Diagnosis of Prostate Cancer with a Neurotensin-Bombesin Radioligand Combination-First Preclinical Results.

The concept of radiotheranostics relies on the overexpression of a biomolecular target on malignant cells to direct diagnostic/therapeutic radionuclide-carriers specifically to cancer lesions. The concomitant expression of more than one target in pathological lesions may be elegantly exploited to improve diagnostic sensitivity and therapeutic efficacy. Toward this goal, we explored a first example of a combined application of [Tc]Tc-DT11 (DT11, N-Lys(MPBA-PEG4)-Arg-Arg-Pro-Tyr-Ile-Leu-OH; NTSR-specific) and [Tc]Tc-DB7(DB7, N-PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; GRPR-specific) in prostate cancer models.

Mesenchymal Stem Cell Transplantation Has a Regenerative Effect in Ischemic Myocardium: An Experimental Rat Model Evaluated by SPECT-CT Assessment.

Unlabelled: Translational perspective: Ischemic heart disease remains a major medical problem with high mortality rates. Beside the great efforts devoted to research worldwide and the use of numerous experimental models, an absolute understanding of myocardial infarction and tissue loss has not yet been achieved. Furthermore, the regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in the medical (and especially cardiovascular) community.

Side-Chain Modified [Tc]Tc-DT1 Mimics: A Comparative Study in NTSR-Positive Models.

Radiolabeled neurotensin analogs have been developed as candidates for theranostic use against neurotensin subtype 1 receptor (NTSR)-expressing cancer. However, their fast degradation by two major peptidases, neprilysin (NEP) and angiotensin-converting enzyme (ACE), has hitherto limited clinical success. We have recently shown that palmitoylation at the -amine of Lys in [Tc]Tc-[Lys]DT1 (DT1, N-Gly-Arg-Arg-Pro-Tyr-Ile-Leu-OH, N = 6-(carboxy)-1,4,8,11-tetraazaundecane) led to the fully stabilized [Tc]Tc-DT9 analog, displaying high uptake in human pancreatic cancer AsPC-1 xenografts but unfavorable pharmacokinetics in mice.

Α Humanized RANKL Transgenic Mouse Model of Progestin-Induced Mammary Carcinogenesis for Evaluation of Novel Therapeutics.

Receptor activator of nuclear factor-κB ligand (RANKL) is critically involved in mammary gland pathophysiology, while its pharmaceutical inhibition is being currently investigated in breast cancer. Herein, we investigated whether the overexpression of human RANKL in transgenic mice affects hormone-induced mammary carcinogenesis, and evaluated the efficacy of anti-RANKL treatments, such as OPG-Fc targeting both human and mouse RANKL or Denosumab against human RANKL. We established novel MPA/DMBA-driven mammary carcinogenesis models in TgRANKL mice that express both human and mouse RANKL, as well as in humanized humTgRANKL mice expressing only human RANKL, and compared them to MPA/DMBA-treated wild-type (WT) mice.

[In]In/[Lu]Lu-AAZTA-LM4 SSTR-Antagonists in Cancer Theranostics: From Preclinical Testing to First Patient Results.

Aiming to expand the application of the SSTR-antagonist LM4 (DPhe-c[DCys-4Pal-DAph(Cbm)-Lys-Thr-Cys]-DTyr-NH) beyond [Ga]Ga-DATA-LM4 PET/CT (DATA, (6-pentanoic acid)-6-(amino)methy-1,4-diazepinetriacetate), we now introduce AAZTA-LM4 (AAZTA, 1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)]amino-6-[pentanoic-acid]perhydro-1,4-diazepine), allowing for the convenient coordination of trivalent radiometals of clinical interest, such as In-111 (for SPECT/CT) or Lu-177 (for radionuclide therapy). After labeling, the preclinical profiles of [In]In-AAZTA-LM4 and [Lu]Lu-AAZTA-LM4 were compared in HEK293-SSTR cells and double HEK293-SSTR/wtHEK293 tumor-bearing mice using [In]In-DOTA-LM3 and [Lu]Lu-DOTA-LM3 as references. The biodistribution of [Lu]Lu-AAZTA-LM4 was additionally studied for the first time in a NET patient.

A Novel Experimental Rat Model for the Assessment of Myocardial Ischemia Based on Single Photon Emission Computed Tomography.

Background/aim: Myocardial infarction, an acute medical situation with a high mortality rate worldwide, has been extensively studied in modern cardiovascular research, using different experimental models. However, a deep understanding of myocardial activity loss has not been fully investigated. We have developed a novel experimental rat model for noninvasive assessment of myocardial ischemia based on single photon emission computed tomography (SPECT/CT), in order to further understand and evaluate myocardial activity before and after surgical induction of myocardial ischemia.

In vivo biodistribution of edelfosine-loaded lipid nanoparticles radiolabeled with Technetium-99 m: Comparison of administration routes in mice.

Edelfosine (ET) is a potent antitumor agent but causes severe side effects that have limited its use in clinical practice. For this reason, nanoencapsulation in lipid nanoparticles (LNs) is advantageous as it protects from ET side-effects. Interestingly, previous studies showed the efficacy of LNs containing ET in various types of tumor.

Nonpeptidic Z360-Analogs Tagged with Trivalent Radiometals as Anti-CCKR Cancer Theranostic Agents: A Preclinical Study.

(1) Background: Theranostic approaches in the management of cholecystokinin subtype 2 receptor (CCKR)-positive tumors include radiolabeled gastrin and CCK motifs. Moving toward antagonist-based CCKR-radioligands instead, we herein present three analogs of the nonpeptidic CCKR-antagonist Z360, GAS1/2/3. Each was conjugated to a different chelator (DOTA, NODAGA or DOTAGA) for labeling with medically relevant trivalent radiometals (e.

Optical to Planar X-ray Mouse Image Mapping in Preclinical Nuclear Medicine Using Conditional Adversarial Networks.

In the current work, a pix2pix conditional generative adversarial network has been evaluated as a potential solution for generating adequately accurate synthesized morphological X-ray images by translating standard photographic images of mice. Such an approach will benefit 2D functional molecular imaging techniques, such as planar radioisotope and/or fluorescence/bioluminescence imaging, by providing high-resolution information for anatomical mapping, but not for diagnosis, using conventional photographic sensors. Planar functional imaging offers an efficient alternative to biodistribution ex vivo studies and/or 3D high-end molecular imaging systems since it can be effectively used to track new tracers and study the accumulation from zero point in time post-injection.

Using kinetic Monte Carlo simulations to design efficient magnetic nanoparticles for clinical hyperthermia.

Purpose: The purpose of this study was to identify the properties of magnetite nanoparticles that deliver optimal heating efficiency, predict the geometrical characteristics to get these target properties, and determine the concentrations of nanoparticles required to optimize thermotherapy.

Methods: Kinetic Monte Carlo simulations were employed to identify the properties of magnetic nanoparticles that deliver high Specific Absorption Rate (SAR) values. Optimal volumes were determined for anisotropies ranging between 11 and 40 kJ/m under clinically relevant magnetic field conditions.

Magnetic and radio-labeled bio-hybrid scaffolds to promote and track the progress of bone regeneration.

This work describes the preparation, characterization and functionalization with magnetic nanoparticles of a bone tissue-mimetic scaffold composed of collagen and hydroxyapatite obtained through a biomineralization process. Bone remodeling takes place over several weeks and the possibility to follow it in a quick and reliable way is still an outstanding issue. Therefore, this work aims to produce an implantable material that can be followed during bone regeneration by using the existing non-invasive imaging techniques (MRI).

An in-silico method to predict and quantify the effect of gold nanoparticles in X-ray imaging.

Purpose: Over the last few years studies are conducted, highlighting the feasibility of Gold Nanoparticles (GNPs) to be used in clinical CT imaging and as an efficient contrast agent for cancer research. After ensuring that GNPs formulations are appropriate for in vivo or clinical use, the next step is to determine the parameters for an X-ray system's optimal contrast for applications and to extract quantitative information. There is currently a gap and need to exploit new X-ray imaging protocols and processing algorithms, through specific models avoiding trial-and-error procedures and provide an imaging prognosis tool.

Advanced Monte Carlo simulations of emission tomography imaging systems with GATE.

Built on top of the Geant4 toolkit, GATE is collaboratively developed for more than 15 years to design Monte Carlo simulations of nuclear-based imaging systems. It is, in particular, used by researchers and industrials to design, optimize, understand and create innovative emission tomography systems. In this paper, we reviewed the recent developments that have been proposed to simulate modern detectors and provide a comprehensive report on imaging systems that have been simulated and evaluated in GATE.

IDDRRA: A novel platform, based on Geant4-DNA to quantify DNA damage by ionizing radiation.

Purpose: This study proposes a novel computational platform that we refer to as IDDRRA (DNA Damage Response to Ionizing RAdiation), which uses Monte Carlo (MC) simulations to score radiation induced DNA damage. MC simulations provide results of high accuracy on the interaction of radiation with matter while scoring the energy deposition based on state-of-the-art physics and chemistry models and probabilistic methods.

Methods: The IDDRRA software is based on the Geant4-DNA toolkit together with new tools that were developed for the purpose of this study, including a new algorithm that was developed in Python for the design of the DNA molecules.

One Step Closer to Clinical Translation: Enhanced Tumor Targeting of [Tc]Tc-DB4 and [In]In-SG4 in Mice Treated with Entresto.

Background: Peptide radioligands may serve as radionuclide carriers to tumor sites overexpressing their cognate receptor for diagnostic or therapeutic purposes. Treatment of mice with the neprilysin (NEP)-inhibitor phosphoramidon was previously shown to improve the metabolic stability and tumor uptake of biodegradable radiopeptides. Aiming to clinical translation of this methodology, we herein investigated the impact of the approved pill Entresto, releasing the potent NEP-inhibitor LBQ657 in vivo, on the stability and tumor uptake of two radiopeptides.

Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis.

Background: The transmembrane-TNF transgenic mouse, TgA86, has been shown to develop spontaneously peripheral arthritis with signs of axial involvement. To assess similarity to human spondyloarthritis, we performed detailed characterization of the axial, peripheral, and comorbid pathologies of this model.

Methods: TgA86 bone pathologies were assessed at different ages using CT imaging of the spine, tail vertebrae, and hind limbs and characterized in detail by histopathological and immunohistochemical analysis.

Conjugated Photosensitizers for Imaging and PDT in Cancer Research.

Early cancer detection and perfect understanding of the disease are imperative toward efficient treatments. It is straightforward that, for choosing a specific cancer treatment methodology, diagnostic agents undertake a critical role. Imaging is an extremely intriguing tool since it assumes a follow up to treatments to survey the accomplishment of the treatment and to recognize any conceivable repeating injuries.

[Tc]Tc-DGA1, a Promising CCKR-Antagonist-Based Tracer for Tumor Diagnosis with Single-Photon Emission Computed Tomography.

Radiolabeled gastrin analogues have been proposed for theranostics of cholecystokinin subtype 2 receptor (CCKR)-positive cancer. Peptide radioligands based on other receptor antagonists have displayed superior pharmacokinetics and higher biosafety than agonists. Here, we present DGA1, a derivative of the nonpeptidic CCKR antagonist Z-360 carrying an acyclic tetraamine, for [Tc]Tc labeling.

imaging techniques for bone tissue engineering.

Bone is a dynamic tissue that constantly undergoes modeling and remodeling. Bone tissue engineering relying on the development of novel implant scaffolds for the treatment of pre-clinical bone defects has been extensively evaluated by histological techniques. The study of bone remodeling, that takes place over several weeks, is limited by the requirement of a large number of animals and time-consuming and labor-intensive procedures.

Exploration of New Contrasts, Targets, and MR Imaging and Spectroscopy Techniques for Neuromuscular Disease - A Workshop Report of Working Group 3 of the Biomedicine and Molecular Biosciences COST Action BM1304 MYO-MRI.

Neuromuscular diseases are characterized by progressive muscle degeneration and muscle weakness resulting in functional disabilities. While each of these diseases is individually rare, they are common as a group, and a large majority lacks effective treatment with fully market approved drugs. Magnetic resonance imaging and spectroscopy techniques (MRI and MRS) are showing increasing promise as an outcome measure in clinical trials for these diseases.

Quantification of DNA double-strand breaks using Geant4-DNA.

Purpose: This study aims to standardize the simulation procedure in measuring DNA double-strand breaks (DSBs), by using advanced Monte Carlo toolkits, and newly introduced experimental methods for DNA DSB measurement.

Methods: For the experimental quantification of DNA DSB, an innovative DNA dosimeter was used to produce experimental data. GATE in combination with Geant4-DNA toolkit were exploited to simulate the experimental environment.

A personalized, Monte Carlo-based method for internal dosimetric evaluation of radiopharmaceuticals in children.

Purpose: Herein, we introduce a methodology for estimating the absorbed dose in organs at risk that is based on specified clinically derived radiopharmaceutical biodistributions and personalized anatomical characteristics.

Methods: To evaluate the proposed methodology, we used realistic Monte Carlo (MC) simulations and computational pediatric models to calculate a parameter called in this work the "specific absorbed dose rate" (SADR). The SADR is a unique quantitative metric in that it is specific to a particular organ.

Iron Oxide Colloidal Nanoclusters as Theranostic Vehicles and Their Interactions at the Cellular Level.

Advances in surfactant-assisted chemical approaches have led the way for the exploitation of nanoscale inorganic particles in medical diagnosis and treatment. In this field, magnetically-driven multimodal nanotools that perform both detection and therapy, well-designed in size, shape and composition, are highly advantageous. Such a theranostic material—which entails the controlled assembly of smaller (maghemite) nanocrystals in a secondary motif that is highly dispersible in aqueous media—is discussed here.