Recent Advances on Pt-Based Compounds for Theranostic Applications.

Since the discovery of cisplatin's antitumoral activity and its approval as an anticancer drug, significant efforts have been made to enhance its physiological stability and anticancer efficacy and to reduce its side effects. With the rapid development of targeted and personalized therapies, and the promising theranostic approach, platinum drugs have found new opportunities in more sophisticated systems. Theranostic agents combine diagnostic and therapeutic moieties in one scaffold, enabling simultaneous disease monitoring, therapy delivery, response tracking, and treatment efficacy evaluation.

Characterization of a Syngeneic Orthotopic Model of Cholangiocarcinoma by [F]FDG-PET/MRI.

Cholangiocarcinoma (CCA) is a type of primary liver cancer originating from the biliary tract epithelium, characterized by limited treatment options for advanced cases and low survival rates. This study aimed to establish an orthotopic mouse model for CCA and monitor tumor growth using PET/MR imaging. Murine CCA cells were implanted into the liver lobe of male C57BL/6J mice.

Preclinical SPECT and PET: Joint EANM and ESMI procedure guideline for implementing an efficient quality control programme.

The aim of this guideline is to provide recommendations for the implementation of an effective and efficient quality control (QC) programme for SPECT and PET systems in a preclinical imaging lab. These recommendations aim to strengthen the translational power of preclinical imaging results obtained using preclinical SPECT and PET. As for clinical imaging, reliability, reproducibility, and repeatability are essential when groups of animals are used in a longitudinal imaging experiment.

Optimizing SUV Analysis: A Multicenter Study on Preclinical FDG-PET/CT Highlights the Impact of Standardization.

Purpose: Preclinical imaging, with translational potential, lacks a standardized method for defining volumes of interest (VOIs), impacting data reproducibility. The aim of this study was to determine the interobserver variability of VOI sizes and standard uptake values (SUV and SUV) of different organs using the same [F]FDG-PET and PET/CT datasets analyzed by multiple observers. In addition, the effect of a standardized analysis approach was evaluated.

Functionalization of Ga-Radiolabeled Nanodiamonds with Octreotide Does Not Improve Tumor-Targeting Capabilities.

Nanodiamonds (NDs) are emerging as a novel nanoparticle class with growing interest in medical applications. The surface coating of NDs can be modified by attaching binding ligands or imaging probes, turning them into multi-modal targeting agents. In this investigation, we assessed the targeting efficacy of octreotide-functionalized Ga-radiolabelled NDs for cancer imaging and compared it with the tumor uptake using [Ga]Ga-DOTA-TOC.

Tailoring the Mass Density of 3D Printing Materials for Accurate X-ray Imaging Simulation by Controlled Underfilling for Radiographic Phantoms.

Additive manufacturing and 3D printing allow for the design and rapid production of radiographic phantoms for X-ray imaging, including CT. These are used for numerous purposes, such as patient simulation, optimization of imaging procedures and dose levels, system evaluation and quality assurance. However, standard 3D printing polymers do not mimic X-ray attenuation properties of tissues like soft, adipose, lung or bone tissue, and standard materials like liquid water.

Positron Emission Tomography-Based Pharmacokinetic Analysis To Assess Renal Transporter-Mediated Drug-Drug Interactions of Antimicrobial Drugs.

Transporter-mediated drug-drug interactions (DDIs) are of concern in antimicrobial drug development, as they can have serious safety consequences. We used positron emission tomography (PET) imaging-based pharmacokinetic (PK) analysis to assess the effect of different drugs, which may cause transporter-mediated DDIs, on the tissue distribution and excretion of [F]ciprofloxacin as a radiolabeled model antimicrobial drug. Mice underwent PET scans after intravenous injection of [F]ciprofloxacin, without and with pretreatment with either probenecid (150 mg/kg), cimetidine (50 mg/kg), or pyrimethamine (5 mg/kg).

Synthesis, radiolabeling, and preclinical in vivo evaluation of Ga-radiolabelled nanodiamonds.

Purpose: Nanodiamonds (NDs) represent a new class of nanoparticles and have gained increasing interest in medical applications. Modifying the surface coating by attaching binding ligands or imaging probes can transform NDs into multi-modal targeting probes. This study evaluated the biokinetics and biodistribution of Ga-radiolabelled NDs in a xenograft model.

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.

Use of PET Imaging to Assess the Efficacy of Thiethylperazine to Stimulate Cerebral MRP1 Transport Activity in Wild-Type and APP/PS1-21 Mice.

Multidrug resistance-associated protein 1 (MRP1, encoded by the gene) may contribute to the clearance of amyloid-beta (Aβ) peptides from the brain into the blood and stimulation of MRP1 transport activity may be a therapeutic approach to enhance brain Aβ clearance. In this study, we assessed the effect of thiethylperazine, an antiemetic drug which was shown to stimulate MRP1 activity in vitro and to decrease Aβ load in a rapid β-amyloidosis mouse model (APP/PS1-21), on MRP1 transport activity by means of positron emission tomography (PET) imaging with the MRP1 tracer 6-bromo-7-[C]methylpurine. Groups of wild-type, APP/PS1-21 and mice underwent PET scans before and after a 5-day oral treatment period with thiethylperazine (15 mg/kg, once daily).

Characterization of an APP/tau rat model of Alzheimer's disease by positron emission tomography and immunofluorescent labeling.

Background: To better understand the etiology and pathomechanisms of Alzheimer's disease, several transgenic animal models that overexpress human tau or human amyloid-beta (Aβ) have been developed. In the present study, we generated a novel transgenic rat model by cross-breeding amyloid precursor protein (APP) rats with tau rats. We characterized this model by performing positron emission tomography scans combined with immunofluorescent labeling and cerebrospinal fluid analyses.

Assessing the Functional Redundancy between P-gp and BCRP in Controlling the Brain Distribution and Biliary Excretion of Dual Substrates with PET Imaging in Mice.

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are co-localized at the blood-brain barrier, where they display functional redundancy to restrict the brain distribution of dual P-gp/BCRP substrate drugs. We used positron emission tomography (PET) with the metabolically stable P-gp/BCRP substrates [C]tariquidar, [C]erlotinib, and [C]elacridar to assess whether a similar functional redundancy as at the BBB exists in the liver, where both transporters mediate the biliary excretion of drugs. Wild-type, , , and mice underwent dynamic whole-body PET scans after i.

Vitamin K chloro derivative (VKT-2) inhibits HDAC6, activates autophagy and apoptosis, and inhibits aggresome formation in hepatocellular carcinoma cells.

Epigenetics plays a vital role in regulating gene expression and determining the specific phenotypes of eukaryotic cells. Histone deacetylases (HDACs) are important epigenetic regulatory proteins effecting multiple biological functions. Particularly, HDAC6 has become a promising anti-cancer drug target because of its regulation of cell mobility, protein trafficking, degradation of misfolded proteins, cell growth, apoptosis, and metastasis.

Plasma pharmacokinetic and metabolism of [F]THK-5317 are dependent on sex.

Introduction: Tau deposition is one of the hallmarks of Alzheimer's disease (AD) and can be visualized and quantified using [F]THK-5317 together with kinetic modeling. To determine the feasibility of this approach, we measured blood/plasma pharmacokinetics and radiotracer metabolism in female and male rats.

Methods: Female and male rats (n = 11-12) were cannulated via the femoral artery for continuous blood sampling.

Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study.

The standardization of preclinical imaging is a key factor to ensure the reliability, reproducibility, validity, and translatability of preclinical data. Preclinical standardization has been slowly progressing in recent years and has mainly been performed within a single institution, whereas little has been done in regards to multicenter standardization between facilities. This study aimed to investigate the comparability among preclinical imaging facilities in terms of PET data acquisition and analysis.

Real-time data-driven motion correction in PET.

PET imaging has been, and continues to be, an evolving diagnostic technology. In recent years, the modernizing digital landscape has opened new opportunities for data-driven innovation. One such facet has been data-driven motion correction (DDMC) in PET.

Influence of Multidrug Resistance-Associated Proteins on the Excretion of the ABCC1 Imaging Probe 6-Bromo-7-[C]Methylpurine in Mice.

Purpose: Multidrug resistance-associated proteins (MRPs) mediate the hepatobiliary and renal excretion of many drugs and drug conjugates. The positron emission tomography (PET) tracer 6-bromo-7-[C]methylpurine is rapidly converted in tissues by glutathione-S-transferases into its glutathione conjugate, and has been used to measure the activity of Abcc1 in the brain and the lungs of mice. Aim of this work was to investigate if the activity of MRPs in excretory organs can be measured with 6-bromo-7-[C]methylpurine.

Influence of breast cancer resistance protein and P-glycoprotein on tissue distribution and excretion of Ko143 assessed with PET imaging in mice.

Ko143 is a reference inhibitor of the adenosine triphosphate-binding cassette (ABC) transporter breast cancer resistance protein (humans: ABCG2, rodents: Abcg2) for in vitro and in vivo use. Previous in vitro data indicate that Ko143 binds specifically to ABCG2/Abcg2, suggesting a potential utility of Ko143 as a positron emission tomography (PET) tracer to assess the density (abundance) of ABCG2 in different tissues. In this work we radiolabeled Ko143 with carbon-11 (C) and performed small-animal PET experiments with [C]Ko143 in wild-type, Abcg2, Abcb1a/b and Abcb1a/bAbcg2 mice to assess the influence of Abcg2 and Abcb1a/b on tissue distribution and excretion of [C]Ko143.

[F]Fluoroalkyl azides for rapid radiolabeling and (Re)investigation of their potential towards in vivo click chemistry.

In recent years, radiofluorinated alkyl azides have been reported for click radiolabeling and pretargeted PET imaging, but only little is known about the biodistribution and metabolism of these compounds. In this work, we present a significantly improved procedure for the synthesis of [F]fluoroethyl azide and reinvestigated this radiolabeled probe in detail showing poor stability and very restricted suitability for in vivo application. Therefore, modified low-molecular-weight [F]fluoroalkyl azides were developed.

[C]Erlotinib PET cannot detect acquired erlotinib resistance in NSCLC tumor xenografts in mice.

Introduction: [C]Erlotinib PET has shown promise to distinguish non-small cell lung cancer (NSCLC) tumors harboring the activating epidermal growth factor receptor (EGFR) mutation delE746-A750 from tumors with wild-type EGFR. To assess the suitability of [C]erlotinib PET to detect the emergence of acquired erlotinib resistance in initially erlotinib-responsive tumors, we performed in vitro binding and PET experiments in mice bearing tumor xenografts using a range of different cancer cells, which were erlotinib-sensitive or exhibited clinically relevant resistance mechanisms to erlotinib.

Methods: The following cell lines were used for in vitro binding and PET experiments: the epidermoid carcinoma cell line A-431 (erlotinib-sensitive, wild-type EGFR) and the three NSCLC cell lines HCC827 (erlotinib-sensitive, delE746-A750), HCC827 (erlotinib-resistant, delE746-A750 and T790M) and HCC827 (erlotinib-resistant, delE746-A750 and MET amplification).

On the applicability of [F]FBPA to predict L-BPA concentration after amino acid preloading in HuH-7 liver tumor model and the implication for liver boron neutron capture therapy.

Introduction: In recent years extra-corporal application of boron neutron capture therapy (BNCT) was evaluated for liver primary tumors or liver metastases. A prerequisite for such a high-risk procedure is proof of preferential delivery and high uptake of a B-pharmaceutical in liver malignancies. In this work we evaluated in a preclinical tumor model if [F]FBPA tissue distribution measured with PET is able to predict the tissue distribution of [B]L-BPA.

Guidance for Efficient Small Animal Imaging Quality Control.

Routine quality control is a critical aspect of properly maintaining high-performance small animal imaging instrumentation. A robust quality control program helps produce more reliable data both for academic purposes and as proof of system performance for contract imaging work. For preclinical imaging laboratories, the combination of costs and available resources often limits their ability to produce efficient and effective quality control programs.