Bioinspired Synthesis of Intrinsically Radiolabeled DyO Nanoparticles as an In Vivo Generator of Dy/Ho: A Smart Choice for Theranostics Engineering.

Functionalized inorganic nanoparticles (NPs) intrinsically radiolabeled with theranostic radiometals hold the potential to revolutionize cancer management. The appropriate choice of the radiometal used in the nanoplatform would not only aid in the diagnosis and staging of the disease but also facilitate them becoming an integral part of the therapeutic regimen, either as an independent treatment or in combination with other conventional modalities. Furthermore, due to the inherent characteristics of the NPs, such systems can demonstrate potential in multimodality imaging to offer improved diagnostic and therapeutic monitoring abilities for personalized treatment.

Convenient one-pot synthesis of 1-(4-(4-(2-[F]fluoroethoxy)phenyl)piperazin-1-yl)ethanone ([F]FEt-PPZ) for imaging tumors expressing sigma-1 receptors.

The overexpression of the sigma-1 receptor (σ1R) in a variety of cancers makes it a potential target for developing anticancer drugs or diagnostic/therapeutic radiopharmaceuticals. Molecules with piperidine or piperazine substructures have shown high binding affinity towards σ1R. Docking and MD simulation studies on commercially available piperidine/piperazine-containing compounds identified 1-(4-(4-hydroxyphenyl)piperazin-1-yl)ethanone (PPZ) as a potential ligand for targeting σ1R.

Dy/Ho-labeled porous hydroxyapatite microparticles for treatment of inflammatory joint diseases - Exploring the advantages of in vivo generator.

Holmium-166 [T = 26.8 h, E (max) = 1.74 MeV (48.

On the automated radiosynthesis of pharmaceutical grade [Ga]Ga-Pentixafor, its pre-clinical evaluation, clinical application and radiation dosimetry aspects.

The current study outlines a consistent and reproducible protocol for the routine clinical dose preparation of [Ga]Ga-Pentixafor using the Eckert and Ziegler 'Modular-Lab Standard' non-cassette based automated module, that can be effectively used in the hospital radiopharmacy unit of a high volume nuclear medicine centre. The pre-clinical studies (including in-vitro cell line studies, in-vivo PET/CT imaging and pre-clinical dosimetry) were conducted to show the promising potential of the product for clinical use in targeting CXCR4 tumor overexpression. PET/CT image of SCID mouse bearing lymphoma xenograft tumor, at 2 h post-injection, clearly delineated the tumor.

Protein-functionalized and intrinsically radiolabeled [Re]ReO nanoparticles: advancing cancer therapy through concurrent radio-photothermal effects.

Purpose: Enhancing therapeutic effectiveness is crucial for translating anticancer nanomedicines from laboratory to clinical settings. In this study, we have developed radioactive rhenium oxide nanoparticles encapsulated in human serum albumin ([Re]ReO-HSA NPs) for concurrent radiotherapy (RT) and photothermal therapy (PTT), aiming to optimize treatment outcomes.

Methods: [Re]ReO-HSA NPs were synthesized by a controlled reduction of ReO in HSA medium and extensively characterized.

Chlorambucil Conjugation Enhances the Potency of Rituximab: Synthesis and Evaluation of the Novel [Lu]Lu-Labeled Rituximab-Chlorambucil Conjugate toward Therapy of Non-Hodgkin's Lymphoma.

In this study, a novel antibody-drug conjugate (ADC) consisting of Rituximab and Chlorambucil (Rituximab-CMB) was synthesized. The average number of drug molecules attached per Rituximab molecule was determined using MALDI-TOF mass spectrometry, revealing a range of 4-6 drug molecules per antibody. To further improve the therapeutic potential of the ADC, it was radiolabeled with the therapeutic radionuclide Lu via a DOTA chelator, achieving a final radiochemical purity of over 95%.

Systemic Cancer Hallmarks as Novel Markers Associated with Progression-Free Survival in Gastroenteropancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy.

Introduction: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors often detected at the metastatic stage. The aim of this study was to profile the peripheral blood transcriptome through RNA-Seq and investigate the association of the systemic cancer hallmarks with progression-free survival, in peptide receptor radionuclide therapy (PRRT)-treated GEP-NET patients.

Methods: The cohorts were discovery cohort [PRRT-naïve well-differentiated GEP-NETs, n = 59; age- and sex-matched healthy individuals, n = 38], and independent evaluation cohort [GEP-NETs, n = 66].

Developing a peripheral blood RNA-seq based NETseq ensemble classifier: A potential novel tool for non-invasive detection and treatment response assessment in neuroendocrine tumor patients receiving Lu-DOTATATE PRRT.

Neuroendocrine tumors (NETs) are presented with metastases due to delayed diagnosis. We aimed to identify NET-related biomarkers from peripheral blood. The development and validation of a multi-gene NETseq ensemble classifier using peripheral blood RNA-Seq is reported.

pH-Responsive magnetic nanocarriers for chelator-free bimodal (MRI/SPECT-CT) image-guided chemo-hyperthermia therapy in human breast carcinoma.

Although chemotherapy with magnetic nanocarriers has witnessed significant advancement in the field of cancer treatment, multimodal diagnosis and combinatorial therapy using a single nanoplatform will have much better efficacy in achieving superior results. Herein, we constructed a smart theranostic system by combining pH-sensitive tartaric acid-stabilized FeO magnetic nanocarriers (TMNCs) with SPECT imaging and a chemotherapeutic agent for image-guided chemo-hyperthermia therapy. The carboxyl-enriched exteriors of TMNCs provided sites for the conjugation of a chemotherapeutic drug (doxorubicin hydrochloride, DOX) and radiolabeling (Ce).

On the Optimization of the Protocol for Automated Radiosyntheses of [Ga]Ga-Pentixafor, [Ga]Ga-FAPI-4 and [Ga]Ga-DOTATATE in a Modular-Lab Standard.

Objectives: The present work describes the automated radiochemical synthesis of different PET tracers like [Ga]Ga-Pentixafor, [Ga]Ga-FAPI-4 and [Ga]Ga-DOTATATE using optimized single protocol in the non-cassette based Eckert & Ziegler (EZ) Modular Lab (fixed tubing system) without any modification in the inbuilt human machine interface (HMI) software. Recently, PET agents viz. [Ga]Ga-Pentixafor and [Ga]Ga-FAPI-4 are gaining prominence for the diagnosis of overexpressed Chemokine Receptor-4 (CXCR4) and Fibroblast Activation Protein (FAP) receptor, respectively, in the microenvironment of numerous cancer types.

Methotrexate-Loaded Surface-Modified Solid Lipid Nanoparticles Targeting Cancer Expressing COX-2 Enzyme.

Cancer is a major public health problem worldwide, and it is the second leading cause of death of humans in the world. The present study has been directed toward the preparation of methotrexate-loaded surface-modified solid lipid nanoparticles (SLNs) for potential use as a chemotherapeutic formulation for cancer therapy. A lipid (C-AAP) derived from myristic acid (CHO) and acetaminophen (AAP) was employed as a targeting ligand for human breast and lung cancer cells that overexpress the cyclooxygenases-2 (COX-2) enzyme.

Delivery of Chlorambucil to the Brain Using Surface Modified Solid Lipid Nanoparticles.

The delivery of drugs to the brain in the therapy of diseases of the central nervous system (CNS) remains a continuing challenge because of the lack of delivery systems that can cross the blood-brain barrier (BBB). Therefore, there is a need to develop an innovative delivery method for the treatment of CNS diseases. Thus, we have investigated the interaction of γ-aminobutyric acid (GABA) and S-(-)-γ-amino-α-hydroxybutyric acid (GAHBA) with the GABA receptor by performing a docking study.

ZnAlO:Er Upconversion Nanophosphor for SPECT Imaging and Luminescence Modulation via Defect Engineering.

This work reports an "all-in-one" theranostic upconversion luminescence (UCL) system having potential for both diagnostic and therapeutic applications. Despite considerable efforts in designing upconversion nanoparticles (UCNPs) for multimodal imaging and tumor therapy, there are few reports investigating dual modality SPECT/optical imaging for theranostics. Especially, research focusing on in vivo biodistribution studies of intrinsically radiolabeled UCNPs after intravenous injection is of utmost importance for the potential clinical translation of such formulations.

Nuclear Localization Signal Enhances the Targeting and Therapeutic Efficacy of a Porphyrin-Based Molecular Cargo: A Systemic In Vitro and Ex Vivo Evaluation.

The objective of the present work was to evaluate the potential of a nuclear localization signal (NLS) toward facilitating intracellular delivery and enhancement in the therapeutic efficacy of the molecular cargo. Toward this, an in-house synthesized porphyrin derivative, namely, 5-carboxymethyelene-oxyphenyl-10,15,20-(4-methoxyphenyl) porphyrin (UTriMA), was utilized for conjugation with the NLS sequence [PKKKRKV]. The three compounds synthesized during the course of the present work, namely DOTA-Lys-NLS, DOTA-UTriMA-Lys-NLS, and DOTA-Lys-UTriMA, were evaluated for cellular toxicity in cancer cell lines (HT1080), wherein all exhibited minimal dark toxicity.

Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [Yb]YbO nanoseeds.

Purpose: Classical brachytherapy of solid malignant tumors is an invasive procedure which often results in an uneven dose distribution, while requiring surgical removal of sealed radioactive seed sources after a certain period of time. To circumvent these issues, we report the synthesis of intrinsically radiolabeled and gum Arabic glycoprotein functionalized [Yb]YbO nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy.

Methods: Yb (T = 32 days) was produced by neutron irradiation of enriched (15.

Intricacies in the Preparation of Patient Doses of [Lu]Lu-Rituximab and [Lu]Lu-Trastuzumab Using Low Specific Activity [Lu]LuCl: Methodological Aspects.

The development of humanized monoclonal antibodies (MAbs) with Lutetium-177 ([Lu]Lu) has brought a paradigm shift in the arena of targeted therapy of various cancers. [Lu]Lu-DOTA-Rituximab and [Lu]Lu-DOTA-Trastuzumab have gained prominence due to their improved therapeutic efficacy in the treatment of lymphoma and breast cancer. The clinical dose formulation of these radiolabeled MAbs, using low specific activity [Lu]LuCl, requires extensive optimization of the radiolabeling protocol.

Physicochemical Characterization, Stability, and In Vitro Evaluation of Curcumin-Loaded Solid Lipid Nanoparticles Prepared Using Biocompatible Synthetic Lipids.

Solid lipid nanoparticles (SLNs) are promising drug delivery vehicles for the delivery of various drugs, especially poorly water-soluble drugs. However, the aqueous stability, drug release, and biocompatibility of SLNs are some of the issues that need attention. In this work, curcumin-loaded SLNs were prepared, and morphology, particle size, and entrapment efficiency were studied.

Synthesis and Lu Labeling of the First Retro Analog of the HER2-Targeting A9 Peptide: A Superior Variant.

The retro analog of the HER2-targeting A9 peptide was synthesized by coupling amino acids in a reverse fashion and switching the N-terminal in the original sequence of the L-A9 peptide (QDVNTAVAW) to the C-terminal in rL-A9 (WAVATNVDQ). Modification in the backbone resulted in higher conformational stability of the retro peptide as evident from CD spectra. Molecular docking analysis revealed a higher HER2 binding affinity of [Lu]Lu-DOTA-rL-A9 than the original radiopeptide [Lu]Lu-DOTA-L-A9.

[Tc]Tc-HYNIC-RM2: A potential SPECT probe targeting GRPR expression in prostate cancers.

Introduction: Elevated density of gastrin releasing peptide receptors (GRPR) in prostate cancer has led to exploration of several radiolabeled peptides for imaging and staging of the disease. The GRPR antagonist peptide RM2 has been successfully conjugated with several chelators and radiolabeled with gallium-68. The goal of this study was to synthesize a Tc-labeled probe and investigate its potential for SPECT imaging of prostate cancer.

A robust lyophilized kit for convenient one-step formulation of [Ga]Ga-DOTA-E-[c(RGDfK)] in hospital radiopharmacy for clinical PET imaging.

The present article describes the development of robust lyophilized kit for convenient formulation of [Ga]Ga-DOTA-E-[c(RGDfK)] (E = glutamic acid, R = arginine, G = glycine, D = aspartic acid, f = phenylalanine, K = lysine) radiopharmaceutical for clinical use in non-invasive monitoring of malignancies overexpressing integrin αβ receptors. Five batches of the kit were prepared with optimized kit contents, all of which showed high Ga-radiolabeling yield (>98%). Pre-clinical evaluation of the [Ga]Ga-radiotracer in SCID mice bearing FTC133 tumour exhibited significant accumulation in the tumor xenograft.