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Erb‐b2 receptor tyrosine kinase 2 (ERBB2; also known as HER2) expression is observed in 25–40% of head and neck squamous cell carcinomas (HNSCC), yet there are no anti‐HER2 therapies under evaluation for HNSCC, as conventional cytostatic anti‐HER2 antibodies have had limited effectiveness and levels of HER2 overexpression are lower in HNSCC tumors compared to breast cancer. Trastuzumab‐deruxtecan (T‐DXd; Enhertu) is a HER2‐targeting antibody‐drug conjugate (ADC) comprising an anti‐HER2 monoclonal antibody, a cleavable linker, and a potent topoisomerase I inhibitor payload, and has shown promising results in very low HER2‐expressing tumors. We compare the efficacy of T‐DXd, trastuzumab‐emtansine (ADC comprising an anti‐HER2 antibody and microtubule inhibitor, T‐DM1; Kadcyla) and trastuzumab (Herceptin) therapy in HNSCC with low and absent HER2 expression in vitro and in vivo. In vitro treatment of a low HER2‐expressing human HNSCC cell line (FaDu) with T‐DXd resulted in dose‐dependent cell death (IC50 values of 9856 ng·mL−1). T‐DXd treatment of FaDu and UMSCC‐47 (low HER2‐expressing cell line) mouse xenografts displayed antitumor activity (P = 0.0001 and 0.015 respectively). When comparing T‐DXd to other approved anti‐HER2 therapies, only FaDu mice treated with T‐DXd showed a reduction in tumor growth (P = 0.0012). In UMSCC‐1 cells (absent HER2 expression), the drug failed to accumulate in tumors and showed no measurable antitumor effect, in contrast to FaDu xenografts, where drug accumulation in the tumor correlated with a therapeutic response. T‐DXd treatment yielded antitumor activity in FaDu and UMSCC‐47 tumors, highlighting the potential for T‐DXd efficacy in low HER2‐expressing tumors. Trastuzumab‐deruxtecan, a HER2‐targeting antibody‐drug conjugate, shows promising antitumor activity in head and neck squamous cell carcinoma with low HER2 expression. In vitro and in vivo studies demonstrated dose‐dependent cell death and tumor growth reduction in low HER2‐expressing cell lines, which correlated with drug accumulation measured using a fluorescent antibody‐drug conjugate.

Twenty novel Mn, Fe, and Cu complexes of ethylene cross-bridged tetraazamacrocycles with potentially copolymerizable allyl and benzyl pendant arms were synthesized and characterized. Multiple X-ray crystal structures demonstrate the cis-folded pseudo-octahedral geometry forced by the rigidifying ethylene cross-bridge and show that two cis coordination cites are available for interaction with substrate and oxidant. The Cu complexes were used to determine kinetic stability under harsh acidic and high-temperature conditions, which revealed that the cyclam-based ligands provide superior stabilization with half-lives of many minutes or even hours in 5 M HCl at 50–90 °C. Cyclic voltammetry studies of the Fe and Mn complexes reveal reversible redox processes indicating stabilization of Fe2+/Fe3+ and Mn2+/Mn3+/Mn4+ oxidation states, indicating the likelihood of catalytic oxidation for these complexes. Finally, dye-bleaching experiments with methylene blue, methyl orange, and rhodamine B demonstrate efficient catalytic decolorization and allow selection of the most successful monomeric catalysts for copolymerization to produce future heterogeneous water purification materials.

Surgical management of head and neck squamous cell carcinoma (HNSCC) patients often requires resection of the deep cervical lymph nodes. Fluorescence guided surgery (FGS) is a growing area of oncologic surgery that has shown promise for this purpose, however, it is limited by the signal penetration through the neck. To address this, we sought to evaluate the efficacy of the anti-EGFR antibody [ In]panitumumab to detect metastatic lymph nodes both on preoperative imaging and intraoperatively. We hypothesized that the addition of a radiolabeled antibody would be safe and effective in detecting malignant tissue when given alone or together with the optical agent panitumumab-IRDye800CW (pan800). Seventeen patients were enrolled and received 5 mCi of [ In]panitumumab with nine patients (53%) receiving [ In]panitumumab and pan800. SPECT/CT scans were performed prior to surgical resection. Intraoperatively, patients underwent gamma tracing and the patients who received pan800 also underwent optical fluorescence imaging. Resected specimens were compared to final histopathology to determine the sensitivity and specificity of the two tracers. No adverse events related to the [ In]panitumumab were reported. SPECT/CT performed 3 days post-injection showed higher tumor-to-blood pool ratio compared to earlier scans (p = 0.04), and when compared to pathological assessment, could detect disease greater than 1 cm in diameter. Intraoperatively, resection of the primary tumor resulted in a significant drop in gamma counts (p < 0.001). detection of metastatic lymph nodes using the radiotracer was inconsistent and attributed to high background counts as patients who underwent surgery before 48 hours post-injection had significantly higher precordial counts than patients who underwent surgery after 48 hours, even when corrected for time, weight, and dose (p = 0.04). , metastatic lymph nodes had gamma counts almost twice that of benign (p < 0.0001). The separately dosed pan800 and [ In]panitumumab showed strong co-localization within metastatic lymph nodes (R = 0.87). Intravenous infusion of [ In]panitumumab in HNSCC patients is safe, whether administered alone or with pan800. Consistent with other studies, application of the radiotracer differentiated tumor containing tissue from benign. However, intraoperative use of the radiotracer to detect metastatic lymph nodes was limited by background signal at early timepoints and signal decay at later timepoints.

The clinical translation of molecularly targeted therapeutics and imaging agents represents a cornerstone of precision oncology, with the global theranostics market projected to exceed $25 billion by 2030. However, the development of theragnostic agents or diagnostic companions remains constrained by analytical bottlenecks in quality control, such as target-binding fraction, which are increasingly required by regulatory agencies as product release criteria during the translation process. Current methods, including enzyme-linked immunosorbent assay (ELISA), which require specialized resources or external CROs, or bead-based assays for radiolabeled compounds, which involve complex multi-step protocols; these limitations and others hamper their practical implementation in clinical manufacturing environments. Assay delays can postpone clinical trial initiation, increase development costs, and delay patient access to these agents. We have developed and validated a rapid, size-exclusion high-performance liquid chromatography (SE-HPLC) method for the determination of target-binding fractions of labeled biologics. The method separates the unbound biologic from the larger antigen-bound complex, allowing for rapid quantification. We validated the method using a panel of fluorescently labeled antibodies (panitumumab-IRDye800CW, nivolumab-IRDye800CW) and radiolabeled biologics ([18F]GEH200521, [18F]NOTA-ABY-030), assessing linearity, specificity, and concentration independence. The SE-HPLC method achieved excellent separation of bound and unbound species with a resolution (Rs) of 3.2. A strong linear relationship (R  = 0.999) was observed between the antigen-to-antibody ratio and the measured binding fraction. The method demonstrated high specificity, with no binding detected with non-target antigens. The total assay and analysis time was less than 35 min, a significant improvement over traditional methods. SE-HPLC provides a rapid, specific, and cost-effective alternative to traditional binding fraction assessment methods, reducing quality control timelines from weeks/hours to minutes. The method's compatibility with both fluorescent and radiolabeled biologics and integration with existing HPLC infrastructure represents a significant advancement in development workflows.

The clinical translation of molecularly targeted therapeutics and imaging agents represents a cornerstone of precision oncology, with the global theranostics market projected to exceed $25 billion by 2030. However, the development of theragnostic agents or diagnostic companions remains constrained by analytical bottlenecks in quality control, such as target-binding specificity, which are increasingly required by regulatory agencies as product release criteria during the translation process. Current methods, including enzyme-linked immunosorbent assay (ELISA), which require specialized resources or external CROs, or bead-based assays for radiolabeled compounds, which involve complex multi-step protocols; these limitations and others hamper their practical implementation in clinical manufacturing environments. Assay delays can postpone clinical trial initiation, increase development costs, and delay patient access to these agents. We have developed and validated a rapid, size-exclusion high-performance liquid chromatography (SE-HPLC) method for the determination of target-binding fractions of labeled biologics. The method separates the unbound biologic from the larger antigen-bound complex, allowing for rapid quantification. We validated the method using a panel of fluorescently labeled antibodies (panitumumab-IRDye800CW, nivolumab-IRDye800CW) and radiolabeled biologics ([18F]GEH200521, [18F]NOTA-ABY-030), assessing linearity, specificity, and concentration independence. The SE-HPLC method achieved excellent separation of bound and unbound species with a resolution (Rs) of 3.2. A strong linear relationship (R = 0.999) was observed between the antigen-to-antibody ratio and the measured binding fraction. The method demonstrated high specificity, with no binding detected with non-target antigens. The total assay and analysis time was less than 35 minutes, a significant improvement over traditional methods. SE-HPLC provides a rapid, specific, and cost-effective alternative to traditional binding fraction assessment methods, reducing quality control timelines from weeks/hours to minutes. The method's compatibility with both fluorescent and radiolabeled biologics and integration with existing HPLC infrastructure represents a significant advancement in development workflows.