Phase I study of [Ga]Ga-HX01 for targeting integrin αvβ3 and CD13 in healthy and malignancy subjects.

Purpose: Noninvasive angiogenesis visualization is essential for evaluating tumor proliferation, progression, invasion, and metastasis. This study aimed to translate the heterodimeric PET tracer [Ga]Ga-HX01, which targets integrin αvβ3 and CD13 in neovascularization, into phase I clinical study.

Methods: This study enrolled 12 healthy volunteers (phase Ia) and 10 patients with malignant tumors (phase Ib).

Development and evaluation of albumin binder-conjugated heterodimeric radiopharmaceuticals targeting integrin αβ and CD13 for cancer therapy.

Purpose: The advancement of heterodimeric tracers, renowned for their high sensitivity, marks a significant trend in the development of radiotracers for cancer diagnosis. Our prior work on [Ga]Ga-HX01, a heterodimeric tracer targeting CD13 and integrin αβ, led to its approval for phase I clinical trials by the China National Medical Production Administration (NMPA). However, its fast clearance and limited tumor retention pose challenges for broader clinical application in cancer treatment.

F-Radiolabeling and Evaluation of an AMD3465 Derivative for PET Imaging of CXCR4 in a Mouse Breast Tumor Model.

The exploration of pharmaceutically active agents and positron emission tomography (PET) tracers targeting CXCR4 has been a focal point in cancer research given its pivotal role in the development and progression of various cancers. While significant strides have been made in PET imaging with radiometal-labeled tracers, the landscape of F-labeled small molecule tracers remains relatively limited. Herein, we introduce a novel and promising derivative, [F]SFB-AMD3465, as a targeted PET tracer for CXCR4.

Risk factors for lateral pelvic lymph node metastasis in patients with lower rectal cancer: a systematic review and meta-analysis.

Background And Objective: Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence (LR) in patients with rectal cancer (RC). The evaluation criteria of lateral lymph node dissection (LLND) for patients in eastern (mainly in Japan) and western countries have been controversial. The aim of this study was to analyse the risk factors for LPLN metastasis in order to guide surgical methods.

Preclinical evaluation of a dual-receptor targeted tracer [Ga]Ga-HX01 in 10 different subcutaneous and orthotopic tumor models.

Purpose: The integrin αβ and aminopeptidase N (APN/CD13) play vital roles in the tumor angiogenesis process. They are highly expressed in a variety of tumor cells and proliferating endothelial cells during angiogenesis, which have been considered as highly promising targets for tumor imaging. Arginine-glycine-aspartic (RGD) and asparagine-glycine-arginine (NGR) are two peptides specifically binding to the integrin αβ and CD13, respectively.

Evaluation of a CD13 and Integrin αβ Dual-Receptor Targeted Tracer Ga-NGR-RGD for Ovarian Tumor Imaging: Comparison With F-FDG.

Ovarian cancer has the highest mortality rate of gynecologic malignancy. F-FDG positron emission tomography (PET) adds an important superiority over traditional anatomic imaging modalities in oncological imaging but has drawbacks including false negative results at the early stage of ovarian cancer, and false positives when inflammatory comorbidities are present. Aminopeptidase N (APN, also known as CD13) and integrin αβ are two important targets overexpressed on tumor neo-vessels and frequently on ovarian cancerous cells.

Heterodimeric RGD-NGR PET Tracer for the Early Detection of Pancreatic Cancer.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal gastrointestinal cancer, and its poor prognosis is highly associated with the lack of an efficient early detection technology. Here, we report that RGD-NGR heterodimer labeled with PET isotope could be applied in PDAC early detection.

Procedures: The RGD-NGR tracer was first compared with its corresponding monomeric counterparts via PET imaging studies using mice bearing a subcutaneous BxPC3 tumor.

PET Imaging of CD8 via SMART for Monitoring the Immunotherapy Response.

Imaging of CD8 receptors on T-cells by positron emission tomography (PET) has been considered a promising strategy for monitoring the treatment response to immunotherapy. In this study, a trial of imaging CD8 with our newly developed sequential multiple-agent receptor targeting (SMART) technology was conducted. Mice bearing a subcutaneous colorectal CT26 tumor received three times different immunotherapy treatments (PD1 or CTLA4 or combined).

Thermally sensitive fluorescence imaging system for radiofrequency ablation guidance.

Radiofrequency ablation (RFA) has been clinically used as a minimally invasive procedure for the treatment of many solid tumors. However, the current imaging techniques have some shortages in RFA guidance, especially for the assessment of the margin of ablation. Herein, we developed a novel optical imaging platform to guide RFA utilizing fluorescence resonance energy transfer from a thermally sensitive fluorescent protein conjugated to a near-infrared fluorescent dye.

Photo-Click-Facilitated Screening Platform for the Development of Hetero-Bivalent Agents with High Potency.

A novel photo-click-based platform has been developed for rapid screening and affinity optimization of heterobivalent agents. This method allows for the efficient selection of high-affinity dual receptor-targeting agents streamlining tedious organic synthesis and biological evaluation procedures required by traditional approaches. The high-avidity heterobivalent agents targeting both integrin αβ and urokinase-type plasminogen activator receptors have been developed using this photo-click-facilitated screening platform.

Evaluation of an Integrin αβ and Aminopeptidase N Dual-Receptor Targeting Tracer for Breast Cancer Imaging.

Integrin αβ and aminopeptidase N (APN, also known as CD13) are two important targets involved in the regulation of angiogenesis, tumor proliferation, invasion, and metastasis. In this study, we developed a heterodimeric tracer consisting of arginine-glycine-aspartic (RGD) and asparagine-glycine-arginine (NGR) peptides targeting αβ and CD13, respectively, for PET imaging of breast cancer. The NGR peptide was first modified with N-NOB and then conjugated to BCN-PEG-c(RGDyK) via copper-free click chemistry.

Comparison of AlF- and Ga-labeled NOTA-PEG-LLP2A for PET imaging of very late antigen-4 in melanoma.

Malignant melanoma is an aggressive cancer with poor prognosis. Very late antigen-4 (VLA-4) is overexpressed in melanoma and many other tumors, making it an attractive target for developing molecular diagnostic and therapeutic agents. We compared AlF- and Ga-labeled LLP2A peptides for PET imaging of VLA-4 expression in melanoma.

Cu-Labeled Ubiquitin for PET Imaging of CXCR4 Expression in Mouse Breast Tumor.

Ubiquitin has been recently identified as a chemokine receptor 4 (CXCR4) natural ligand, offering great potential for positron emission computed tomography (PET) imaging of CXCR4 expression. This study reports the preparation and evaluation of (Cu)-radiolabeled ubiquitin for CXCR4 imaging. The ubiquitin was first fused with a C-terminal GGCGG sequence, and the resulting recombinant ubiquitin derivative UbCG4 was then functionalized with the -cyclooctene (TCO) moiety via thiol-maleimide click reaction, followed by Cu-radiolabeling through the TCO/Tz (tetrazine)-based Diels-Alder click reaction.

Synthesis and Evaluation of New Bifunctional Chelators with Phosphonic Acid Arms for Gallium-68 Based PET Imaging in Melanoma.

Due to the increasing use of generator-produced radiometal Gallium-68 (Ga) in positron-emission tomography/computed tomography (PET/CT), reliable bifunctional chelators that can efficiently incorporate Ga into biomolecules are highly desirable. In this study, we synthesized two new bifunctional chelators bearing one or two phosphonic acid functional groups, named p-SCN-PhPr-NE2A1P and p-SCN-PhPr-NE2P1A, with the aim of enabling facile production of Ga-based radiopharmaceuticals. Both chelators were successfully conjugated to LLP2A-PEG, a very late antigen-4 (VLA-4) targeting peptidomimetic ligand, to evaluate their application in Ga-based PET imaging.

Assessment of delayed graft function using susceptibility-weighted imaging in the early period after kidney transplantation: a feasibility study.

Purpose: This study aimed to explore the feasibility of susceptibility-weighted imaging (SWI) for evaluating delayed graft function (DGF) during the early posttransplantation period.

Methods: Sixty-nine recipients who accepted allograft renal transplantation underwent SWI during the second posttransplantation week. Renal allograft function was estimated via the glomerular filtration rate.

A multi-functional polymeric carrier for simultaneous positron emission tomography imaging and combination therapy.

Unlabelled: Multifunctional nanoplatforms offering simultaneous imaging and therapeutic functions have been recognized as a highly promising strategy for personalized nanomedicine. In this work, we synthesized a farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) based triblock copolymer POEG-b-PVBA-b-PFTS (POVF) composed of a poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic block, a poly(FTS) hydrophobic block, and a poly(4-vinylbenzyl azide) (PVBA) middle block. The POVF polymer itself was active in inhibiting the tumor growth in vitro and in vivo.

Cu-Labeled Phosphonate Cross-Bridged Chelator Conjugates of c(RGDyK) for PET/CT Imaging of Osteolytic Bone Metastases.

Objective: The goal of this research was to evaluate c(RGDyK) conjugated to phosphonate-based cross-bridged chelators using Cu-free click chemistry in the 4T1 mouse mammary tumor bone metastasis model in comparison with Cu-CB-TE2A-c(RGDyK), which previously showed selective binding to integrin αvβ3 on osteoclasts.

Experimental: Two phosphonate-based cross-bridged chelators (CB-TE1A1P and CB-TE1K1P) were conjugated to c(RGDyK) through bio-orthogonal strain-promoted alkyne-azide cycloaddition. In vitro and in vivo evaluation of the Cu-labeled TE1A1P-DBCO-c(RGDyK) (AP-c(RGDyK)), TE1K1P-PEG4-DBCO-c(RGDyK) (KP-c(RGDyK)), and CB-TE2A-c(RGDyK) were compared in the 4T1 mouse model of bone metastasis.

Fat status detection and histotypes differentiation in solid renal masses using Dixon technique.

Purpose: To detect fat status and differentiate histotypes of renal masses by using Dixon technique.

Materials And Methods: This study included 134 solid renal masses. Signal intensity index (SII) and fat fraction (FF) in different histotypes were compared.

Dual-Targeted Molecular Imaging of Cancer.

Molecular imaging is critical to personalized and precision medicine. Although singly targeted imaging probes are making an impact both clinically and preclinically, molecular imaging strategies using bispecific probes have enabled improved visualization of cancer in recent years through synergistic targeting of two ligands. In this Focus on Molecular Imaging review, we outline how peptide-, antibody-, and nanoparticle-based platforms have affected this emerging strategy, providing examples and pointing out areas in which the greatest clinical impact may be realized.

JTC801 Induces pH-dependent Death Specifically in Cancer Cells and Slows Growth of Tumors in Mice.

Background & Aims: Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice.

Preclinical immunoPET/CT imaging using Zr-89-labeled anti-PD-L1 monoclonal antibody for assessing radiation-induced PD-L1 upregulation in head and neck cancer and melanoma.

Radiation therapy (RT) can induce upregulation of programmed death ligand 1 (PD-L1) on tumor cells or myeloid cells, which may affect response to PD-1-based immunotherapy. PD-L1 upregulation during RT is a dynamic process that has been difficult to monitor during treatment. The aim of this study was to evaluate the RT-induced PD-L1 upregulation in the tumor and its microenvironment using immunoPET/CT imaging of two syngeneic murine tumor models (HPV+ head and neck squamous cell carcinoma (HNSCC) or B16F10 melanoma).

Targeted Yttrium 89-Doxorubicin Drug-Eluting Bead-A Safety and Feasibility Pilot Study in a Rabbit Liver Cancer Model.

The purpose of this article is to evaluate feasibility and safety of the cancer targeting (radio)-chemoembolization drug-eluting bead (TRCE-DEB) concept drug SW43-DOX-L-NETA(Y) DEB for the intra-arterial treatment of VX2 rabbit liver tumors. The treatment compound comprises of the sigma-2 receptor ligand SW43 for cancer targeting, doxorubicin (DOX), and yttrium (Y) as nonradioactive surrogate for therapeutic (yttrium-90, lutetium-177) and imaging (yttrium-86) radioisotopes via the chelator L-NETA. Ten New Zealand white rabbits with VX2 tumor allografts were used.

In vitro biologic efficacy of sunitinib drug-eluting beads on human colorectal and hepatocellular carcinoma-A pilot study.

Purpose: Sunitinib drug eluting beads (DEB) are a novel anti-angiogenic bead preparation for use in transarterial chemoembolization. However, systematic studies of sunitinib DEB's effect on cancer cells have not been reported. Herein, we assess their direct biologic efficacy against carcinoma cell lines and correlate cell viability with drug release in vitro.