High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery.

Dye design can influence the ability of fluorescently labeled imaging agents to generate tumor contrast and has become an area of significant interest in the field of fluorescence-guided surgery (FGS). Here, we show that the charge-balanced near-infrared fluorescent (NIRF) dye FNIR-Tag enhances the imaging properties of a fluorescently labeled somatostatin analogue. In vitro studies showed that the optimized fluorescent conjugate MMC(FNIR-Tag)-TOC bound primarily via somatostatin receptor subtype-2 (SSTR2), whereas its negatively charged counterpart with IRDye 800CW had higher off-target binding. NIRF imaging in cell line- and patient-derived xenograft models revealed markedly higher tumor contrast with MMC(FNIR-Tag)-TOC, which was attributed to increased tumor specificity. Ex vivo staining of surgical biospecimens from primary and metastatic tumors, as well as involved lymph nodes, demonstrated binding to human tumors. Finally, in an orthotopic tumor model, a simulated clinical workflow highlighted our unique ability to use standard preoperative nuclear imaging for selecting patients likely to benefit from SSTR2-targeted FGS. Our findings demonstrate the translational potential of MMC(FNIR-Tag)-TOC for intraoperative imaging and suggest broad utility for using FNIR-Tag in fluorescent probe development.

Sterility and Stability of Diluted Meloxicam in Compounded Multi-dose Vial after 365 Days.

Meloxicam is a common analgesic for rodents. Because meloxicam is only formulated commercially for companion animals, it requires dilution to achieve doses appropriate for small, laboratory species. Compounded multidose vial (cMDV) are often created to dilute and store a diluted drug. However, chronic cMDV use runs the risk of contamination and becoming a potential source of nosocomial infection. In this study, we created 15 cMDV by diluting meloxicam with sterile water (dilution, 1:10). cMDV were punctured once daily for 30 d. To determine the sterility of the diluted meloxicam, we assessed 8 cMDV for bacterial growth on days 0, 10, 20, 30, and 365 and tested them for endotoxin on days 0, 30, and 365. In addition, the stability of the remaining 7 cMDV was assessed on days 0, 10, 20, 30, and 365, by using liquid chromatography-diode assays. No bacterial growth or endotoxin was detected at any time point, and the drug concentrations remained stable over 365 d. Given the results this study, we believe that cMDV of diluted meloxicam can remain sterile and stable for 365 d.

Sterility and Stability of Diluted Carprofen in a Multidose Vial in the Laboratory Animal Setting.

Using compounded multidose vials (cMDV) is a common practice in the laboratory animal setting, where medications often are diluted to provide appropriate doses to rodents. However, bacterial contamination of MDV has been well established in both the human and veterinary medical literature. For this study, we created 14 cMDV by diluting carprofen into sterile water (dilution, 1:10) and stored 6 cMDV each at 5 and 24 °C. The stoppers of the cMDV were not cleaned with alcohol, and all were punctured twice daily for 28 d. The sterility of the diluted carprofen was evaluated by assessing bacterial growth on days 0, 7, 14, 21, and 28 and by testing for bacterial endotoxin on days 0 and 28. We used liquid chromatography-tandem mass spectrometry to assess the stability of 2 cMDV, with each cMDV being divided into the 2 storage-temperature subsets for days 0, 7, 14, 21, and 28. Neither bacterial contamination nor endotoxin was detected, and drug stability was stable over the 28 d. We suggest that with pragmatic techniques, such as secondary containment and consistent use of new needles, the contents of cMDV can remain sterile and stable for 28 d.