3D melanoma spheroid model for the development of positronium biomarker
H. Karimi, P. Moskal, E.Ł. Stępień
abstract
It was recently demonstrated that newly invented positronium imaging may be used for improving cancer diagnostics by providing additional information about tissue pathology with respect to the standardized uptake value currently available in positron emission tomography (PET). Positronium imaging utilizes properties of a positronium atoms, which are built from the electron and positron produced in the body during PET examinations.
We hypothesized whether positronium imaging would be sensitive to in vitro discrimination of tumour-like three-dimensional structures (spheroids) build of melanoma cell lines with different cancer activity and biological properties.
The lifetime of ortho-Positronium (o-Ps) was evaluated in melanoma spheroids from two cell lines (WM266-4 and WM115) differing in the stage of malignancy. Additionally, we considered such parameters: as cell size, proliferation rate and malignancy to evaluate their relationship with o-Ps lifetime. We demonstrate the pilot results for the o-Ps lifetime measurement in extracellular matrix free spheroids. With the statistical significance of two standard deviations, we demonstrated that the higher the degree of malignancy and the rate of proliferation of neoplastic cells the shorter the lifetime of ortho-positronium. In particular we observed following indications encouraging further research: (i) WM266-4 spheroids characterized with higher proliferation rate and malignancy showed shorter o-Ps lifetime compared to WM115 spheroids characterized by lower growth rate, (ii) Both cell lines showed a decrease in the lifetime of o-Ps after spheroid generation in 8th day comparing to 4th day in culture and the mean o-Ps lifetime is longer for spheroids formed from WM115 cells than these from WM266-4 cells, regardless spheroid age. The results of these study revealed that positronium is a promising biomarker that may be applied in PET diagnostics for the assessment of the degree of cancer malignancy.
Positronium imaging with the novel multiphoton PET scanner
P. Moskal, K. Dulski, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, J. Gajewski, A. Gajos, G. Grudzień, B.C. Hiesmayr, K. Kacprzak, Ł. Kapłon, H. Karimi, K. Klimaszewski, G. Korcyl, P. Kowalski, T. Kozik, N. Krawczyk, W. Krzemień, E. Kubicz, P. Małczak, S. Niedźwiecki, M. Pawlik-Niedźwiecka, M. Pędziwiatr, L. Raczyński, J. Raj, A. Ruciński, S. Sharma, Shivani, R.Y. Shopa, M. Silarski, M. Skurzok, E.Ł. Stępień, M. Szczepanek, F. Tayefi, W. Wiślicki
abstract
In vivo assessment of cancer and precise location of altered tissues at initial stages of molecular disorders are important diagnostic challenges. Positronium is copiously formed in the free molecular spaces in the patient?s body during positron emission tomography (PET). The positronium properties vary according to the size of inter- and intramolecular voids and the concentration of molecules in them such as, e.g., molecular oxygen, O2; therefore, positronium imaging may provide information about disease progression during the initial stages of molecular alterations. Current PET systems do not allow acquisition of positronium images. This study presents a new method that enables positronium imaging by simultaneous registration of annihilation photons and deexcitation photons from pharmaceuticals labeled with radionuclides. The first positronium imaging of a phantom built from cardiac myxoma and adipose tissue is demonstrated. It is anticipated that positronium imaging will substantially
enhance the specificity of PET diagnostics.
Testing CPT symmetry in ortho-positronium decays with positronium annihilation tomography
P. Moskal, A. Gajos, M. Mohammed, J. Chhokar, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, M. Gorgol, J. Goworek, B. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, D. Kisielewska, K. Klimaszewski, G. Korcyl, P. Kowalski, N. Krawczyk, W. Krzemień, T. Kozik, E. Kubicz, S. Niedźwiecki, S. Parzych, M. Pawlik-Niedźwiecka, L. Raczyński, J. Raj, S. Sharma, S. Choudhary, R. Shopa, A. Sienkiewicz, M. Silarski, M. Skurzok, E. Stepien, F. Tayefi, W. Wiślicki
abstract
Charged lepton system symmetry under combined charge, parity, and time-reversal transformation (CPT) remain scarcely tested. Despite stringent quantum-electrodynamic limits, discrepancies in predictions for the electron-positron bound state (positronium atom) motivate further investigation, including fundamental symmetry tests. While CPT noninvariance effects could be manifested in non-vanishing angular correlations between final-state photons and spin of annihilating positronium, measurements were previously limited by the knowledge of the latter. Here, we demonstrate tomographic reconstruction techniques applied to three-photon annihilations of ortho-positronium atoms to estimate their spin polarisation without a magnetic field or polarised positronium source. We use a plastic-scintillator-based positron-emission-tomography scanner to record ortho-positronium (o-Ps) annihilations with a single-event estimation of o-Ps spin and determine the complete spectrum of an angular correlation operator sensitive to CPT-violating effects. We find no violation at the precision level of 10^{-4}, with an over threefold improvement on the previous measurement.
The J-PET detector - a tool for precision studies of ortho-positronium decays
K. Dulski, S.D. Bass, J. Chhokar, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, J. Gajewski, A. Gajos, M. Gorgol, R. Del Grande, B.C. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, D. Kisielewska, K. Klimaszewski, P. Kopka, G. Korcyl, P. Kowalski, T. Kozik, N. Krawczyk, W. Krzemień, E. Kubicz, P. Małczak, M. Mohammed, Sz. Niedźwiecki, M. Pałka, M. Pawlik-Niedźwiecka, M. Pędziwiatr, L. Raczyński7, J. Raj, A. Ruciński, S. Sharma, Shivani, R.Y. Shopa, M. Silarski, M. Skurzok, E. Ł. Stępień, F. Tayefi, W. Wiślicki, B. Zgardzińska, P. Moskal
abstract
The J-PET tomograph is constructed from plastic scintillator strips arranged axially in concentric cylindrical layers. It enables investigations of positronium decays by measurement of the time, position, polarization and energy deposited by photons in the scintillators, in contrast to studies conducted so far with crystal and semiconductor based detection systems where the key selection of events is based on the measurement of the photons energies. In this article we show that the J-PET tomography system constructed solely from plastic scintillator detectors is capable of exclusive measurements of the decays of ortho-positronium atoms. We present the first positronium production results and its lifetime distribution measurements. The obtained results prove the capability of the J-PET tomograph for (i) fundamental studies of positronium decays (in particular test of discrete symmetries in purely leptonic systems), (ii) positron annihilation lifetime spectroscopy, as well as (iii) molecular imaging diagnostics and (iv) observation of entanglement
Synchronisation and calibration of the 24-modules J-PET prototype with 300 mm axial field of view
P. Moskal, T. Bednarski, Sz. Niedźwiecki, M. Silarski, E. Czerwiński, T. Kozik, J. Chhokar, M. Bała, C. Curceanu, R. Del Grande, M. Dadgar, K. Dulski, A. Gajos, M. Gorgol, N. Gupta-Sharma, B. C. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, D. Kisielewska, K.Klimaszewski, G. Korcyl, P. Kowalski, N. Krawczyk, W. Krzemień, E. Kubicz, M. Mohammed, M. Pawlik-Niedźwiecka, L. Raczyński, S. Sharma, Shivani, R. Y. Shopa, M. Skurzok, E. Stępień, W. Wiślicki, B. Zgardzińska
abstract
Research conducted in the framework of the J-PET project aims to develop a cost-effective total-body positron emission tomography scanner. As a first step on the way to construct a full-scale J-PET tomograph from long strips of plastic scintillators, a 24-strip prototype was built and tested. The prototype consists of detection modules arranged axially forming a cylindrical diagnostic chamber with an inner diameter of 360 mm and an axial field-of-view of 300 mm. Promising perspectives for a low-cost construction of a total-body PET scanner are opened due to an axial arrangement of strips of plastic scintillators, which have a small light attenuation, superior timing properties, and the possibility of cost-effective increase of the axial field-of-view. The presented prototype comprises dedicated solely digital front-end electronic circuits and a triggerless data acquisition system which required development of new calibration methods including time, thresholds and gain synchronization. The system and elaborated calibration methods including first results of the 24-module J-PET prototype are presented and discussed. The achieved coincidence resolving time equals to CRT = 490 +- 9 ps. This value can be translated to the position reconstruction accuracy s(Dl) = 18 mm which is fairly position-independent Keywords: positron emission tomography, plastic scintillators, J-PET.
X-ray microtomography as a new approach for imaging and analysis of tumor spheroids
H. Karimi, B. Leszczyński, T. Kołodziej, E. Kubicz, M. Przybyło, E. Stępień
abstract
Three-dimensional (3D) spheroids mimic important properties of tumors and may soon become a reasonable
substitute for animal models and human tissue, eliminating numerous problems related to in vivo and ex vivo
experiments and pre-clinical drug trials. Currently, various imaging methods including X-ray microtomography
(micro-CT), exist but their spatial resolution is limited. Here, we visualized and provided a morphological
analysis of spheroid cell cultures using micro-CT and compared it to that of confocal microscopy. An approach is
proposed that can potentially open new diagnostic opportunities to determine the morphology of cancer cells
cultured in 3D structures instead of using actual tumors.
Spheroids were formed from human melanoma cell lines WM266-4 and WM115 seeded at different cell
densities using the hanging drop method. Micro-CT analysis of spheroid showed that spheroid size and shape
differed depending on the cell line, initial cell number, and duration of culture.
The melanoma cell lines used in this study can successfully be cultured as 3D spheroids and used to substitute
human and animal models in pre-clinical studies. The micro-CT allows for high-resolution visualization of the
spheroids structure.
Performance assessment of the 2gamma positronium imaging with the total-body PET scanners
P. Moskal, D. Kisielewska, Z. Bura, C. Chhokar, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, J. Gajewski, A. Gajos, M. Gorgol, R. Del Grande, B. C. Hiesmayr, B. Jasińska, K. Kacprzak, A. Kamińska, Ł. Kapłon, H. Karimi, G. Korcyl, P. Kowalski, N. Krawczyk, W. Krzemień, T. Kozik, E. Kubicz, P. Małczak, M. Mohammed, Sz. Niedźwiecki, M. Pałka, M. Pawlik-Niedźwiecka, M. Pędziwiatr, L. Raczyński, J. Raj, A. Ruciński, S. Sharma, Shivani, R. Y. Shopa, M. Silarski, M. Skurzok, E. Ł. Stępień, S. Vandenberghe, W. Wiślicki, B. Zgardzińska
abstract
In living organisms the positron-electron annihilation (occurring during the PET imaging) proceeds in about 30% via creation of a metastable ortho-positronium atom. In the tissue, due to the pick-off and conversion processes, over 98% of ortho-positronia annihilate into two 511~keV photons. In this article we assess the feasibility for reconstruction of the mean ortho-positronium lifetime image based on annihilations into two photons. The main objectives of this work include: (i) estimation of the sensitivity of the total-body PET scanners for the ortho-positronium mean lifetime imaging using 2gamma annihilations, and (ii) estimation of the spatial and time resolution of the ortho-positronium image as a function of the coincidence resolving time (CRT) of the scanner. Simulations are conducted assuming that radiopharmaceutical is labelled with 44Sc isotope emitting one positron and one prompt gamma. The image is reconstructed on the basis of triple coincidence events. The ortho-positronium lifetime spectrum is determined for each voxel of the image. Calculations were performed for cases of total-body detectors build of (i) LYSO scintillators as used in the EXPLORER PET, and (ii) plastic scintillators as anticipated for the cost-effective total-body J-PET scanner. To assess the spatial and time resolution the three cases were considered assuming that CRT is equal to 140ps, 50ps and 10ps. The estimated total-body PET sensitivity for the registration and selection of image forming triple coincidences is larger by a factor of 12.2 (for LYSO PET) and by factor of 4.7 (for plastic PET) with respect to the sensitivity for the standard 2gamma imaging by LYSO PET scanners with AFOV=20cm.
Estimating relationship between the Time Over Threshold and energy loss by photons in plastic scintillators used in the J-PET scanner
S. Sharma, J. Chhokar, C. Curceanu, E. Czerwinski, M. Dadgar, K. Dulski, J. Gajewski, A. Gajos, M. Gorgol, N. Gupta-Sharma, R. Del Grande, B. C. Hiesmayr, B. Jasinska, K. Kacprzak, L. Kaplon, H. Karimi, D. Kisielewska, K. Klimaszewski, G. Korcyl, P. Kowalski, T. Kozik, N. Krawczyk, W. Krzemien, E. Kubicz, M. Mohammed, Sz. Niedzwiecki, M. Palka, M. Pawlik-Niedzwiecka, L. Raczynski, J. Raj, A. Rucinski, Shivani, R. Y. Shopa, M. Silarski, M. Skurzok, E. L. Stepien, W. Wislicki, B. Zgardzinska, P. Moskal
abstract
Time-Over-Threshold (TOT) technique is being used widely due to its implications in developing the multi channel readouts mainly when fast signal processing is required. Using TOT technique as a measure of energy loss instead of charge integration methods significantly reduces the signals readout cost by combining the time and energy information. Therefore, this approach can potentially be used in J-PET tomograph which is build from plastic scintillators characterized by fast light signals. The drawback in adopting this technique is lying in the non-linear correlation between input energy loss and TOT of the signal. The main motivation behind this work is to develop the relationship between TOT and energy loss and validate it with the J-PET tomograph.
The experiment was performed using the 22Na beta emitter source placed in the center of the J-PET tomograph. One can obtain primary photons of two different energies: 511 keV photon from the annihilation of positron (direct annihilation or through the formation of para-Positronim atom or pick-off process of ortho-Positronium atoms), and 1275 keV prompt photon. This allows to study the correlation between TOT values and energy loss for energy range up to 1000 keV. As the photon interacts dominantly via Compton scattering inside the plastic scintillator, there is no direct information of primary photon energy. However, using the J-PET geometry one can measure the scattering angle of the interacting photon. Since, 22Na source emits photons of two different energies, it is required to know unambiguously the energy of incident photons and its corresponding scattering angle for the estimation of energy deposition. In this work, the relationship between Time Over Threshold and energy loss by interacting photons inside the plastic scintillators used in J-PET scanner is established for a energy deposited range 100-1000 keV.
Melanoma spheroids as a model for cancer imaging study
E. Ł. Stępień, H. Karimi, B. Leszczyński, M. Szczepanek
abstract
In contrast to standard 2D cell cultures, spheroids are three-dimensional (3D) models which can mimic natural conditions of cancer growth and metabolism. Their complex structure can be investigated and analyzed using fluorescence microscopy and micro-tomographic imaging (micro-CT) as a new technique. In this study, we show application of two different melanoma cell lines (WM115 and WM266) with different biological characteristics to form spheroids by a hanging drop method.
New approach to visualize 3 dimensional cancer cells
Hanieh Karimi , Bartosz Leszczyński , Ewa Stępień, Pawel Moskal
3rd Jagiellonian Symposium on Fundamental a nd Applied Subatomic Physics, Cracow, Poland, June 2019
Towards molecular in-vivo cancer imaging by means of positronium and the J-PET tomograph
P. Moskal, M. Bała, Z. Bura, J.Chhokar, M. Dadgar, K. Dulski, K.Farbaniec, A. Gajos, B. Jasińska, H. Karimi, E. Kubicz, G. Korcyl, K. Rakoczy, S. Sharma, E.Stępień
FNP IIIrd Inter Deciplinary Congress meeting, April 11, 2019, Warsaw, Poland
Radiochemical Evaluation and In Vitro Assessment of the Targeting Ability of a Novel 99mTc-HYNIC-RGD for U87MG Human Brain Cancer Cells
Hanieh Karimi , Nourollah Sadeghzadeh , Saeid Abediankenari , Farzaneh Rezazadeh ,Fereshteh Hallajian
3rd Symposium on positron emission tomography, Cracow, Poland
Radio chemical Evaluation and In Vitro Assessment of the Targeting Ability of a Novel 99mTc-HYNIC-RGD for U87MG Human Brain Cancer Cells
Hanieh Karimi, Nourollah Sadeghzadeh, Fereshteh Hallajian
3rd Symposium on positron emission tomography
Radiochemical Evaluation and In Vitro Assessment of the Targeting Ability of a Novel 99mTc-HYNIC-RGD for U87MG Human Brain Cancer Cells
Hanieh Karimi , Nourollah Sadeghzadeh , Saeid Abediankenari , Farzaneh Rezazadeh ,Fereshteh Hallajian
2nd Workshop on neutrons in medicine and homeland security
