Comparison of PET tracing and biodistribution between Cu-labeled micro-and nano-polystyrene in a murine inhalation model.

Introduction: Recent studies showed the presence of microplastic in human lungs. There remains an unmet need to identify the biodistribution of microplastic after inhalation. In this study, we traced the biodistribution of inhaled micro-sized polystyrene (mPS) and/or nano-sized PS (nPS) using Cu with PET in mice.

Porphyrin-Based Brain Tumor-Targeting Agents: [Cu]Cu-porphyrin and [Cu]Cu-TDAP.

The aim of this study is to evaluate a radioactive metal complex platform for brain tumor targeting. Herein, we introduce a new porphyrin derivative, 5,10,15,20-(tetra-,-dimethyl-4-aminophenyl)porphyrin (TDAP), in which four ,-dimethyl-4--phenylenediamine (DMPD) moieties are conjugated to the porphyrin labeled with the radiometal Cu. DMPD affected the pharmacokinetics of porphyrin in terms of retention time in vivo and tumor-targeting ability relative to those of unmodified porphyrin.

The Prediction of HER2-Targeted Treatment Response Using Cu-Tetra-Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report.

A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status. Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions.

PET Tracing of Biodistribution for Orally Administered Cu-Labeled Polystyrene in Mice.

Plastics are used commonly in the world because of their convenience and cost effectiveness. Microplastics, an environmental threat and human health risk, are widely detected in food and consequently ingested. However, degraded plastics are found everywhere, creating an environmental threat and human health risk.

An Improved At-Labeled Agent for PSMA-Targeted α-Therapy.

α-Particle emitters targeting the prostate-specific membrane antigen (PSMA) proved effective in treating patients with prostate cancer who were unresponsive to the corresponding β-particle therapy. At is an α-emitter that may engender less toxicity than other α-emitting agents. We synthesized a new At-labeled radiotracer targeting PSMA that resulted from the search for a pharmacokinetically optimized agent.

Synthesis and preliminary evaluation of At-labeled inhibitors of prostate-specific membrane antigen for targeted alpha particle therapy of prostate cancer.

Introduction: The high potency and short tissue range of α-particles are attractive features for targeted radionuclide therapy, particularly for cancers with micro-metastases. In the current study, we describe the synthesis of a series of At-labeled prostate-specific membrane antigen (PSMA) inhibitors and their preliminary evaluation as potential agents for metastatic prostate cancer treatment.

Methods: Four novel Glu-urea based PSMA ligands containing a trialkyl stannyl group were synthesized and labeled with At, and for comparative purposes, I, via halodestannylation reactions with N-chlorosuccinimide as the oxidant.

Brush border enzyme-cleavable linkers: Evaluation for reducing renal uptake of radiolabeled prostate-specific membrane antigen inhibitors.

Introduction: Radiolabeled, low-molecular-weight prostate-specific membrane antigen (PSMA) inhibitors based on the Glu-ureido pharmacophore show promise for the detection and treatment of castration-resistant prostate cancer; however, high renal retention of activity, related in part to overexpression of PSMA in kidneys can be problematic. The goal of the current study was to investigate the use of brush border enzyme-cleavable linkers as a strategy for reducing kidney activity levels from radiolabeled PSMA inhibitors.

Methods: PSMA-769 (6), a derivative of the prototypical PSMA inhibitor (((S)‑1‑carboxy‑5‑(4‑iodobenzamido)pentyl)carbamoyl)glutamate (12) modified to contain a Gly-Tyr linker, and its protected tin precursor (11) were synthesized starting from the basic pharmacophore molecule Lys-urea-Glu.

d-Amino Acid Peptide Residualizing Agents for Protein Radioiodination: Effect of Aspartate for Glutamate Substitution.

The residualizing prosthetic agent -(3-[I]iodobenzoyl)-Lys⁵--maleimido-Gly¹-d-GEEEK ([I]IB-Mal-d-GEEEK) showed promise for the radioiodination of monoclonal antibodies (mAbs) that bind to internalizing molecular targets. Although enhanced tumor uptake was achieved in these studies, elevated kidney accumulation also was observed, particularly with low-molecular-weight, single-domain antibody fragments (sdAbs). Here, we developed an analogous agent (IB-Mal-d-GDDDK), in which glutamate residues (E) were replaced with aspartates (D) to determine whether this modification could decrease renal uptake.

Astatine-211 labeled anti-HER2 5F7 single domain antibody fragment conjugates: radiolabeling and preliminary evaluation.

Introduction: Derived from heavy chain only camelid antibodies, ~15-kDa single-domain antibody fragments (sdAbs) are an attractive platform for developing molecularly specific imaging probes and targeted radiotherapeutics. The rapid tumor accumulation and normal tissue clearance of sdAbs might be ideal for use with At, a 7.2-h half-life α-emitter, if appropriate labeling chemistry can be devised to trap At in cancer cells after sdAb binding.

Fluorine-18 Labeling of the HER2-Targeting Single-Domain Antibody 2Rs15d Using a Residualizing Label and Preclinical Evaluation.

Purpose: Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts.

Catabolism of (64)Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model.

Human serum albumin (HSA), the most abundant protein in blood plasma, has been used as a drug carrier for the last few decades. Residualizingly radiolabeled serum albumin has been reported to be avidly taken up by tumors of sarcoma-bearing mice and to most likely undergo lysosomal degradation. In this study, we prepared (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N'″-tetraacetic acid (DOTA) and Cy5.

Hybrid PET/optical imaging of integrin αVβ3 receptor expression using a (64)Cu-labeled streptavidin/biotin-based dimeric RGD peptide.

Background: Hybrid PET/optical imaging provides quantitative and complementary information for diagnosis of tumors. Herein, we developed a (64)Cu-labeled AlexaFluor 680-streptavidin ((AF)SAv)/biotin-based dimeric cyclic RGD peptide (RGD2) for hybrid PET/optical imaging of integrin αVβ3 expression.

Methods: (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-(AF)SAv/biotin-PEG-RGD2 was prepared by formation of a complex comprising DOTA-(AF)SAv and biotin-PEG-RGD2, followed by radiolabeling with (64)Cu.

Hybrid lymph node imaging using 64Cu-labeled mannose-conjugated human serum albumin with and without indocyanine green.

Objective: Human serum albumin (HSA), which has 58 Lys residues, one Cys residue, and indocyanine green (ICG) adsorption sites, can be used as a multifunctional platform for the development of hybrid imaging probes. In this study, we prepared 64Cu-labeled mannose-conjugated HSA with and without ICG ([64Cu]1-ICG and [64Cu]1, respectively) and compared hybrid PET/near-infrared fluorescence (NIRF) imaging with positron emission tomography (PET)/Cerenkov luminescence (CL) imaging of lymph nodes (LNs).

Materials And Methods: 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)/mannose-conjugated HSA (1) was synthesized by conjugating mannose molecules to Lys residues and a DOTA molecule to a Cys residue of HSA.

Tumor-homing glycol chitosan-based optical/PET dual imaging nanoprobe for cancer diagnosis.

Imaging techniques including computed tomography, magnetic resonance imaging, and positron emission tomography (PET) offer many potential benefits to diagnosis and treatment of cancers. Each method has its own strong and weak points. Therefore, multimodal imaging techniques have been highlighted as an alternative method for overcoming the limitations of each respective imaging method.

Characterization of oleanolic acid derivative for colon cancer targeting with positron emission tomography.

Oleanolic acid (OA) is a pentacyclic triterpenoid found in various plant species. Triterpenoid compounds have been shown to inhibit tumor proliferation and to induce apoptosis in cancer cells. We synthesized an OA derivative and evaluated its inhibitory effects on cell proliferation in human colon cancer.

⁶⁸Ga-NODAGA-VEGF₁₂₁ for in vivo imaging of VEGF receptor expression.

Purpose: Vascular endothelial growth factor (VEGF) is a crucial regulator of angiogenesis. In this study, we labeled VEGF₁₂₁ with (68)Ga using a hydrophilic chelating agent, NODAGA and evaluated the resulting (68)Ga-NODAGA-VEGF₁₂₁ for in vivo imaging of VEGF receptor (VEGFR) expression.

Methods: NODAGA-VEGF₁₂₁ was prepared and its binding affinity for VEGFR2 was measured using (125)I-VEGF₁₂₁.

64Cu-Labeled tetraiodothyroacetic acid-conjugated liposomes for PET imaging of tumor angiogenesis.

Introduction: We synthesized and evaluated (64)Cu-labeled tetraiodothyroacetic acid (tetrac)-conjugated liposomes for PET imaging of tumor angiogenesis, because tetrac inhibits angiogenesis via integrin αVβ3.

Methods: Tetrac-PEG-DSPE and DOTA-PEG-DSPE were synthesized and formulated with other lipids into liposomes. The resulting tetrac/DOTA-liposomes were labeled with (64)Cu at 40 °C for 1 h and purified using a PD-10 column.

Cholesteryl hyaluronic acid-coated, reduced graphene oxide nanosheets for anti-cancer drug delivery.

Here, we report hyaluronyl reduced graphene oxide (rGO) nanosheets as a tumor-targeting delivery system for anticancer agents. Hyaluronyl-modified rGO nanosheets were prepared by synthesizing cholesteryl hyaluronic acid (CHA) and using it to coat rGO nanosheets, yielding CHA-rGO. Compared with rGO, CHA-rGO nanosheets showed increased colloidal stability under physiological conditions and improved in vivo safety, with a survival rate of 100% after intravenous administration of 40 mg/kg in mice.

A vascular endothelial growth factor 121 (VEGF(121))-based dual PET/optical probe for in vivo imaging of VEGF receptor expression.

We have developed a vascular endothelial growth factor 121 (VEGF121)-based, dual positron emission tomography (PET)/optical imaging probe for monitoring VEGF receptor (VEGFR) expression using a streptavidin (SAv)-biotin platform. (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N'″-tetraacetic acid (DOTA)-conjugated Alexa Fluor 680 (AF)-SAv/biotin-PEG-VEGF121 ((64)Cu-labeled dual probe) was prepared with a radiochemical yield of 31.40 ± 3.

Facile method to radiolabel glycol chitosan nanoparticles with (64)Cu via copper-free click chemistry for MicroPET imaging.

An efficient and straightforward method for radiolabeling nanoparticles is urgently needed to understand the in vivo biodistribution of nanoparticles. Herein, we investigated a facile and highly efficient strategy to prepare radiolabeled glycol chitosan nanoparticles with (64)Cu via a strain-promoted azide-alkyne cycloaddition strategy, which is often referred to as click chemistry. First, the azide (N3) group, which allows for the preparation of radiolabeled nanoparticles by copper-free click chemistry, was incorporated to glycol chitosan nanoparticles (CNPs).

In vivo characterization of 68Ga-NOTA-VEGF 121 for the imaging of VEGF receptor expression in U87MG tumor xenograft models.

Purpose: Vascular endothelial growth factor receptors (VEGFRs) are associated with tumor growth and induction of tumor angiogenesis and are known to be overexpressed in various human tumors. In the present study, we prepared and evaluated (68)Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid-benzyl (NOTA)-VEGF(121) as a positron emission tomography (PET) radioligand for the in vivo imaging of VEGFR expression.

Methods: (68)Ga-NOTA-VEGF(121) was prepared by conjugation of VEGF(121) and p-SCN-NOTA, followed by radiolabeling with (68)GaCl(3) and then purification using a PD-10 column.

Evaluation of the angiogenesis inhibitor KR-31831 in SKOV-3 tumor-bearing mice using (64)Cu-DOTA-VEGF(121) and microPET.

KR-31831 ((2R,3R,4S)-6-amino-4-[N-(4-chloropheyl)-N-(1H-imidazol-2ylmethyl)amino]-3-hydroxyl-2-methyl-2-dimethoxymethyl-3,4-dihydro-2H-1-benzopyran), an angiogenesis inhibitor, was evaluated in tumor-bearing mice using molecular imaging technology. Pre-treatment microPET images were acquired on SKOV-3 cell-implanted nude mice after injection with (64)Cu-DOTA-VEGF(121). KR-31831 (50 mg/kg) was then injected intraperitoneally into the treatment group (n=3), while injection vehicle was injected into the control (n=4) and blocking (n=3) groups.

Development of target-specific multimodality imaging agent by using hollow manganese oxide nanoparticles as a platform.

A platform protocol developed based on the hollow manganese oxide nanoparticles provided multimodal diagnostic agents, which allow the selectively detect vulva cancer with T(1)-weighted in vivo MRI.

Toxicological evaluation of realistic emission source aerosols (TERESA): introduction and overview.

Determining the health impacts of sources and components of fine particulate matter (PM(2.5)) is an important scientific goal. PM(2.