Abstract While IL-2 can potently activate both NK and T cells, its short in vivo half-life, severe toxicity, propensity to amplify Treg cells are major barriers that prevent from being widely used for cancer therapy. In this study, we construct a recombinant immunocytokine comprising tumor-targeting antibody (Ab) super mutant (sumIL-2) with decreased CD25 binding increased CD122 binding. The Ab-sumIL2 significantly enhances antitumor activity through tumor targeting specific cytotoxic...

This report describes the synthesis of two cyclic RGD (Arg-Gly-Asp) conjugates, HYNIC-2PEG4-dimer (HYNIC = 6-hydrazinonicotinyl; 2PEG4-dimer E[PEG4-c(RGDfK)]2; and PEG4 15-amino-4,7,10,13-tetraoxapentadecanoic acid) HYNIC-3PEG4-dimer (3PEG4-dimer PEG4-E[PEG4-c(RGDfK)]2), evaluation their 99mTc complexes [99mTc(HYNIC-2PEG4-dimer)(tricine)(TPPTS)] (99mTc-2PEG4-dimer: TPPTS trisodium triphenylphosphine-3,3′,3′′-trisulfonate) [99mTc(HYNIC-3PEG4-dimer)(tricine)(TPPTS)] (99mTc-3PEG4-dimer) as...

PET friendly: Labels for imaging are incorporated into completely organic porphysomes by using a fast (30 min), one-pot, high-yielding (>95 %) procedure to produce highly stable (>48 h) radiolabeled nanoparticles that show the highest specific activity ever reported 64Cu-labeled nanoparticle. These 64Cu-porphysomes can be accurately and noninvasively tracked in vivo. Detailed facts of importance specialist readers published as "Supporting Information". Such documents peer-reviewed, but not...

Porphyrin based photosensitizers are useful agents for photodynamic therapy (PDT) and fluorescence imaging of cancer. Porphyrins also excellent metal chelators forming highly stable metallo-complexes making them efficient delivery vehicles radioisotopes. Here we investigated the possibility incorporating (64)Cu into a porphyrin-peptide-folate (PPF) probe developed previously as folate receptor (FR) targeted fluorescent/PDT agent, evaluated potential turning resulting (64)Cu-PPF positron...

^99mTc-3PRGD2 is a new SPECT tracer targeting integrin α_Vβ₃ receptor for detecting tumors, imaging angiogenesis, and evaluating tumor response to therapy. A multicenter study was designed investigate the efficacy of evaluation patients with lung cancer. <b>Methods:</b> Seventy (51 men, 19 women; mean age ± SD, 63 9 y) suspected lesion whom definite pathologic diagnosis finally obtained (malignant, <i>n</i> = 58; benign, 12) were recruited from 6 centers....

Hypoxia is a hostile hallmark of most solid tumors, which often leads to multidrug resistance (MDR) and causes the failure chemotherapy. also promotes epithelial–mesenchymal transition (EMT), leading acceleration tumor metastasis. Many chemotherapeutic drugs can further exacerbate hypoxia thus promote Therefore, relieving necessary for chemotherapy inhibit both MDR EMT. Herein, highly stable cerasomal perfluorocarbon nanodroplets with an atomic layer polyorganosiloxane surface pH-sensitive...

Abstract Since the discovery of metal nanoparticles (NPs) in 1960s, unknown toxicity, cost and ethical hurdles research humans have hindered translation these NPs to clinical use. In this work, we demonstrate that Pt with protein coronas are generated vivo human blood when a patient is treated cisplatin. These self-assembled form rapidly, accumulate tumors, remain body for an extended period time. Additionally, safe use can act as anti-cancer agents inhibit chemotherapy-resistant tumor...

Radiolabeled cyclic RGD (Arg-Gly-Asp) peptides represent a new class of radiotracers with potential for early tumor detection and noninvasive monitoring metastasis therapeutic response in cancer patients. This article describes the synthesis two peptide dimer conjugates, DOTA-PEG(4)-E[PEG(4)-c(RGDfK)](2) (DOTA-3PEG(4)-dimer: DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; PEG(4) 15-amino-4,7,10,13-tetraoxapentadecanoic acid) DOTA-G(3)-E[G(3)-c(RGDfK)](2) (DOTA-3G(3)-dimer:...

This report describes the synthesis of two new cyclic RGD (Arg-Gly-Asp) dimers, 3 (E[G(3)-c(RGDfK)](2)) and 4 (G(3)-E[G(3)-c(RGDfK)](2)), their corresponding conjugates 5 (HYNIC-E[G(3)-c(RGDfK)](2): HYNIC = 6-(2-(2-sulfonatobenzaldehyde)hydrazono)nicotinyl) 6 (HYNIC-G(3)-E[G(3)-c(RGDfK)](2)). Integrin alpha(v)beta(3) binding affinities were determined by displacement (125)I-echistatin bound to U87MG glioma cells. (99)(m)Tc complexes 7 ([(99m)Tc(5)(tricine)(TPPTS)]: TPPTS trisodium...

Gadolinium (Gd3+)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient radiosensitization efficacy. Little attention has been given using nanovesicles improve its Herein, Gd-Tex transformed into building blocks "Gd-Tex-lipids" self-assemble called Gd-nanotexaphyrins (Gd-NTs), realizing high density packing of in single nanovesicle and achieving accumulation tumors. To elucidate the impact O2...

A novel dual-modality molecular probe composed of biocompatible Fe(3)O(4) nanocrystal, monoclonal antibody and radionuclide was designed prepared. All functional components in the probe, i.e., Fe(3)O(4), PEG, mAb 3H11 (125)I, were chemically bonded together for forming a stable probe. Systematic vitro experiments carried out evaluating biological activity targeting series vivo performed based on imaging detecting xenografted tumors nude mice by MRI gamma-imaging techniques. The...

This report describes the biologic evaluations of [ 99m Tc(HYNIC-3P-RGD 2 )(tricine)(TPPTS)] ( Tc-3P-RGD : 6-hydrazinonicotinyl; 3P-RGD = PEG 4 -E[PEG -c(RGDfK)] ; 15-amino-4,7,10,13-tetraoxapentadecanoic acid; and TPPTS trisodium triphenylpho-sphine-3,3′,3“-trisulfonate), Tc(HYNIC-3G-RGD Tc-3G-RGD 3G-RGD G 3 -E[G Gly-Gly-Gly), TcO(MAG −3G-RGD ) (MAG mercaptoacetylglycylglycyl) as radiotracers for noninvasive imaging tumor integrin α v β expression in five xenografted tumor-bearing models....

Integrin αvβ3 is overexpressed in both neovasculature and glioma cells. We aimed to evaluate (68)gallium-BNOTA-PRGD2 ((68)Ga-PRGD2) as a new reagent for noninvasive integrin imaging patients. With informed consent, 12 patients with suspicious brain glioma, diagnosed by enhanced magnetic resonance (MRI) scanning, were enrolled undergo (68)Ga-PRGD2 PET/CT (18)F-FDG scans before surgery. The preoperative images compared correlated the pathologically determined WHO grade. Next, expression of...

Objectives Strategies to improve the responsiveness of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockade therapy remain an essential topic in cancer immunotherapy. In this study, we developed a new radiolabeled nanobody-based imaging probe 99m Tc-MY1523 targeting PD-L1 for enhanced therapeutic efficacy immunotherapy by guidance SPECT/CT imaging. Methods The binding affinity and specificity nanobody MY1523 were measured vitro. was with Tc site-specific...

Abstract Targeting receptors overexpressed on cancer cells with radiolabeled peptides has become a crucial aspect of molecular imaging in oncology. Small offer favorable characteristics for tumor targeting minimal side effects and toxicity owing to their small size simple radiolabeling protocols. Among them, somatostatin analogs have received regulatory approval the diagnosis treatment neuroendocrine tumors. Cyclic RGD (Arg‐Gly‐Asp) peptides, bombesin analogs, glucagon‐like peptide‐1 are...

The trophoblast cell-surface antigen 2 (Trop2) is markedly overexpressed in breast cancers, with a particularly high incidence triple-negative cancer. therapeutic relevance of Trop2 expression underscored by the approval an antibody-drug conjugate for cancer treatment. However, there no predictive technique accurate whole-body mapping patients. In this study, we developed novel Trop2-specific molecular probe, [99mTc]Tc-MY6349, and evaluated its safety feasibility detecting using SPECT/CT...

To predict the epidermal growth factor receptor (EGFR) T790M status of patients with advanced non-small cell lung cancer (NSCLC) following first-line first-/second-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy, related clinical features and chest computed tomography (CT) images NSCLC in our hospital were retrospectively collected. All who met criteria randomly divided into training validation cohorts. Then, a model filtered characteristics deep-learning (DLM) constructed. The...

Integrin αvβ3 has been well-documented as one of the key players in process tumor angiogenesis. Radiolabeled RGD (Arg-Gly-Asp) peptides that specifically target integrin have great potential for early detection and noninvasively monitoring status We developed a cyclic dimeric probe 99mTc-HYNIC-Gly3-E[PEG4-c(RGDfK)]2 (99mTc-G3-2P4-RGD2) (using tricine TPPTS coligands, = trisodium triphenylphosphine-3,3′,3′′-trisulfonate), investigated whether it could be used to visualize quantify expression...

This report presents the synthesis and evaluation of 111In(DOTA-6G-RGD4) (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid; 6G-RGD4 E{G3-E[G3-c(RGDfK)]2}2 G3 Gly-Gly-Gly), 111In(DOTA-RGD4) (RGD4 E{E[c(RGDfK)]2}2) 111In(DOTA-3G-RGD2) (3G-RGD2 G3-E[G3-c(RGDfK)]2) as new radiotracers for imaging integrin αvβ3-positive tumors. The IC50 values DOTA-6G-RGD4, DOTA-RGD4, DOTA-3G-RGD2 were determined to be 0.4 ± 0.1, 1.4 0.1 1.1 nM against 125I-c(RGDyK) bound U87MG human glioma cells....

The purpose of this study was to demonstrate the valence cyclic RGD peptides, P-RGD (PEG(4)-c(RGDfK): PEG(4) = 15-amino-4,710,13-tetraoxapentadecanoic acid), P-RGD(2) (PEG(4)-E[c(RGDfK)](2), 2P-RGD(4) (E{PEG(4)-E[c(RGDfK)](2)}(2), 2P4G-RGD(4) (E{PEG(4)-E[G(3)-c(RGDfK)](2)}(2): G(3) Gly-Gly-Gly) and 6P-RGD(4) (E{PEG(4)-E[PEG(4)-c(RGDfK)](2)}(2)) in binding integrin α(v)β(3), assess impact peptide linker multiplicity on biodistribution properties, excretion kinetics metabolic stability their...

Integrin α_vβ₆, a member of the integrin family, is specifically expressed in many malignancies but not normal organs. Overexpression α_vβ₆ usually correlated with malignant potential and poor prognosis. In this study, we describe synthesis evaluation ^99mTc-labeled α_vβ₆–targeting peptide as SPECT radiotracer for vivo imaging expression. <b>Methods:</b> An (denoted HK peptide) was conjugated 6-hydrazinonicotinyl...

This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG2000-DOTA), followed chelating radioisotope 177Lu. Its applications in optical and nuclear imaging tumor uptake biodistribution, as well photothermal killing cancer cells, were investigated. It was found that...