[Tc]Tc-MY6349 Probe for Trop2-Targeted SPECT Imaging: From Preclinical to Pilot Clinical Study.

The trophoblast cell-surface antigen 2 (Trop2) is markedly overexpressed in breast cancers, with a particularly high incidence in triple-negative breast cancer. The therapeutic relevance of Trop2 expression is underscored by the approval of an antibody-drug conjugate for triple-negative breast cancer treatment. However, there is no a predictive technique for accurate whole-body mapping of Trop2 expression in patients.

68Ga-MY6349 PET/CT imaging to assess Trop2 expression in multiple types of cancer.

BACKGROUNDConsidering that trophoblast cell-surface antigen 2 (Trop2) is overexpressed in a wide range of human epithelial cancers, it presents an attractive target for diagnosis and treatment of multiple types of cancer. Herein, we have developed a Trop2-specific radiotracer, 68Ga-MY6349, and present a prospective, investigator-initiated trial to explore the clinical value of 68Ga-MY6349 PET/CT.METHODSIn this translational study, 90 patients with 15 types of cancer who underwent 68Ga-MY6349 PET/CT were enrolled prospectively.

Nuclear imaging of PD-L1 expression promotes the synergistic antitumor efficacy of targeted radionuclide therapy and immune checkpoint blockade.

Purpose: In order to maximize synergistic effect of targeted radionuclide therapy (TRT) and immune checkpoint blockade (ICB) as well as reduce the toxicity, we pioneered a strategy guided by PD-L1-targeted nuclear medicine imaging for the combination of TRT and ICB towards precision cancer therapy.

Methods: As a novel targeted radiotherapeutic agent, Lu-AB-3PRGD targeting integrin αβ was developed to achieve sustained antitumor effect by introducing an albumin binder (AB) into the structure of 3PRGD. The Lu-AB-3PRGD TRT as well as different types of combination therapies of Lu-AB-3PRGD TRT and anti-PD-L1 ICB were performed in animal models.

Implication of Tc-sum IL-2 SPECT/CT in immunotherapy by imaging of tumor-infiltrating T cells.

Background: Although immune checkpoint blockade (ICB) and adoptive T cell transfer (ACT) therapy have achieved impressive clinical outcomes, majority of patients do not respond to immunotherapy. Tumor-infiltrating T cells, a critical factor to immunotherapy, is dynamically changing. Therefore, a reliable real-time in vivo imaging system for tumor-infiltrating T cells, but not immunohistochemical analyses, will be more valuable to predict response and guide immunotherapy.

Molecular imaging of HER2 expression in breast cancer patients using a novel peptide-based tracer Tc-HP-Ark2: a pilot study.

Background: Due to the temporal and spatial heterogeneity of human epidermal growth factor receptor 2 (HER2) expression in breast tumors, immunohistochemistry (IHC) cannot accurately reflect the HER2 status in real time, which may cause misguided treatment decisions. HER2-specific imaging can noninvasively determine HER2 status in primary and metastatic tumors. In this study, HER2 expression in breast cancer patients was determined in vivo by SPECT/CT of Tc-HP-Ark2, comparing with PET/CT of F-FDG lesion by lesion.

Palmitic Acid-Conjugated Radiopharmaceutical for Integrin αβ-Targeted Radionuclide Therapy.

Peptide receptor radionuclide therapy (PRRT) is an emerging approach for patients with unresectable or metastatic tumors. Our previously optimized RGD peptide (3PRGD) has excellent targeting specificity for a variety of integrin αβ/αβ-positive tumors and has been labeled with the therapeutic radionuclide [Lu]LuCl for targeted radiotherapy of tumors. However, the rapid clearance of [Lu]Lu-DOTA-3PRGD (Lu-3PRGD) in vivo requires two doses of 111 MBq/3 mCi to achieve effective tumor suppression, limiting its further clinical application.

SPECT Imaging of Acute Disc Herniation by Targeting Integrin α5β1 in Rat Models.

Objective: Traditional morphological imaging of intervertebral disc herniation (IVDH) is challenging in early disease diagnosis. Aiming at the early diagnosis of IVD by non-invasive molecular imaging targeting of integrin α5β1, we performed novel imaging in rats with acute IVDH for the first time.

Methods: Animal models were prepared by conducting an established needle puncture procedure through the normal intervertebral disc (IVD).

Preclinical evaluation of [Tc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT.

Purpose: Overexpression of epithelial cell adhesion molecule (EpCAM) plays essential roles in tumorigenesis and tumor progression in almost all epithelium-derived cancer. Monitoring EpCAM expression in tumors can be used for the diagnosis, staging, and prognosis of cancer patients, as well as guiding the individualized treatment of EpCAM-targeted drugs. In this study, we described the synthesis and evaluation of a site-specifically [Tc]Tc-labeled EpCAM-targeted nanobody for the SPECT/CT imaging of EpCAM expression.

An efficient method for the site-specific Tc labeling of nanobody.

Recently, there has been a lot of interest by using nanobodies (heavy chain-only antibodies produced naturally from the ) as targeting molecules for molecular imaging, especially for the nuclear medicine imaging. A radiolabeled method that generates a homogeneous product is of utmost importance in radiotracer development for the nuclear medicine imaging. The conventional method for the radiolabeling of nanobodies is non-specifically, which conjugates the radioisotope chelating group to the side chain É›-amine group of lysine or sulfhydryl of cysteine of nanobodies, with a shortcoming of produce of the heterogeneous radiotracer.

An Integrin-αβ/αβ-Bitargeted Probe for the SPECT Imaging of Pancreatic Adenocarcinoma in Preclinical and Primary Clinical Studies.

Pancreatic adenocarcinoma (PA) is one of the deadliest human malignancies. However, early detection, prediction of surgical resectability, and prognosis of PA are challenging with current conventional imaging technologies in the clinic. Molecular imaging technologies combined with novel imaging probes could be useful for early detection and accurate staging of PA.

A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer.

Background: The acidic microenvironment of cancer can promote tumor metastasis and drug resistance. Acidic tumor microenvironment-targeted therapy is currently an important means for treating tumors, inhibiting metastasis, and overcoming drug resistance. In this study, a dual pH-responsive DOX-encapsulated liposome (DOPE-DVar7-lip@DOX) was designed and fabricated for targeting the acidic tumor microenvironment.

Nuclear imaging-guided PD-L1 blockade therapy increases effectiveness of cancer immunotherapy.

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 Tc-MY1523 targeting PD-L1 for the enhanced therapeutic efficacy of PD-L1 blockade immunotherapy by the guidance of Tc-MY1523 SPECT/CT imaging.

Methods: The binding affinity and specificity of nanobody MY1523 were measured in vitro.

Developing PEGylated Reversed D-Peptide as a Novel HER2-Targeted SPECT Imaging Probe for Breast Cancer Detection.

Human epidermal growth factor receptor-2 (HER2)-enriched breast cancer is characterized by strong invasiveness, high recurrence rate, and poor prognosis. HER2-specific imaging can help screening right patients for appropriate HER2-targeted therapies. Previously, we have developed a Tc-labeled HER2-targeted H6 peptide for SPECT imaging of breast cancer.

An Integrin Alpha 6-Targeted Radiotracer with Improved Receptor Binding Affinity and Tumor Uptake.

In this study, we reported a Tc-labeled integrin α-targeted peptide as the molecular imaging probe for tumor imaging by single-photon emission computed tomography (SPECT). We found that replacing Cys-Cys cyclized RWY peptide (sequence: cCRWYDENAC) with lactam-bridged cyclic cKiE peptide (sequence: cKRWYDENAisoE) did not sacrifice the integrin α-binding affinity and specificity of cKiE radiotracer. To further improve the radiotracer's tumor targeting capability, the dimerized cKiE peptide (termed cKiE2) was designed, and the corresponding radiotracer Tc-cKiE2 was evaluated for tumor uptake and in vivo pharmacokinetics properties in tumor models.

A Cu-porphyrin-based dual-modal molecular probe with integrin α β targeting function for tumour imaging.

Pyropheophorbide-a (Pyro) is a promising multifunctional molecule for multimodal tumour imaging and photodynamic therapy, but its clinical applications are seriously restricted by the limited tumour accumulation capability. Here, we designed and synthesized a small-molecule probe that achieved specific dual-modal tumour imaging based on Pyro. Briefly, a novel molecule combining Pyro, an RGD dimer peptide (3PRGD ) and Cu, was designed and synthesized, and the obtained molecule, Cu-Pyro-3PRGD , exhibited high tumour specificity in both positron emission tomography and optical imaging in vivo.

Improved in Vivo Targeting Capability and Pharmacokinetics of Tc-Labeled isoDGR by Dimerization and Albumin-Binding for Glioma Imaging.

Previously, we successfully developed the c(phg-isoDGRk) peptide as a novel integrin αβ-targeted SPECT imaging probe Tc-HisoDGR for Glioma imaging. However, the fast clearance of Tc-HisoDGR in blood reduced its tumor accumulation and retention, which would be the obstacles for further clinical application. Dimerization and albumin-binding strategies have been proven as effective approaches to improve tumor targeting capability and blood circulation time of radiotracers.

Lectin-Mediated pH-Sensitive Doxorubicin Prodrug for Pre-Targeted Chemotherapy of Colorectal Cancer with Enhanced Efficacy and Reduced Side Effects.

Doxorubicin (DOX) has been clinically used as a broad-spectrum chemotherapeutic agent for decades, but its clinical application is hindered by the lack of tumour specificity, severe cardiotoxicity and haematotoxicity. Pre-targeted strategies are highly tumour-specific, therapeutic approaches. Herein, a novel pre-targeted system was constructed, aiming to enhance anticancer efficacy of DOX and maximally reduce its side effects.

(99m)Tc-HisoDGR as a Potential SPECT Probe for Orthotopic Glioma Detection via Targeting of Integrin α5β1.

Integrins, a large family of cell adhesion receptors, have been shown to play an important role for glioma proliferation and invasion. Several integrin receptors, including αvβ3, αvβ5, and α5β1, have generated clinical interest for glioma diagnosis and antitumor therapy. Integrin α5β1 has been highlighted as a prognostic and diagnostic marker in glioma, and its expression is correlated with a worse prognosis in high-grade glioma.