Systems)
Identifiers
urn:nbn:se:uu:diva-74268 (URN)10.1186/1471-2342-5-3 (DOI)
Available from: 2005-09-19 Created: 2005-09-19 Last updated: 2018-01-14
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