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Intratumoral heterogeneity, which is manifested in almost all of the hallmarks of cancer, including the significantly altered metabolic profiles of cancer cells, represents a challenge to effective cancer therapy. High-throughput measurements of the metabolism of individual cancer cells would allow direct visualization and quantification of intratumoral metabolic heterogeneity, yet the throughputs of current measurement techniques are limited to about 120 cells per hour. Here, we show that single-cell photoacoustic microscopy can reach throughputs of approximately 12,000 cells per hour by trapping single cells with blood in an oxygen-diffusion-limited high-density microwell array and by using photoacoustic imaging to measure the haemoglobin oxygen change (that is, the oxygen consumption rate) in the microwells. We demonstrate the capability of this label-free technique by performing high-throughput single-cell oxygen-consumption-rate measurements of cultured cells and by imaging intratumoral metabolic heterogeneity in specimens from patients with breast cancer. High-throughput single-cell photoacoustic microscopy of oxygen consumption rates should enable the faster characterization of intratumoral metabolic heterogeneity.

This first study in humans was designed to evaluate the safety and dosimetry of a cellular proliferative marker, N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbenzamide (18F-ISO-1), and evaluate the feasibility of imaging tumor proliferation by PET in patients with newly diagnosed malignant neoplasms. Methods: Patients with biopsy-proven lymphoma, breast cancer, or head and neck cancer underwent 18F-ISO-1 PET. Tumor 18F-ISO-1 uptake was assessed semiquantitatively by maximum standardized uptake value, ratios of tumor to normal tissue and tumor to muscle, and relative distribution volume ratio. The PET results were correlated with tumor Ki-67 and mitotic index, from in vitro assays of the tumor tissue. The biodistribution of 18F-ISO-1 and human dosimetry were evaluated. Results: Thirty patients with primary breast cancer (n = 13), head and neck cancer (n = 10), and lymphoma (n = 7) were evaluated. In the entire group, tumor maximum standardized uptake value and tumor-to-muscle ratio correlated significantly with Ki-67 (τ = 0.27, P = 0.04, and τ = 0.38, P = 0.003, respectively), but no significant correlation was observed between Ki-67 and tumor–to–normal-tissue ratio (τ = 0.07, P = 0.56) or distribution volume ratio (τ = 0.26, P = 0.14). On the basis of whole-body PET data, the gallbladder is the dose-limiting organ, with an average radiation dose of 0.091 mGy/MBq. The whole-body and effective doses were 0.012 mGy/MBq and 0.016 mSv/MBq, respectively. No adverse effects of 18F-ISO-1 were encountered. Conclusion: The presence of a significant correlation between 18F-ISO-1 and Ki-67 makes this agent promising for evaluation of the proliferative status of solid tumors. The relatively small absorbed doses to normal organs allow for the safe administration of up to 550 MBq, which is sufficient for PET imaging in clinical trials.

The goal of the current study is to identify predictors responsible for mortality disparities between young (or =40 years) and older (40 years) women with breast cancer.From 1998 to 2006, 344 patientsor =40 years were treated for breast cancer. Cox regression models calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) to determine differences in breast cancer mortality in womenor =40 years versus40 years (n = 3,252), controlling for potential confounders in univariate tests.From 1998 to 2006, 3,596 patients were treated for breast cancer; 9.6% wereor =40 years and 90.4% were40 years. Young women were more likely to be African-American, with a family history of breast cancer, diagnosed at advanced stage, and treated by mastectomy (P0.05). Tumors in young women were more likely to be bilateral, T2/T3, grade III, ER/PR negative, and lymph-node positive (P0.01). Overall, young women (or =40 years) with breast cancer were more likely to die compared with older women (40 years) (aHR 1.52, CI 1.37-1.74).Young women (or =40 years) with breast cancer are diagnosed at a more advanced stage and have tumors with poor prognostic features. Young women (or =40 years) are 52% more likely to die from breast cancer compared to older women (40 years).

This study examined whether disparities in mammography use between women of differing socioeconomic status (SES; income and education) and varying access to medical care (healthcare insurance and routine medical check-up) remained over time despite overall increased breast cancer screening.Analysis of changes over time were made using data from the 1992, 1996, and 2000 Behavioral Risk Factor Surveillance System data from 53,846 women 50-69 years of age. Women who reported that they never had a mammogram were compared with those who ever had a mammogram. Multivariate logistic regression was used to determine whether and to what extent disparities between subgroups of women changed over time.The percentage of women 50-69 years of age who had never had a mammogram declined 65% from 22.1% in 1992 to 7.7% in 2000. Racial and ethnic differences in mammography prevalence disappeared over time. However, disparities among women of differing SES and among those with varying access to medical care remained based on multivariate analysis.Despite a substantial reduction in the proportion of women who had never had a mammogram among women 50-69 years of age from 1992 to 2000, disparities in use of mammography among the various population subgroups persisted.