Preclinical research progress in HER2-targeted small-molecule probes for breast cancer.

Breast cancer is a malignant tumor that has the highest morbidity and mortality in women worldwide. Human epidermal growth factor receptor 2 (HER2) is a key driver of breast cancer development. Therefore, accurate assessment of HER2 expression in cancer patients and timely initiation or termination of anti-HER2 treatment are crucial for the prognosis of breast cancer patients. The emergence of radiolabeled molecular probes targeting HER2 makes this assessment possible. This article describes different types of small-molecule probes that target HER2 and are used in current preclinical applications and summarizes their advantages and disadvantages.

Molecular probes targeting HER2 PET/CT and their application in advanced breast cancer.

PURPOSE: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer cases are among the most aggressive breast tumor subtypes. Accurately assessing HER2 expression status is vital to determining whether patients will benefit from targeted anti-HER2 treatment. HER2-targeted positron emission tomography (PET/CT) is noninvasive, enabling the real-time evaluation of breast cancer patient HER2 status with accuracy. METHODS: We summarize the research progress of PET/CT targeting HER2 in breast cancer, focusing on PET/CT molecular probes targeting HER2 and their clinical application in the management of advanced breast cancer. RESULTS: At present, a variety of different HER2 targeted molecular probes for PET/CT imaging have been developed, including nucleolin-labeled antibodies, antibody fragments, nanobodies, and peptides of various affinities, among others. HER2-targeted PET/CT can relatively accurately evaluate HER2 expression status in advanced breast cancer patients. It has good performance in the early detection of small HER2-positive lesions, evaluation of HER2 status in lesions that cannot be readily biopsied, evaluation of the heterogeneity of multiple metastases, identification of lesions with altered HER2 status, and evaluation of the efficacy of anti-HER2 drugs. CONCLUSION: HER2-targeted PET/CT offers a promising noninvasive approach for real-time assessment of HER2 status，which can be guide targeted treatment for HER2-positive breast cancer patients. Future prospective clinical studies will be invaluable for fully evaluating the importance of HER2-targeted molecular imaging in the management of breast cancer.

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. On the one hand, the response of acid-sensitive peptide (DVar7) to the acidic tumor microenvironment increased the uptake of liposomes in tumors and prolonged the retention time; on the other hand, the response of acid-sensitive phospholipid (DOPE) to the acidic tumor microenvironment improved the controlled release of DOX in tumors. METHODS: The acid-sensitive peptide DVar7 modified liposomes can be obtained by simple incubation of DSPE-DVar7 with DOX-loaded DOPE liposomes (DOPE-lip@DOX). The tumor targeting of the dual pH-responsive liposome was investigated in vitro and in vivo by near-infrared fluorescence imaging. The tumor therapeutic efficacy of DOPE-DVar7-lip@DOX was evaluated in breast cancer mouse model using the traditional liposome as a control. Moreover, we regulated the tumor microenvironment acidity by injecting glucose to further enhance the therapeutic efficacy of cancer. RESULTS: DVar7 can allosterically insert into the tumor cell membrane in the acidic tumor microenvironment to enhance the tumor uptake of liposomes and prolong the retention time of liposomes in tumor. In addition, the therapeutic efficacy of pH-responsive liposomes can be further enhanced by glucose injection regulating the acidity of tumor microenvironment. DISCUSSION: DVar7 modified acid-sensitive nanocarriers combined with acidity regulation have great potential to improve drug resistance in clinical practice, thus improving the response rate and therapeutic effect of chemotherapy.

18F-FDG PET/CT Findings in a Patient With Neutrophilic Leukemoid Reaction Associated With Multiple Myeloma.

F-FDG PET/CT was performed on a 48-year-old woman with leukocytosis (white blood cell count 57.10 × 10/L, 84.0% neutrophils) and monoclonal gammopathy to investigate the possibility of reactive neutrophilia secondary to plasmacytoma. On the background of skeletal "superscan," the maximum intensity projection image of PET demonstrated the highest metabolic region in the left sacrum, which was confirmed as an osteolytic lesion by CT. Biopsy of the sacral lesion revealed a plasma cell myeloma, indicating the diagnosis of neutrophilic leukemoid reaction associated with multiple myeloma. The white blood cell counts dramatically dropped to the normal level after 1 cycle of chemotherapy for multiple myeloma.

(99m)Tc-HisoDGR as a Potential SPECT Probe for Orthotopic Glioma Detection via Targeting of Integrin α5ß1.

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 αvß3, αvß5, and α5ß1, have generated clinical interest for glioma diagnosis and antitumor therapy. Integrin α5ß1 has been highlighted as a prognostic and diagnostic marker in glioma, and its expression is correlated with a worse prognosis in high-grade glioma. However, unlike extensively studied integrins αvß3 and αvß5, very few integrin α5ß1-specific radiotracers have been reported. Developing α5ß1-specific radiotracers may provide alternative diagnosis and evaluation options in addition to well-studied αvß3/αvß5-specific tracers, and they may add new documents for profiling tumor progression. Here, a novel integrin α5ß1-specific probe (99m)Tc-HisoDGR was fabricated for SPECT (single-photon emission computed tomography) imaging of glioma. To confirm its selective targeting of integrin α5ß1 in vivo, the mouse models of α5ß1-positive U87MG human glioma were subjected to SPECT/CT scans, and biodistribution experiments and blocking studies were performed. Small-animal SPECT/CT imaging experiments demonstrated that the tumors were clearly visualized in both subcutaneous and orthotopic glioma tumor models with clear background at 0.5, 1, and 2 h p.i. The tumor accumulation of (99m)Tc-HisoDGR showed significant reduction when excess cold isoDGR peptide was coinjected, suggesting that the tumor uptake was specifically mediated. Our work revealed that (99m)Tc-HisoDGR represented a powerful molecular probe for integrin α5ß1-positive cancer imaging; moreover, it might be a promising tool for evaluating malignancy, predicting prognosis, selecting subpopulations of patients who might be sensitive to integrin α5ß1-targeted drugs, and assessing and monitoring the response to integrin α5ß1-targeted drugs in clinical trials.