Single-time-point dosimetry using model selection and the Bayesian fitting method: A proof of concept.

Purpose: This study aimed to determine the effect of model selection on simplified dosimetry for the kidneys using Bayesian fitting (BF) and single-time-point (STP) imaging.

Methods: Kidney biokinetics data of [Lu]Lu-PSMA-617 from mHSPC were collected using SPECT/CT after injection of (3.1 ± 0.

Few-time-points time-integrated activity coefficients calculation using non-linear mixed-effects modeling: Proof of concept for [In]In-DOTA-TATE in kidneys.

Purpose: The purpose of this study is to investigate the accuracy of few-time-points (FTP) time-integrated activity coefficients (TIACs) in peptide-receptor radionuclide therapy (PRRT) using non-linear mixed-effects (NLME) modeling.

Methods: Biokinetic data of [In]In-DOTA-TATE in kidneys at T-1 = (2.9 ± 0.

From Phantoms to Patients: Improved Fusion and Voxel-Wise Analysis of Diffusion-Weighted Imaging and FDG-Positron Emission Tomography in Positron Emission Tomography/Magnetic Resonance Imaging for Combined Metabolic-Diffusivity Index (cDMI).

Hybrid positron emission tomography/magnetic resonance imaging (PET/MR) opens new possibilities in multimodal multiparametric (m2p) image analyses. But even the simultaneous acquisition of positron emission tomography (PET) and magnetic resonance imaging (MRI) does not guarantee perfect voxel-by-voxel co-registration due to organs and distortions, especially in diffusion-weighted imaging (DWI), which would be, however, crucial to derive biologically meaningful information. Thus, our aim was to optimize fusion and voxel-wise analyses of DWI and standardized uptake values (SUVs) using a novel software for m2p analyses.

Exploratory Tau PET/CT with [11C]PBB3 in Patients with Suspected Alzheimer's Disease and Frontotemporal Lobar Degeneration: A Pilot Study on Correlation with PET Imaging and Cerebrospinal Fluid Biomarkers.

Accurately diagnosing Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) is challenging due to overlapping symptoms and limitations of current imaging methods. This study investigates the use of [11C]PBB3 PET/CT imaging to visualize tau pathology and improve diagnostic accuracy. Given diagnostic challenges with symptoms and conventional imaging, [11C]PBB3 PET/CT's potential to enhance accuracy was investigated by correlating tau pathology with cerebrospinal fluid (CSF) biomarkers, positron emission tomography (PET), computed tomography (CT), amyloid-beta, and Mini-Mental State Examination (MMSE).

Single-Time-Point Renal Dosimetry Using Nonlinear Mixed-Effects Modeling and Population-Based Model Selection in [Lu]Lu-PSMA-617 Therapy.

The aim of this study was to investigate the accuracy of single-time-point (STP) renal dosimetry imaging using SPECT/CT data, a nonlinear mixed-effects (NLME) model, and a population-based model selection (PBMS) in a large population for Lu-labeled prostate-specific membrane antigen therapy. Biokinetic data (mean ± SD) of [Lu]Lu-PSMA-617 in kidneys at time points 1 (1.8 ± 0.

A PBPK model for PRRT with [Lu]Lu-DOTA-TATE: Comparison of model implementations in SAAM II and MATLAB/SimBiology.

Unlabelled: Physiologically based pharmacokinetic (PBPK) models offer the ability to simulate and predict the biodistribution of radiopharmaceuticals and have the potential to enable individualised treatment planning in molecular radiotherapy. The objective of this study was to develop and implement a whole-body compartmental PBPK model for peptide receptor radionuclide therapy (PRRT) with [Lu]Lu-DOTA-TATE in SimBiology to allow for more complex analyses. The correctness of the model implementation was ensured by comparing its outputs, such as the time-integrated activity (TIA), with those of a PBPK model implemented in SAAM II software.

Time-Activity data fitting in molecular Radiotherapy: Methodology and pitfalls.

Absorbed radiation doses are essential in assessing the effects, e.g. safety and efficacy, of radiopharmaceutical therapy (RPT).

Combined morphologic-metabolic biomarkers from [18F]FDG-PET/CT stratify prognostic groups in low-risk NSCLC.

Aim: The aim of this study was to derive prognostic parameters from 2-[F]fluoro-2-deoxy-D-glucose ([F]FDG-PET/CT) in patients with low-risk NSCLC and determine their prognostic value.

Methods: 81 (21 female, mean age 66 a) therapy-naive patients that underwent [18F]FDG-PET/CT before histologic confirmation of NSCLC with stadium I and II between 2008-2016 were included. A mean follow-up time of 58 months (13-176), overall and progression free survival (OS, PFS) were registered.

Optimization of Radiolabeling of a [Y]Y-Anti-CD66-Antibody for Radioimmunotherapy before Allogeneic Hematopoietic Cell Transplantation.

For patients with acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia, allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. In addition to standard conditioning regimens for HCT, high-dose radioimmunotherapy (RIT) offers the unique opportunity to selectively deliver a high dose of radiation to the bone marrow while limiting side effects. Modification of a CD66b-specific monoclonal antibody (mAb) with a DTPA-based chelating agent should improve the absorbed dose distribution during therapy.

Population-based model selection for an accurate estimation of time-integrated activity using non-linear mixed-effects modelling.

Purpose: Personalized treatment planning in Molecular Radiotherapy (MRT) with accurately determining the absorbed dose is highly desirable. The absorbed dose is calculated based on the Time-Integrated Activity (TIA) and the dose conversion factor. A crucial unresolved issue in MRT dosimetry is which fit function to use for the TIA calculation.

Single-time-point dosimetry using model selection and nonlinear mixed-effects modelling: a proof of concept.

Purpose: This project aims to develop and evaluate a method for accurately determining time-integrated activities (TIAs) in single-time-point (STP) dosimetry for molecular radiotherapy. It performs a model selection (MS) within the framework of the nonlinear mixed-effects (NLME) model (MS-NLME).

Methods: Biokinetic data of [In]In-DOTATATE activity in kidneys at T1 = (2.

Organ absorbed doses in the IORT treatment of breast cancer with the INTRABEAM device: a Monte-Carlo study.

: The current prescription and the assessment of the delivered absorbed dose in intraoperative radiation therapy (IORT) with the INTRABEAM system rely mainly on depth-dose measurements in water. The accuracy of this approach is limited because tissue heterogeneity is ignored. It is also difficult to accurately determine the dose delivered to the patient experimentally as the steep dose gradient is highly sensitive to geometric errors.

Preclinical PET and MR Evaluation of Zr- and Ga-Labeled Nanodiamonds in Mice over Different Time Scales.

Nanodiamonds (NDs) have high potential as a drug carrier and in combination with nitrogen vacancies (NV centers) for highly sensitive MR-imaging after hyperpolarization. However, little remains known about their physiological properties in vivo. PET imaging allows further evaluation due to its quantitative properties and high sensitivity.

Blocking Studies to Evaluate Receptor-Specific Radioligand Binding in the CAM Model by PET and MR Imaging.

Inhibition studies in small animals are the standard for evaluating the specificity of newly developed drugs, including radiopharmaceuticals. Recently, it has been reported that the tumor accumulation of radiotracers can be assessed in the chorioallantoic membrane (CAM) model with similar results to experiments in mice, such contributing to the 3Rs principles (reduction, replacement, and refinement). However, inhibition studies to prove receptor-specific binding have not yet been performed in the CAM model.

Single-time-point estimation of absorbed doses in PRRT using a non-linear mixed-effects model.

Introduction: Estimation of accurate time-integrated activity coefficients (TIACs) and radiation absorbed doses (ADs) is desirable for treatment planning in peptide-receptor radionuclide therapy (PRRT). This study aimed to investigate the accuracy of a simplified dosimetry using a physiologically-based pharmacokinetic (PBPK) model, a nonlinear mixed effect (NLME) model, and single-time-point imaging to calculate the TIACs and ADs of Y-DOTATATE in various organs of dosimetric interest and tumors.

Materials & Methods: Biokinetic data of In-DOTATATE in tumors, kidneys, liver, spleen, and whole body were obtained from eight patients using planar scintigraphic imaging at T1 = (2.

Quantitative analysis of regional distribution of tau pathology with 11C-PBB3-PET in a clinical setting.

Purpose: The recent developments of tau-positron emission tomography (tau-PET) enable in vivo assessment of neuropathological tau aggregates. Among the tau-specific tracers, the application of 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) in PET shows high sensitivity to Alzheimer disease (AD)-related tau deposition. The current study investigates the regional tau load in patients within the AD continuum, biomarker-negative individuals (BN) and patients with suspected non-AD pathophysiology (SNAP) using 11C-PBB3-PET.

A Physiologically Based Pharmacokinetic Model for In Vivo Alpha Particle Generators Targeting Neuroendocrine Tumors in Mice.

In vivo alpha particle generators have great potential for the treatment of neuroendocrine tumors in alpha-emitter-based peptide receptor radionuclide therapy (α-PRRT). Quantitative pharmacokinetic analyses of the in vivo alpha particle generator and its radioactive decay products are required to address concerns about the efficacy and safety of α-PRRT. A murine whole-body physiologically based pharmacokinetic (PBPK) model was developed for Pb-labeled somatostatin analogs (Pb-SSTA).

A population-based method to determine the time-integrated activity in molecular radiotherapy.

Background: The calculation of time-integrated activities (TIAs) for tumours and organs is required for dosimetry in molecular radiotherapy. The accuracy of the calculated TIAs is highly dependent on the chosen fit function. Selection of an adequate function is therefore of high importance.

Comparison of Quantification of Target-Specific Accumulation of [F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI.

Assessment of biodistribution and specific tumor accumulation is essential for the development of new radiopharmaceuticals and requires animal experiments. The HET-CAM (hens-egg test-chorioallantoic membrane) model can be used in combination with the non-invasive imaging modalities PET and MRI for pre-selection during radiopharmaceutical development to reduce the number of animal experiments required. Critical to the acceptance of this model is the demonstration of the quantifiability and reproducibility of these data compared to the standard animal model.

A Whole-Body Physiologically Based Pharmacokinetic Model for Alpha Particle Emitting Bismuth in Rats.

α particle emitting bismuth (Bi) as decay product of Pb-labeled pharmaceuticals has been effective in targeted α particle therapy (TAT). Estimating the contribution of Bi released from its chelator to the absorbed doses in nontarget tissues is challenging in TAT. Physiologically based pharmacokinetic (PBPK) modeling can help overcome this limitation.

EANM position paper on the role of radiobiology in nuclear medicine.

With an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored.

Mathematical Modeling of Alpha Particle Generators and Chelator Stability.

Targeted α particle therapy using long-lived α particle generators is cytotoxic to target tissues. However, the redistribution of released radioactive daughters through the circulation should be considered. A mathematical model was developed to describe the physicochemical kinetics of Pb-labeled pharmaceuticals and its radioactive daughters.