AI Article Synopsis
- [F]MK-6240 is a PET tracer that targets neurofibrillary tangles linked to Alzheimer’s cognitive decline and has passed preclinical safety studies.
- In a rat study, no adverse effects were observed even at doses much higher than the expected clinical dosage, indicating safety for human use.
- Biodistribution studies in humans showed that [F]MK-6240 is safely distributed throughout the body, with effective radiation doses comparable to other similar tracers.
Article Abstract
Purpose: [F]MK-6240 is a selective, high-affinity positron emission tomography tracer for imaging neurofibrillary tangles, a key pathological signature that correlates with cognitive decline in Alzheimer disease. This report provides safety information from preclinical toxicology studies and first-in-human whole-body biodistribution and dosimetry studies of [F]MK-6240 for its potential application in human brain imaging studies.
Procedures: MK-6240 was administered intravenously (IV) in a 7-day rat toxicity study at × 50, × 100, and × 1000 dose margins relative to projected highest clinical dose of 0.333 μg/kg. The IV formulation of MK-6240 for clinical use and the formulation used in the 7-day rat toxicity study was tested for hemolysis potential in human and Wistar rat whole blood. Sequential whole-body positron emission tomography scans were performed in three healthy young subjects after IV bolus injection of 180 ± 0.3 MBq [F]MK-6240 to characterize organ biodistribution and estimate whole-body radiation exposure (effective dose).
Results: MK-6240 administered IV in a 7-day rat toxicity study did not show any test article-related changes. The no-observed-adverse-effect level in rats was ≥ 333 μg/kg/day which provides a margin 1000-fold over an anticipated maximum clinical dose of 0.333 μg/kg. Additionally, the MK-6240 formulation was not hemolytic in human or Wistar rat blood. [F]MK-6240 activity was widely distributed to the brain and the rest of the body, with organ absorbed doses largest for the gall bladder (202 μGy/MBq). The average (±SD) effective dose was 29.4 ± 0.6 μSv/MBq, which is in the typical range for F-18 radiolabeled ligands.
Conclusions: Microdoses of [F]MK-6240 are safe for clinical positron emission tomography imaging studies. Single IV administration of 185 MBq (5 mCi) [F]MK-6240 is anticipated to result in a total human effective dose of 5.4 mSv and thus allows multiple positron emission tomography scans of the same subject per year.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11307-019-01367-w | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular Stratification of Light-Chain Cardiac Amyloidosis With F-Florbetapir and Ga-FAPI-04 for Enhanced Prognostic Precision.
JACC Cardiovasc Imaging
January 2025
Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: Cardiac involvement in amyloid light chain (AL) amyloidosis significantly influences prognosis, necessitating timely diagnosis and meticulous risk stratification.
Objectives: This prospective study aimed to delineate the molecular phenotypes of AL cardiac amyloidosis (AL-CA) by characterizing fibro-amyloid deposition using F-florbetapir and gallium-68-labeled fibroblast activation protein inhibitor-04 (Ga-FAPI-04) positron emission tomography (PET)/computed tomography (CT) imaging. The authors also proposed a novel molecular stratification methodology for prognosis.
Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates.
Mol Ther
January 2025
Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, MA, USA, 02139; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; Cambridge, MA, USA, 02139; Department of Chemical Engineering, Massachusetts Institute of Technology; Cambridge, MA, USA, 02139; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University; Cambridge, MA, USA, 02139; Howard Hughes Medical Institute; Chevy Chase, MD, USA, 20815; Department of Materials Science of Engineering; Massachusetts Institute of Technology; Cambridge, MA, USA, 02139. Electronic address:
mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following i.
View Article and Find Full Text PDFPrediction of Persistent Tumor Status in Nasopharyngeal Carcinoma Post-Radiotherapy-Related Treatment: A Machine Learning Approach.
Cancers (Basel)
December 2024
Artificial Intelligence Center, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
The duration of the response to radiotherapy-related treatment is a critical prognostic indicator for patients with nasopharyngeal carcinoma (NPC). Persistent tumor status, including residual tumor presence and early recurrence, is associated with poorer survival outcomes. To address this, we developed a prediction model to identify patients at a high risk of persistent tumor status prior to initiating treatment.
View Article and Find Full Text PDFRobot-Assisted PSMA-Radioguided Salvage Surgery for Oligorecurrent Prostate Cancer Using the Novel SENSEI Drop-in Gamma Probe: Correlation of Intraoperative Measurements to Preoperative Imaging and Final Histology.
Cancers (Basel)
December 2024
Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.
Background: To examine the feasibility and safety of the SENSEI drop-in gamma probe for robot-assisted, prostate-specific membrane antigen (PSMA)-radioguided salvage surgery (RGS) in lymph node or local oligorecurrent prostate cancer (PCa), detected via PSMA positron emission tomography/computed tomography (PET/CT).
Methods: The first thirteen patients with pelvic oligorecurrent PCa who underwent [Tc]Tc-PSMA-I&S RGS using the SENSEI drop-in gamma probe at the Martini-Klinik (February-June 2024) were retrospectively analyzed. Radioactivity measurements in counts per second (CPS) as absolute values or ratios (CPS of tumor specimens/mean CPS from the patients' benign tissues) were correlated with preoperative imaging and pathological findings (benign/malignant, lesion size).
Prognostic Significance of Interim PET/CT in the First-Line Treatment of Follicular Lymphoma Patients, a Single-Center Experience.
Cancers (Basel)
December 2024
Department of Hematology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
: Follicular lymphoma (FL) is a heterogeneous disease, and identifying high-risk patients early is crucial for optimal management. This study aimed to evaluate the prognostic significance of interim positron emission tomography/computed tomography (PET/CT) in newly diagnosed FL patients undergoing first-line treatment. : This single-center, retrospective study included 103 patients with newly diagnosed FL who underwent interim PET/CT.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!