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Tryon Creek (35WA288) is an ancestral Nez Perce dwelling within Hells Canyon National Recreation Area in northeastern Oregon. The site consists of several household features located on an alluvial terrace west of the Snake River, dating between 1600-500 B.P. Here various flake attributes, abundance of heat-treatment, and raw material composition are compared across occupation levels. The spatial distribution of raw materials and heat-treatment across the site are quantitatively explored using measures of abundance and autocorrelation. The overall abundance of heat-treatment changes significantly through time, reflecting concomitant curation and lithic preparation. Clusters of heat-treated material, separated by raw material type and positioned away from fire-cracked rock (FCR), are also present through time, perhaps reflecting differences in activity zones. Overall, these methods provide a clearer picture of lithic preparation within the household and across time. [ABSTRACT FROM AUTHOR]

Clinical diagnosis of hepatocellular carcinoma (HCC) relies heavily on radiological imaging. However, information pertaining to liver cancer treatment such as the proliferation status is lacking. Imaging tumor proliferation can be valuable in patient management. This study investigated 18F-labeled clofarabine ([18F]CFA) targeting deoxycytidine kinase (dCK) for PET imaging of dCK-dependent proliferation in HCC. Since clinical PET scans showed a high liver background uptake of [18F]CFA, the aim of this study was to reduce this liver background uptake. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for imaging experiments. Several modifiers were tested and compared with the baseline PET scan: Forodesine, probenecid, and cold clofarabine, all applied before the hot [18F]CFA injection to evaluate the reduction in liver background uptake. Application of forodesine before hot [18F]CFA injection did not reduce the background uptake. Instead, it increased the background by 11.6–36.3%. Application of probenecid also increased the liver background uptake by 16.6–32.1%. Cold CFA application did reduce the liver background uptake of [18F]CFA, comparing to the baseline scan. Combining cold CFA with [18F]CFA for PET imaging of liver cancers is a promising strategy, worthy of further clinical evaluation. [ABSTRACT FROM AUTHOR]

Purpose: [11C]methionine ([11C]Met) was used for cancer imaging based on upregulated amino acid transport and protein synthesis in different tumor types. However, the short half-life of 11C decay limited further clinical development of [11C]Met. Synthetic amino acid analog anti-1-amino-3-[18F]fluoro-cyclobutyl-1-carboxylic acid ([18F]FCABC) was developed and FDA-approved for PET imaging of recurrent prostate cancer. This study investigated "repurposed" [18F]FACBC for PET imaging of primary liver cancer such as hepatocellular carcinoma (HCC) in comparison with [11C]Met. Methods: [11C]Met was synthesized in the lab, and [18F]FACBC was purchased from a commercial outlet. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for PET imaging. Bioinformatics analysis was performed for the expression of amino acid transporters responsible for radiotracer uptake and validated by PCR. Dynamic PET scans of [11C]Met and [18F]FACBC were acquired within 1 week. Standardized uptake value (SUV) was calculated for regions of interest (ROIs) defined over HCC and a liver background region. H&E staining and immunohistochemical (IHC) staining were performed with harvested tissues post-imaging. Results: Higher expression of ACST2 and LAT1 was found in HCC than in the surrounding liver tissues. PCR validated this differential expression. [11C]Met and [18F]FACBC displayed some differences in their uptake and retention in HCC. Both peaked in HCC with an SUV of 3.5 after 10 min post-injection. Met maintained a plateaued contrast uptake in HCC to that in the liver while [18F]FCABC declined in HCC and liver after peak uptake. The pathological assessment revealed the liver tumor as moderately differentiated similar to the human HCC and proliferative. Conclusion: Both [18F]FACBC and [11C]Met showed uptake in HCC through the use of a clinically relevant animal model of woodchuck HCC. The uptake and retention of [18F]FACBC and [11C]Met depend on their metabolism and also rely on the distribution of their principal amino acid transporters. [ABSTRACT FROM AUTHOR]

Clinical diagnosis of hepatocellular carcinoma (HCC) relies heavily on radiological imaging. However, information pertaining to liver cancer treatment such as the proliferation status is lacking. Imaging tumor proliferation can be valuable in patient management. This study investigated 18 F-labeled clofarabine ([ 18 F]CFA) targeting deoxycytidine kinase (dCK) for PET imaging of dCK-dependent proliferation in HCC. Since clinical PET scans showed a high liver background uptake of [ 18 F]CFA, the aim of this study was to reduce this liver background uptake. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for imaging experiments. Several modifiers were tested and compared with the baseline PET scan: Forodesine, probenecid, and cold clofarabine, all applied before the hot [ 18 F]CFA injection to evaluate the reduction in liver background uptake. Application of forodesine before hot [ 18 F]CFA injection did not reduce the background uptake. Instead, it increased the background by 11.6-36.3%. Application of probenecid also increased the liver background uptake by 16.6-32.1%. Cold CFA application did reduce the liver background uptake of [ 18 F]CFA, comparing to the baseline scan. Combining cold CFA with [ 18 F]CFA for PET imaging of liver cancers is a promising strategy, worthy of further clinical evaluation., Competing Interests: Y.S. holds patents and patent applications around decitabine, tetrahydrouridine, 5-azacytidine, and differentiation therapy agents to treat cancer with eligibility for royalties, ownership, board, and consultancy for EpiDestiny, none of which is a direct conflict of interest to the reported preclinical imaging study in this manuscript. All other authors declare that they have no competing interests.