Distribution Of Radiopharmaceuticals Research Articles

Mathematical modeling of 18F-Fluoromisonidazole (18F-FMISO) radiopharmaceutical transport in vascularized solid tumors

18F-Fluoromisonidazole (18F-FMISO) is a highly promising positron emission tomography radiopharmaceutical for identifying hypoxic regions in solid tumors. This research employs spatiotemporal multi-scale mathematical modeling to explore how different levels of angiogenesis influence the transport of radiopharmaceuticals within tumors. In this study, two tumor geometries with heterogeneous and uniform distributions of capillary networks were employed to incorporate varying degrees of microvascular density. The synthetic image of the heterogeneous and vascularized tumor was generated by simulating the angiogenesis process. The proposed multi-scale spatiotemporal model accounts for intricate physiological and biochemical factors within the tumor microenvironment, such as the transvascular transport of the radiopharmaceutical agent, its movement into the interstitial space by diffusion and convection mechanisms, and ultimately its uptake by tumor cells. Results showed that both quantitative and semi-quantitative metrics of 18F-FMISO uptake differ spatially and temporally at different stages during tumor growth. The presence of a high microvascular density in uniformly vascularized tumor increases cellular uptake, as it allows for more efficient release and rapid distribution of radiopharmaceutical molecules. This results in enhanced uptake compared to the heterogeneous vascularized tumor. In both heterogeneous and uniform distribution of microvessels in tumors, the diffusion transport mechanism has a more pronounced than convection. The findings of this study shed light on the transport phenomena behind 18F-FMISO radiopharmaceutical distribution and its delivery in the tumor microenvironment, aiding oncologists in their routine decision-making processes.

Radiopharmaceuticals Targeting Gastrin-Releasing Peptide Receptor for Diagnosis and Therapy of Prostate Cancer.

The high incidence and heavy disease burden of prostate cancer (PC) require accurate and comprehensive assessment for appropriate disease management. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) cannot detect PSMA-negative lesions, despite its key role in PC disease management. The overexpression of gastrin-releasing peptide receptor (GRPR) in PC lesions reportedly performs as a complementary target for the diagnosis and therapy of PC. Radiopharmaceuticals derived from the natural ligands of GRPR have been developed. These radiopharmaceuticals enable the visualization and quantification of GRPR within the body, which can be used for disease assessment and therapeutic guidance. Recently developed radiopharmaceuticals exhibit improved pharmacokinetic parameters without deterioration in affinity. Several heterodimers targeting GRPR have been constructed as alternatives because of their potential to detect tumor lesions with a low diagnostic efficiency of single target detection. Moreover, some GRPR-targeted radiopharmaceuticals have entered clinical trials for the initial staging or biochemical recurrence detection of PC to guide disease stratification and therapy, indicating considerable potential in PC disease management. Herein, we comprehensively summarize the progress of radiopharmaceuticals targeting GRPR. In particular, we discuss the impact of ligands, chelators, and linkers on the distribution of radiopharmaceuticals. Furthermore, we summarize a potential design scheme to facilitate the advancement of radiopharmaceuticals and, thus, prompt clinical translation.

Radiopharmaceutical transport in solid tumors via a 3-dimensional image-based spatiotemporal model

Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA)-targeted radiopharmaceutical therapy is a clinically approved treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Even though common practice reluctantly follows “one size fits all” approach, medical community believes there is significant room for deeper understanding and personalization of radiopharmaceutical therapies. To pursue this aim, we present a 3-dimensional spatiotemporal radiopharmaceutical delivery model based on clinical imaging data to simulate pharmacokinetic of 177Lu-PSMA within the prostate tumors. The model includes interstitial flow, radiopharmaceutical transport in tissues, receptor cycles, association/dissociation with ligands, synthesis of PSMA receptors, receptor recycling, internalization of radiopharmaceuticals, and degradation of receptors and drugs. The model was studied for a range of values for injection amount (100–1000 nmol), receptor density (10–500 nmol•l–1), and recycling rate of receptors (10–4 to 10–1 min–1). Furthermore, injection type, different convection-diffusion-reaction mechanisms, characteristic time scales, and length scales are discussed. The study found that increasing receptor density, ligand amount, and labeled ligands improved radiopharmaceutical uptake in the tumor. A high receptor recycling rate (0.1 min–1) increased radiopharmaceutical concentration by promoting repeated binding to tumor cell receptors. Continuous infusion results in higher radiopharmaceutical concentrations within tumors compared to bolus administration. These insights are crucial for advancing targeted therapy for prostate cancer by understanding the mechanism of radiopharmaceutical distribution in tumors. Furthermore, measures of characteristic length and advection time scale were computed. The presented spatiotemporal tumor transport model can analyze different physiological parameters affecting 177Lu-PSMA delivery.

Assessment of arterial blood flow in the microvasculature of the lower extremities in patients with chronic ischemia using a single-photon emission computed tomography (SPECT)

Introduction. Obliterating atherosclerosis of the lower extremity vessels is a chronic, steadily progressive disease of the leg arteries, with a high risk of limb amputation and death. Timely diagnosis and adequate treatment will help slow the disease progression, maintain the patient’s good health for a long time and avoid complications. Purpose. To study arterial blood flow in the microvasculature of the lower extremities, to qualitatively and quantitatively assess perfusion disturbances in functionally significant muscles of the lower extremities. Material and methods. Radionuclide examination of the main vessels and microvasculature of the lower extremities was performed in 36 patients, five of them with a diagnosis of lower extremity obliterating atherosclerosis in dynamics. Radiopharmaceuticals was administered through a catheter installed endovascularly above the aortic bifurcation when patients underwent arteriography of the lower extremity vessels, which also involves intra-arterial administration of a radiopaque contrast agent. Results. When processing the radiological study results, we visually assessed the distribution of radiopharmaceuticals in the vascular bed of the lower extremities, identified the asymmetry in the accumulation of radiopharmaceuticals as a percentage, quantified the accumulation of radiopharmaceutical pulses in the projection of the pelvic, thigh, leg and foot muscles, determining the level of accumulation in each of the areas of interest as a percentage. The radiological study results and direct aortic arteriography of the lower extremities with determination of the level of arterial stenosis confirmed the ischemic nature of the pain syndrome; and in the control study, the effectiveness of treatment with an improvement in perfusion parameters. Conclusions. Intra-arterial administration of radiopharmaceuticals makes it possible to assess the condition of the peripheral arterial bed, which has a significant role in the prognosis of lower extremity atherosclerosis and the results of reconstructive interventions. The method makes possible a hybrid topometric comparison of arterio-perfusion maps for diagnosis, planned treatment and monitoring of its results in dynamics.

Localized radiotherapy of solid tumors using radiopharmaceutical loaded implantable system: insights from a mathematical model.

Computational models yield valuable insights into biological interactions not fully elucidated by experimental approaches. This study investigates an innovative spatiotemporal model for simulating the controlled release and dispersion of radiopharmaceutical therapy (RPT) using 177Lu-PSMA, a prostate-specific membrane antigen (PSMA) targeted radiopharmaceutical, within solid tumors via a dual-release implantable delivery system. Local delivery of anticancer agents presents a strategic approach to mitigate adverse effects while optimizing therapeutic outcomes. This study evaluates various factors impacting RPT efficacy, including hypoxia region extension, binding affinity, and initial drug dosage, employing a novel 3-dimensional computational model. Analysis gauges the influence of these factors on radiopharmaceutical agent concentration within the tumor microenvironment. Furthermore, spatial and temporal radiopharmaceutical distribution within both the tumor and surrounding tissue is explored. Analysis indicates a significantly higher total concentration area under the curve within the tumor region compared to surrounding normal tissue. Moreover, drug distribution exhibits notably superior efficacy compared to the radiation source. Additionally, low microvascular density in extended hypoxia regions enhances drug availability, facilitating improved binding to PSMA receptors and enhancing therapeutic effectiveness. Reductions in the dissociation constant (KD) lead to heightened binding affinity and increased internalized drug concentration. Evaluation of initial radioactivities (7.1×107, 7.1×108, and 7.1×109 [Bq]) indicates that an activity of 7.1×108 [Bq] offers a favorable balance between tumor cell elimination and minimal impact on normal tissues. These findings underscore the potential of localized radiopharmaceutical delivery strategies and emphasize the crucial role of released drugs relative to the radiation source (implant) in effective tumor treatment. Decreasing the proximity of the drug to the microvascular network and enhancing its distribution within the tumor promote a more effective therapeutic outcome. The study furnishes valuable insights for future experimental investigations and clinical trials, aiming to refine medication protocols and minimize reliance on in vivo testing.

44Sc production from enriched 47TiO2 targets with a medical cyclotron

44Sc is a β+-emitter which has been extensively studied for nuclear medicine applications. Its promising decay characteristics [t1/2 = 3.97 h, Eβ+ = 632 keV (94.3%), Eγ = 1157 keV (99.9%); 1499 keV (0.91%)] make it highly attractive for clinical PET imaging, offering an alternative to the widely used 68Ga [t1/2 = 67.7 min, Eβ+ = 836 keV (87.7%)]. Notably, its nearly fourfold longer half-life opens avenues for applications with biomolecules having extended biological half-lives and enables the centralized distribution of 44Sc radiopharmaceuticals. An additional advantage of employing 44Sc as a diagnostic radioisotope lies in its counterpart, the β−-emitter 47Sc, which is currently under investigation for targeted radiotherapy. Together, they form an ideal theranostic pair, providing a comprehensive solution for both diagnostic imaging and therapeutic applications in nuclear medicine.At the Bern medical cyclotron, a study to optimize the production of scandium radioisotopes is currently ongoing. In this context, proton irradiation of titanium targets has been investigated, exploiting the reactions 47Ti(p,α)44Sc and 50Ti(p,α)47Sc. This approach enables the production of Sc radioisotopes within a single PET medical cyclotron facility, employing identical chemical procedures for target preparation and post-irradiation processing.In this paper, we report on cross-section measurements of the 47Ti(p,α)44Sc nuclear reaction using 95.7% enriched 47TiO2 targets. On the basis of the obtained results, the production yield and purity were calculated to assess the optimal irradiation conditions. Production tests were performed to confirm these findings.

A Review of Hypoxia Imaging Using 18F-Fluoromisonidazole Positron Emission Tomography.

Tumor hypoxia is an essential factor related to malignancy, prognosis, and resistance to treatment. Positron emission tomography (PET) is a modality that visualizes the distribution of radiopharmaceuticals administered into the body. PET imaging with [18F]fluoromisonidazole ([18F]FMISO) identifies hypoxic tissues. Unlike [18F]fluorodeoxyglucose ([18F]FDG)-PET, fasting is not necessary for [18F]FMISO-PET, but the waiting time from injection to image acquisition needs to be relatively long (e.g., 2-4h). [18F]FMISO-PET images can be displayed on an ordinary commercial viewer on a personal computer (PC). While visual assessment is fundamental, various quantitative indices such as tumor-to-muscle ratio have also been proposed. Several novel hypoxia tracers have been invented to compensate for the limitations of [18F]FMISO.

Beyond Average: α-Particle Distribution and Dose Heterogeneity in Bone Metastatic Prostate Cancer.

α-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the α-particle pathlength. We sought to determine the distribution of clinically approved [223Ra]RaCl2 in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. 223Ra activity in each sample was recorded, and the microstructure of biopsy specimens was analyzed by micro-CT. Quantitative autoradiography and histopathology were segmented and registered with an automated procedure. Activity distributions by tissue compartment and dosimetry calculations based on the MIRD formalism were performed. Results: We revealed the activity distribution differences across and within patient samples at the macro- and microscopic scales. Microdistribution analysis confirmed localized high-activity regions in a background of low-activity tissue. We evaluated heterogeneous α-particle emission distribution concentrated at bone-tissue interfaces and calculated spatially nonuniform absorbed-dose profiles. Conclusion: Primary patient data of radiopharmaceutical therapy distribution at the small scale revealed that 223Ra uptake is nonuniform. Dose estimates present both opportunities and challenges to enhance patient outcomes and are a first step toward personalized treatment approaches and improved understanding of α-particle radiopharmaceutical therapies.

Optimization of radioprotective dose of Juglans nigra leaf extract using response surface methodology

J. nigra leaf contains mixture of various pharmacologically active compounds and it is assumed that they may have the potential radioprotective effect. The purpose of this work was to predict radioprotective doses by correlating changes in organ distribution of radiopharmaceuticals with extract dose levels and rat body weight using response surface methodology (RSM) based on a second-order polynomial equation. The extract was administered daily by oral gavage to rats at dose of 6.9, 10.3, or 13.7 mg kg−1 body weight (bw) day−1 for 10 days. On the eleventh day, 0.1 ml of the one radiopharmaceutical (Na99mTcO4, 99mTc-dimercaptosuccinic acid and 99mTc-tin colloid) was injected into the tail vein. The statistical parameters: the coefficient of determination (0.81–0.95), the coefficient of variation (3.05–11.1), the adequate precision (8.82–19.12) and the mean relative percentage deviation (± 2.3–8.2) were indicated the precision and reliability of RSM. Using RSM, the predicted daily dose of leaf extract ranging from 11.19 to 11.99 mg kg−1 bw may be considered as an optimal daily radiopotective dose for protection of organs from radiation in cases of planned radiation exposures.

Deep Learning-Based Delayed PET Image Synthesis from Corresponding Early Scanned PET for Dosimetry Uptake Estimation.

The acquisition of in vivo radiopharmaceutical distribution through imaging is time-consuming due to dosimetry, which requires the subject to be scanned at several time points post-injection. This study aimed to generate delayed positron emission tomography images from early images using a deep-learning-based image generation model to mitigate the time cost and inconvenience. Eighteen healthy participants were recruited and injected with [18F]Fluorodeoxyglucose. A paired image-to-image translation model, based on a generative adversarial network (GAN), was used as the generation model. The standardized uptake value (SUV) mean of the generated image of each organ was compared with that of the ground-truth. The least square GAN and perceptual loss combinations displayed the best performance. As the uptake time of the early image became closer to that of the ground-truth image, the translation performance improved. The SUV mean values of the nominated organs were estimated reasonably accurately for the muscle, heart, liver, and spleen. The results demonstrate that the image-to-image translation deep learning model is applicable for the generation of a functional image from another functional image acquired from normal subjects, including predictions of organ-wise activity for specific normal organs.

Atypical Uptake of 18<sup>F</sup>DG in White Adipose Tissue During PET/CT in Children

Positron emission tomography combined with computed tomography (PET/CT) with 18F-fluoro-deoxyglucose (18F-FDG) plays an important role in the management of cancer patients and is mainly used for primary staging, evaluation of treatment response and detection of disease recurrence. Due to non-specific nature of 18F-FDG uptake, a radiologist must be familiar with both physiological and atypical distribution of radiopharmaceuticals. Inappropriate patient preparation for the study and/or taking certain drugs can lead to abnormal 18F-FDG distribution. Our clinical case demonstrates an atypical uptake of 18F-FDG in white adipose tissue in a child treated with glucocorticoids for a long time.

Partie 3. Aspects structurels spécifiques du service de médecine nucléaire

A nuclear medicine department is made up of several sectors whose layout, governed by the level of exposure to radiation (“cold” or “hot” sectors), must necessarily take into account the constraints of preparation and distribution of radiopharmaceuticals, storage/management of contaminated waste and effluent, and the patient pathway (reception, MRP injection, image acquisition. ASN Guide No. 32 specifically specifies the rules for the design and operation of nuclear medicine departments. Without forgetting that the ASN is not the only body with requirements concerning the structuring of a service, it is sometimes complex to modulate the premises in an optimal way with all the difficulties and architectural specificities that this can cause. anticipated RIV, through its impact on the layout of the service, is a structural issue in the short/medium term.

A Review on Tumor Control Probability (TCP) and Preclinical Dosimetry in Targeted Radionuclide Therapy (TRT).

Targeted radionuclide therapy (TRT) uses radiopharmaceuticals to specifically irradiate tumor cells while sparing healthy tissue. Response to this treatment highly depends on the absorbed dose. Tumor control probability (TCP) models aim to predict the tumor response based on the absorbed dose by taking into account the different characteristics of TRT. For instance, TRT employs radiation with a high linear energy transfer (LET), which results in an increased effectiveness. Furthermore, a heterogeneous radiopharmaceutical distribution could result in a heterogeneous dose distribution at a tissue, cellular as well as subcellular level, which will generally reduce the tumor response. Finally, the dose rate in TRT is protracted, relatively low, and variable over time. This allows cells to repair more DNA damage, which may reduce the effectiveness of TRT. Within this review, an overview is given on how these characteristics can be included in TCP models, while some experimental findings are also discussed. Many parameters in TCP models are preclinically determined and TCP models also play a role in the preclinical stage of radiopharmaceutical development; however, this all depends critically on the calculated absorbed dose. Accordingly, an overview of the existing preclinical dosimetry methods is given, together with their limitation and applications. It can be concluded that although the theoretical extension of TCP models from external beam radiotherapy towards TRT has been established quite well, the experimental confirmation is lacking. Thus, requiring additional comprehensive studies at the sub-cellular, cellular, and organ level, which should be provided with accurate preclinical dosimetry.

Radiation exposure to extremities in medical applications and its implications for the radiation protection of workers in the Philippines

In medical applications, non-homogeneous radiation exposure conditions may be encountered and whole-body monitoring alone may not be an adequate assessment of doses received by workers. This paper investigated the exposure to extremities in medical applications in the Philippines in terms of personal dose equivalent Hp(0.07). Profiles of monitored workers, dose levels, implications on optimization of occupational exposures, and factors affecting the extremity monitoring implementation were studied. The results show that <3% of workers are monitored for extremities, and there is no monitoring of eye lens dose. There is no extremity monitoring in diagnostic radiology, particularly interventional radiology. Dose levels to extremities were higher and more varied than whole-body doses. In nuclear medicine, the median annual extremity dose is 1.2 mSv, the interquartile range (IQR) is 7.6 mSv (Q1 = 0.5 mSv, Q3 = 8.1 mSv), and the maximum dose is 35 mSv. These median and IQR dose values are four and eight times higher, respectively, compared to the whole-body dose. In radiopharmaceutical distribution, the extremity median annual dose is five times higher than the whole-body dose, and the IQR value is 12 times higher where IQR is 12.1 mSv (Q1 = 0.1 mSv, Q3 = 12.2 mSv). Most notable is in cyclotron operations where <40% of workers were monitored on their extremities; however, the median dose is 100 times higher than the whole-body dose, with a maximum dose of 148 mSv. The results imply that there may be an underassessment of occupational exposure of workers in medical applications. As monitoring results are used for the establishment of a radiation protection program, lack of consideration of extremity doses can lead to inadequate measures in the optimization of worker protection. This study thus shows the need to enhance the implementation of extremity and eye lens dose monitoring in the Philippines to further strengthen the radiation protection of workers in medical applications.

Spatiotemporal multi-scale modeling of radiopharmaceutical distributions in vascularized solid tumors

We present comprehensive mathematical modeling of radiopharmaceutical spatiotemporal distributions within vascularized solid tumors. The novelty of the presented model is at mathematical level. From the mathematical viewpoint, we provide a general modeling framework for the process of radiopharmaceutical distribution in the tumor microenvironment to enable an analysis of the effect of various tumor-related parameters on the distribution of different radiopharmaceuticals. We argue that partial differential equations (PDEs), beyond conventional methods, including ODE-based kinetic compartment modeling, can be used to evaluate radiopharmaceutical distribution in both time and space. In addition, we consider the spatially-variable dynamic structure of tumor microvascular networks to simulate blood flow distribution. To examine the robustness of the model, the effects of microvessel density (MVD) and tumor size, as two important factors in tumor prognosis, on the radiopharmaceutical distribution within the tumor are investigated over time (in the present work, we focus on the radiopharmaceutical [18F]FDG, yet the framework is broadly applicable to radiopharmaceuticals). Results demonstrate that the maximum total uptake of [18F]FDG at all time frames occurs in the tumor area due to the high capillary permeability and lack of a functional lymphatic system. As the MVD of networks increases, the mean total uptake in the tumor is also enhanced, where the rate of diffusion from vessel to tissue has the highest contribution and the rate of convection transport has the lowest contribution. The results of this study can be used to better investigate various phenomena and bridge a gap among cancer biology, mathematical oncology, medical physics, and radiology.

Predicting response of micrometastases with MIRDcell V3: proof of principle with 225Ac-DOTA encapsulating liposomes that produce different activity distributions in tumor spheroids.

The spatial distribution of radiopharmaceuticals within multicellular clusters is known to have a significant effect on their biological response. Most therapeutic radiopharmaceuticals distribute nonuniformly in tissues which makes predicting responses of micrometastases challenging. The work presented here analyzes published temporally dependent nonuniform activity distributions within tumor spheroids treated with actinium-225-DOTA encapsulating liposomes (225Ac-liposomes) and uses these data in MIRDcellV3.11 to calculate absorbed dose distributions and predict biological response. The predicted responses are compared with experimental responses. Four types of liposomes were prepared having membranes with different combinations of release (R) and adhesion (A) properties. The combinations were R-A-, R-A+, R+A-, and R+A+. These afford different penetrating properties into tissue. The liposomes were loaded with either carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) or 225Ac. MDA-MB-231 spheroids were treated with the CFDA-SE-liposomes, harvested at different times, and the time-integrated CFDA-SE concentration at each radial position within the spheroid was determined. This was translated into mean 225Ac decays/cell versus radial position, uploaded to MIRDcell, and the surviving fraction of cells in spherical multicellular clusters was simulated. The MIRDcell-predicted surviving fractions were compared with experimental fractional-outgrowths of the spheroids following treatment with 225Ac-liposomes. The biological responses of the multicellular clusters treated with 225Ac-liposomes with physicochemical properties R+A+, R-A+, and R-A- were predicted by MIRDcell with statistically significant accuracy. The prediction for R+A- was not predicted accurately. In most instances, MIRDcell predicts responses of spheroids treated with 225Ac-liposomes that result in different tissue-penetrating profiles of the delivered radionuclides.

Possibilities of brain SPECT with perfusion radiopharmaceuticals for the quantitative assessment of cognitive changes in patients with hypertensive encephalopathy

Background. Vascular diseases of the brain, which lead to encephalopathy, are a significant medical and social problem. The main clinical tool for diagnosing cognitive impairments is a neuropsychological testing. Its disadvantages are a big number of different tests, which are used in clinical institutions, and thus, make it extremely complicated to compare the data; in monitoring studies, patients can learn answers, which somewhat distorts the results; there is also a possibility of a non-objective doctor’s impact on the results of the conducted test. Therefore, the development of methods for assessing the neuropsychological and cognitive state of patients based on objective data is an urgent task. Besides, to this date, it is not completely known which segments of the brain directly or indirectly affect this or that cognitive function. Purpose – to develop a methodology for assessing the scores of neuropsychological testing (NPT) in patients with atherosclerotic hypertensive encephalopathy (ATHE) based on data from single-photon emission computed tomography (SPECT) with perfusion radiopharmaceuticals (RPh). Materials and Methods. NPT and SPECT data of twenty patients with clinical diagnosis of atherosclerotic hypertensive encephalopathy were analyzed. The principal scales used during the study were the following: Montgomery – Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HARS), Schulte Table, O. Luria. Tomographic images of the brain were obtained on the gamma camera «E. Cam» (Siemens) using perfusion lipophilic radiopharmaceutical 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO). Processing and analysis of the scintigraphic images were conducted in the original software «ScintiBrain», which is implemented in the Matlab-2018 environment. The quantitative characteristics of accumulation and spatial distribution of RPh in the brain were: specific accumulation of RPh (Upt) and parameter of intrahemispheric symmetry (IHS) of perfusion in the brain segments. Based on machine learning method, which can be attributed to regression methods, NPT data were compared with the ratio of Upt and IHS between different segments of the brain Results. As a result of the analysis (machine learning) of 190 Upt and IHS ratios between different segments of the brain with NPT values, the most informative ratios in terms of regression analysis were highlighted. The independence of Upt and IHS makes it possible to increase the accuracy of calculations of NPT values by algebraic averaging of calculations by Upt and IHS ratios.&#x0D; Machine learning results by both Upt and IHS values had one order of correlation and a mean squared error in the tests. The correlation coefficient of linear approximation of values between the SPECT and NPT data was in the range of 0.75–0.93 (p &lt; 0.01), which corresponded to the average relative error in calculations of test values from 7–22%. Conclusions. For the first time, a method of quantitative assessment of the neuropsychological and cognitive state of patients was developed on the basis of an objective research method, namely SPECT. The average relative error in calculations of equivalent values of NPT was in the range of 7 – 22%. At the same time, it was shown that the neuropsychological and cognitive state of patients, in particular patients with ATHE, according to the analysis of effective brain perfusion, didn’t correspond to one specific segment of the brain, but instead to a group of three interrelations of RPh accumulation in the highlighted regions of interest. The presence of a sufficiently high correlation between the NPT data and the indicators of the specific accumulation of RPh and the IHS in the brain segments showed that the neuropsychological and cognitive state of the patient depended not only on the level of accumulation of RPh in segments, but also on its spatial distribution.

Current use and future potential of (physiologically based) pharmacokinetic modelling of radiopharmaceuticals: a review.

Rationale: Physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PK) modelling approaches are widely accepted in non-radiopharmaceutical drug development and research, while there is no major role for these approaches in radiopharmaceutical development yet. In this review, a literature search was performed to specify different research purposes and questions that have previously been answered using both PBPK and population PK modelling for radiopharmaceuticals. Methods: The literature search was performed using the databases PubMed and Embase. Wide search terms included radiopharmaceutical, tracer, radioactivity, physiologically based pharmacokinetic model, PBPK, population pharmacokinetic model and nonlinear mixed-effects model. Results: Eight articles and twenty articles were included for this review based on this literature search for population PK modelling and PBPK modelling, respectively. Included population PK analyses showed to have an added value to develop predictive models for a population and to describe individual variability sources. Main purposes of PBPK models appeared related to optimizing treatment (planning), or more specifically: to find the optimal combination of peptide amount and radioactivity, to optimize treatment planning by reducing the number of measurements, to individualize treatment, to get insights in differences between pre-therapeutic and therapeutic scans or to understand inter-patient differences. Other main research subjects were regarding radiopharmaceutical comparisons, selecting ligands based on their peptide characteristics and gaining a better understanding of drug-drug interactions. Conclusions: The use of PK modelling approaches in radiopharmaceutical research remains scarce, but can be expanded to obtain a better understanding of PK and whole-body distribution of radiopharmaceuticals in general. PK modelling of radiopharmaceuticals has great potential for the nearby future and could contribute to the evolving research of radiopharmaceuticals.

High-resolution phantom of a nephron for radiation nephrotoxicity evaluation in biophysical simulations

&lt;abstract&gt; &lt;p&gt;Computer simulation plays an important role in medical physics. The aim of this study was to generate an accurate model to calculate the absorbed dose at the cell level in a voxelized phantom of nephrons. In order to implement a model of kidney microdosimetry, a 3D mesh phantom of a human kidney nephron, representing a cortical nephron, was digitized to create a 3D voxelized phantom of a nephron for use in Monte Carlo simulations. The phantom was fed to GATE Monte Carlo toolkits, and simulations were performed to calculate the absorbed dose/energy from alpha and electron sources over a range of energy levels. The results were compared to the results published in literature that were derived by using a stylized phantom. The dose estimated in subunits of the voxelized and stylized phantoms showed a considerable bias (average of relative differences). The maximum difference for self-absorption was 12.5%, and up to 20% for cross-absorption. The digital phantom showed very significant differences in dose distribution among the cells in different subunits of the nephron. The results demonstrated that a small dissimilarity in the size and shape of subunits can lead to a considerable difference in the microdosimetry results. The model presented in this study offers a phantom that not only presents the realistic geometry of a nephron, which has been neglected in previous stylized models, but also one that has the capability of plotting the spatial distribution of the absorbed dose for any distribution of radiopharmaceuticals in nephron cells.&lt;/p&gt; &lt;/abstract&gt;

Comparative Study of Various Nuclear Medicine Imaging Technique - A Review

Nuclear Medicine is a medical specialty that allows modern diagnostics and treatments using radiopharmaceuticals original radiotracers (drugs linked to a radioactive isotope). The radiopharmaceuticals are considered a special group of drugs and thus their preparation and use are regulated by a set of policies that have been adopted by individual member countries. The radiopharmaceuticals used in diagnostic examinations are administered in very small doses. So, in general, they have no pharmacological action, side effects or serious adverse reactions. The most serious issue with their use is the potential for diagnostic mistakes due to changes in their biodistribution. The appearance and development of new radiopharmaceuticals in both the diagnostic and therapeutic domains, as well as the impact of new multimodality imaging techniques, are all having a significant impact on nuclear medicine (SPECT-CT, PET-CT, PET-MRI, etc.). It is crucial to understand the techniques limitations, radiopharmaceutical distribution and potential physiological changes, radiological contrast contraindications and bad responses, and the possibility of both interfering. The process of generating radiopharmaceuticals is introduced and relevant interactions of radiation with matter are discussed. Diagnostic nuclear medicine instrumentation is explained, and future trends in nuclear medicine imaging technology are forecasted.