Conventional versus drug-eluting embolic transarterial chemoembolization with doxorubicin: comparative drug delivery, pharmacokinetics, and treatment response in a rabbit VX2 tumor model.

The purpose of this study was to compare intra-tumoral drug delivery, pharmacokinetics, and treatment response after doxorubicin (DOX) conventional (c-) versus drug-eluting embolic (DEE-) transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor model. Twenty-four rabbits with solitary liver tumors underwent c-TACE (n = 12) (1:2 water-in-oil emulsion, 0.6 mL volume, 2 mg DOX) or DEE-TACE (n = 12) (130,000 70-150 µm 2 mg DOX-loaded microspheres). Systemic, intra-tumoral, and liver DOX levels were measured using mass spectrometry up to 7-day post-procedure. Intra-tumoral DOX distribution was quantified using fluorescence imaging. Percent tumor necrosis was quantified by a pathologist blinded to treatment group. Lobar TACE was successfully performed in all cases. Peak concentration (CMAX, µg/mL) for plasma, tumor tissue, and liver were 0.666, 4.232, and 0.270 for c-TACE versus 0.103, 8.988, and 0.610 for DEE-TACE. Area under the concentration versus time curve (AUC, µg/mL ∗ min) for plasma, tumor tissue, and liver were 18.3, 27,078.8, and 1339.1 for c-TACE versus 16.4, 26,204.8, and 1969.6 for DEE-TACE. A single dose of intra-tumoral DOX maintained cytotoxic levels through 7-day post-procedure for both TACE varieties, with a half-life of 1.8 (c-TACE) and 0.8 (DEE-TACE) days. Tumor-to-normal liver DOX ratio was high (c-TACE, 20.2; DEE-TACE, 13.3). c-TACE achieved significantly higher DOX coverage of tumor vs. DEE-TACE (10.8% vs. 2.3%; P = 0.003). Percent tumor necrosis was similar (39% vs. 37%; P = 0.806). In conclusion, in a rabbit VX2 liver tumor model, both c-TACE and DEE-TACE achieved tumoricidal intra-tumoral DOX levels and high tumor-to-normal liver drug ratios, though c-TACE resulted in significantly greater tumor coverage.

PD-L1 Expression in Melanoma: A Quantitative Immunohistochemical Antibody Comparison.

Purpose: PD-L1 expression in the pretreatment tumor microenvironment enriches for response to anti-PD-1/PD-L1 therapies. The purpose of this study was to quantitatively compare the performance of five monoclonal anti-PD-L1 antibodies used in recent landmark publications.Experimental Design: PD-L1 IHC was performed on 34 formalin-fixed paraffin-embedded archival melanoma samples using the 5H1, SP142, 28-8, 22C3, and SP263 clones. The percentage of total cells (including melanocytes and immune cells) demonstrating cell surface PD-L1 staining, as well as intensity measurements/H-scores, were assessed for each melanoma specimen using a computer-assisted platform. Staining properties were compared between antibodies.Results: Strong correlations were observed between the percentage of PD-L1(+) cells across all clones studied (R2 = 0.81-0.96). When present, discordant results were attributable to geographic heterogeneity of the melanoma tissue section rather than differences in PD-L1 antibody staining characteristics. PD-L1 intensity/H-scores strongly correlated with percentage of PD-L1(+) cells (R2 > 0.78, all clones).Conclusions: The 5H1, SP142, 28-8, 22C3, and SP263 clones all demonstrated similar performance characteristics when used in a standardized IHC assay on melanoma specimens. Reported differences in PD-L1 IHC assays using these antibodies are thus most likely due to assay characteristics beyond the antibody itself. Our findings also argue against the inclusion of an intensity/H-score in chromogenic PD-L1 IHC assays. Clin Cancer Res; 23(16); 4938-44. ©2017 AACR.

High-definition Fourier Transform Infrared (FT-IR) spectroscopic imaging of human tissue sections towards improving pathology.

High-definition Fourier Transform Infrared (FT-IR) spectroscopic imaging is an emerging approach to obtain detailed images that have associated biochemical information. FT-IR imaging of tissue is based on the principle that different regions of the mid-infrared are absorbed by different chemical bonds (e.g., C=O, C-H, N-H) within cells or tissue that can then be related to the presence and composition of biomolecules (e.g., lipids, DNA, glycogen, protein, collagen). In an FT-IR image, every pixel within the image comprises an entire Infrared (IR) spectrum that can give information on the biochemical status of the cells that can then be exploited for cell-type or disease-type classification. In this paper, we show: how to obtain IR images from human tissues using an FT-IR system, how to modify existing instrumentation to allow for high-definition imaging capabilities, and how to visualize FT-IR images. We then present some applications of FT-IR for pathology using the liver and kidney as examples. FT-IR imaging holds exciting applications in providing a novel route to obtain biochemical information from cells and tissue in an entirely label-free non-perturbing route towards giving new insight into biomolecular changes as part of disease processes. Additionally, this biochemical information can potentially allow for objective and automated analysis of certain aspects of disease diagnosis.