Feasibility of Using F-FDG PET/CT Radiomics and Machine Learning to Detect Drug-Induced Interstitial Lung Disease.

Background: Bleomycin is an oncolytic and antibiotic agent used to treat various human cancers because of its antitumor activity. Unfortunately, up to 46% of the patients treated with bleomycin develop drug-induced interstitial lung disease (DIILD) and potentially life-threatening interstitial pulmonary fibrosis. Tools and biomarkers for predicting and detecting DIILD are limited.

Non-specific irreversible Zr-mAb uptake in tumours: evidence from biopsy-proven target-negative tumours using Zr-immuno-PET.

Background: Distribution of mAbs into tumour tissue may occur via different processes contributing differently to the Zr-mAb uptake on PET. Target-specific binding in tumours is of main interest; however, non-specific irreversible uptake may also be present, which influences quantification. The aim was to investigate the presence of non-specific irreversible uptake in tumour tissue using Patlak linearization on Zr-immuno-PET data of biopsy-proven target-negative tumours.

Validation of simplified uptake measures against dynamic Patlak K for quantification of lesional Zr-Immuno-PET antibody uptake.

Purpose: Positron emission tomography imaging of zirconium-89-labelled monoclonal antibodies (Zr-Immuno-PET) allows for visualisation and quantification of antibody uptake in tumours in vivo. Patlak linearization provides distribution volume (V) and nett influx rate (K) values, representing reversible and irreversible uptake, respectively. Standardised uptake value (SUV) and tumour-to-plasma/tumour-to-blood ratio (TPR/TBR) are often used, but their validity depends on the comparability of plasma kinetics and clearances.

Optimal imaging time points considering accuracy and precision of Patlak linearization for Zr-immuno-PET: a simulation study.

Purpose: Zirconium-89-immuno-positron emission tomography (Zr-immuno-PET) has enabled visualization of zirconium-89 labelled monoclonal antibody (Zr-mAb) uptake in organs and tumors in vivo. Patlak linearization of Zr-immuno-PET quantification data allows for separation of reversible and irreversible uptake, by combining multiple blood samples and PET images at different days. As one can obtain only a limited number of blood samples and scans per patient, choosing the optimal time points is important.

3D Convolutional Neural Network-Based Denoising of Low-Count Whole-Body F-Fluorodeoxyglucose and Zr-Rituximab PET Scans.

Acquisition time and injected activity of F-fluorodeoxyglucose (F-FDG) PET should ideally be reduced. However, this decreases the signal-to-noise ratio (SNR), which impairs the diagnostic value of these PET scans. In addition, Zr-antibody PET is known to have a low SNR.

Noise sensitivity of Zr-Immuno-PET radiomics based on count-reduced clinical images.

Purpose: Low photon count in Zr-Immuno-PET results in images with a low signal-to-noise ratio (SNR). Since PET radiomics are sensitive to noise, this study focuses on the impact of noise on radiomic features from Zr-Immuno-PET clinical images. We hypothesise that Zr-Immuno-PET derived radiomic features have: (1) noise-induced variability affecting their precision and (2) noise-induced bias affecting their accuracy.

Potential and pitfalls of Zr-immuno-PET to assess target status: Zr-trastuzumab as an example.

Background: Zirconium-immuno-positron emission tomography (Zr-immuno-PET) is used for assessment of target status to guide antibody-based therapy. We aim to determine the relation between antibody tumor uptake and target concentration to improve future study design and interpretation.

Methods: The relation between tumor uptake and target concentration was predicted by mathematical modeling of Zr-labeled antibody disposition in the tumor.

Optimizing Workflows for Fast and Reliable Metabolic Tumor Volume Measurements in Diffuse Large B Cell Lymphoma.

Purpose: This pilot study aimed to determine interobserver reliability and ease of use of three workflows for measuring metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in diffuse large B cell lymphoma (DLBCL).

Procedures: Twelve baseline [F]FDG PET/CT scans from DLBCL patients with wide variation in number and size of involved organs and lymph nodes were selected from the international PETRA consortium database. Three observers analyzed scans using three workflows.

Interobserver reproducibility of tumor uptake quantification with Zr-immuno-PET: a multicenter analysis.

Purpose: In-vivo quantification of tumor uptake of 89-zirconium (Zr)-labelled monoclonal antibodies (mAbs) with PET provides a potential tool in strategies to optimize tumor targeting and therapeutic efficacy. A specific challenge for Zr-immuno-PET is low tumor contrast. This is expected to result in interobserver variation in tumor delineation.

Zr-Immuno-PET: Toward a Noninvasive Clinical Tool to Measure Target Engagement of Therapeutic Antibodies In Vivo.

Zr-immuno-PET is a promising noninvasive clinical tool that measures target engagement of monoclonal antibodies (mAbs) to predict toxicity in normal tissues and efficacy in tumors. Quantification of Zr-immuno-PET will need to move beyond SUVs, since total uptake may contain a significant non-target-specific contribution. Nonspecific uptake is reversible (e.

Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images.

Purpose: Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET.

Assessment of target-mediated uptake with immuno-PET: analysis of a phase I clinical trial with an anti-CD44 antibody.

Background: Ideally, monoclonal antibodies provide selective treatment by targeting the tumour, without affecting normal tissues. Therefore, antibody imaging is of interest, preferably in early stages of drug development. However, the imaging signal consists of specific, as well as non-specific, uptake.

Performance of 89Zr-Labeled-Rituximab-PET as an Imaging Biomarker to Assess CD20 Targeting: A Pilot Study in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma.

Purpose: Treatment of patients with diffuse large B cell lymphoma (DLBCL) includes rituximab, an anti-CD20 monoclonal antibody (mAb). Insufficient tumor targeting might cause therapy failure. Tumor uptake of 89Zirconium (89Zr)-mAb is a potential imaging biomarker for tumor targeting, since it depends on target antigen expression and accessibility.

Immuno-Positron Emission Tomography with Zirconium-89-Labeled Monoclonal Antibodies in Oncology: What Can We Learn from Initial Clinical Trials?

Selection of the right drug for the right patient is a promising approach to increase clinical benefit of targeted therapy with monoclonal antibodies (mAbs). Assessment of in vivo biodistribution and tumor targeting of mAbs to predict toxicity and efficacy is expected to guide individualized treatment and drug development. Molecular imaging with positron emission tomography (PET) using zirconium-89 ((89)Zr)-labeled monoclonal antibodies also known as (89)Zr-immuno-PET, visualizes and quantifies uptake of radiolabeled mAbs.

Radiation dosimetry of 89Zr-labeled chimeric monoclonal antibody U36 as used for immuno-PET in head and neck cancer patients.

Unlabelled: Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter (89)Zr (half-life, 78.4 h) recently became available.

Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients.

Purpose: Immuno-positron emission tomography (PET), the combination of PET with monoclonal antibodies (mAb), is an attractive option to improve tumor detection and to guide mAb-based therapy. The long-lived positron emitter zirconium-89 ((89)Zr) has ideal physical characteristics for immuno-PET with intact mAbs but has never been used in a clinical setting. In the present feasibility study, we aimed to evaluate the diagnostic imaging performance of immuno-PET with (89)Zr-labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC), who were at high risk of having neck lymph node metastases.