A new detector concept based on the prompt gamma radiation analysis for In vivo boron monitoring in BNCT
M. Silarski, K. Dziedzic-Kocurek, F. Sobczuk, A. Nykiel, P. Moskal, S. Niedźwiecki, E.Ł. Stępień, M. Szczepanek
abstract
The problem of boron concentration monitoring during the boron neutron capture therapy (BNCT) therapy is one of the main challenges of this type of radiotherapy and is directly related to the nature of the interaction of neutrons with mater. Among the available in vivo methods of boron monitoring positron emission tomography seems to be very promising but it requires a new boron carrier with a ?+ emitter, which is not yet clinically available. An alternative solution may be the prompt gamma radiation analysis (PGRA) based on the secondary radiation emitted in the interaction of neutrons with the patient's tissues. This method requires, however, compact gamma radiation detection systems sustaining high counting rates and characterized by very good energy resolution. In this contribution, we present state-of-the-art solutions for monitoring in BNCT based on PGRA. Moreover, we describe a new concept of such a system based on position-sensitive scintillator detectors equipped with an anti-Compton shield and data analysis supported with modern artificial intelligence algorithms.
Transcriptomic data analysis of melanocytes and melanoma cell lines of LAT transporter genes for precise medicine
M. Szczepanek, D. Panek, M. Przybyło, P. Moskal, E. Stępień
abstract
Background: Boron Neutron Capture Therapy (BNCT) is a two-step treatment that can be used in some types of cancers. It involves administering a compound containing boron atoms to the patient and irradiating the affected area of the body with a neutron beam. The success of the therapy depends mainly on the delivery of the boron isotope (10B) to the tumor using an appropriate boron carrier. One of the boron carriers used is boronophenylalanine (BPA). Therefore, in research on the use of boron carriers, it is also important to know the mechanisms of its uptake by cells. Aim: To study the expression of LAT family genes in two melanoma (high melanotic WM115 and low melanotic WM266-4) cell lines and melanocytes (HEMa-Lp) which are responsible for the transport the BPA into cells. Methods: To normalize data from the transcriptomic analysis, the ratio of the median method was used. This allowed the samples to be compared with each other. Comparison metrics included log-fold change (LFC) values. The heatmap of LFC values and the cluster map were created. These graphs show the similarities and differences between the samples. Results: Transcriptomic data show that in melanocytes, LFC for SLC7A5 (LAT1) and SLC3A2 (4Fhc) was higher than in melanoma cell lines, which corresponded with their melanin content. Conclusion: Our results indicate overexpression of BPA transporter genes in normal cells (melanocytes), which may suggest the highest level of these proteins in melanocytes compared to less melanotic melanoma. Therefore, for BNCT, the use of BPA as the 10B carrier will require additional qualifying tests of amino acid transporter expression for patients and specific tumors to develop a personalized BNCT.
Comparison of Lugol's solution and Fe3O4 nanoparticles as contrast agents for tumor spheroid imaging using microcomputed tomography
D. Panek, M. Szczepanek, B. Leszczyński, P. Moskal, E. Stępień
abstract
Background Lugol's solution is well known for its unique contrasting properties to biological samples in in microcomputed tomography imaging. On the other hand, iron oxide nanoparticles (IONPs), which have much lower attenuation capabilities to X-ray radiation show decent cell penetration and accumulation properties, are increasingly being used as quantitative contrast agents in biology and medicine. In our research, they were used to stain 3D cell structures called spheroids. Aim In this study, the micro computed tomography (microCT) technique was used to visualize and compare the uptake and accumulation of two contrast agents, Lugol's solution and iron (II, III) oxide nanoparticles (IONPs) in the in vitro human spheroid tumour model. Methods The metastatic human melanoma cell line WM266-4 was cultured, first under standard 2D conditions, and after reaching 90% confluence cells was seeded in a low adhesive plate, which allows spheroid formation. On the 7th day of growth, the spheroids were transferred to the tubes and stained with IONPs or Lugol's solution and subjected to microCT imaging. Results Our research allows visualization of the regions of absorption at the level of single cells, with relatively short incubation times - 24h - for Lugol's solution. IONPs proved to be useful only in high concentrations (1 mg/ml) and long incubation times (96h). Conclusions When comparing the reconstructed visualizations of the distribution of these stating agents, it is worth noting that Lugol's solution spreads evenly throughout the spheroids, whereas IONPs (regardless of their size 5 and 30 nm) accumulate only in the outer layer of the spheroid structure.
Combined BNCT and PET for theranostics
M. Silarski, K. Dziedzic-Kocurek, M. Szczepanek
abstract
This short review summarizes the issue of boron distribution monitoring in boron neutron capture therapy (BNCT), which remains a serious drawback of this powerful oncological treatment. Here we present the monitoring methods that are presently used with particular emphasis on positron emission tomography (PET) which has the highest potential to be used for the real-time monitoring of boron biodistribution. We discuss the possibility of using present PET scanners to determine the boron uptake in vivo before the BNCT treatment with the use of p-boronphenylalanine (BPA) labeled with 18F isotope. Several examples of preclinical studies and
clinical trials performed with the use of [18F]FBPA are shown. We also discuss shortly the perspectives of using other radiotracers and boron carriers which may significantly improve the boron imaging with the use of the state-of-the-art Total-Body PET scanners providing a theranostic approach in the BNCT.
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.
Studies of the ortho-Positronium lifetime for cancer diagnostics
Z. Bura, K. Dulski, E. Kubicz, P. Małczak, M. Pędziwiatr, M. Szczepanek, E.Ł. Stępień, P. Moskal
abstract
Positron Annihilation Lifetime Spectroscopy (PALS) is a technique based on the analysis of the lifetime of positronium emitted from implanted or delivered positronium donors. This technique employs the lifetime and intensity dependence on the structure of analyzed material. Due to this specific features, PALS might be used in further research protocols and clinical studies for cancer diagnostic purposes. This article reports the progress in the study design, main objectives of the study, protocols of measurement sand data analysis and further perspective of this study. The main goal of this work was to show the effectiveness of this method and progress in its development. For this purpose, colorectal cancer was examined.
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.
From tests of discrete symmetries to medical imaging with J-PET detector
P. Moskal, J. Baran, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, J. Gajewski, A. Gajos, M. Gorgol, B.C. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, K. Klimaszewski, P. Konieczka, G. Korcyl, T. Kozik, N. Krawczyk, W. Krzemień, E. Kubicz, D. Kumar, S. Niedźwiecki, D. Panek, S. Parzych, E. Perez del Rio, 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
published in: PoS PANIC2021 (2022) 033
We present results on CPT symmetry tests in decays of positronium performed with the precision at the level of 10?4, and positronium images determined with the prototype of the J-PET tomograph. The first full-scale prototype apparatus consists of 192 plastic scintillator strips readout from both ends with vacuum tube photomultipliers. Signals produced by photomultipliers are probed in the amplitude domain and are digitized by FPGA-based readout boards in triggerless mode. In this contribution we report on the first two- and three-photon positronium images and tests of CPT symmetry in positronium decays.
Characterization of spheroid growth based on a new dynamical model
K. Dulski, M. Szczepanek
4th Jagiellonian Symposium on Advances in Particle Physics and Medicine, Cracow, Poland, July 2022
Gold nanoparticles as contrast agents for micro CT imaging
D. Panek, M. Szczepanek, B. Leszczyński, P. Moskal, E. Stępień
4th Jagiellonian Symposium on Advances in Particle Physics and Medicine, Kraków, Poland, July 2022
Spheroids for the study of nanoparticles as contrast agents for CT
D. Panek, M. Szczepanek, B. Leszczyński, P. Moskal, E. Stępień
NanoTech Poland Conference, Poznań, Poland, June 2022
