Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging.

PURPOSE: The aim of this study is to compare glucose metabolism and hypoxia in four different tumor types using positron emission tomography (PET). (18)F-labeled fluorodeoxyglucose (FDG) evaluates energy metabolism, whereas the uptake of (18)F-labeled fluoromisonidazole (FMISO) is proportional to tissue hypoxia. Although acute hypoxia results in accelerated glycolysis, cellular metabolism is slowed in chronic hypoxia, prompting us to look for discordance between FMISO and FDG uptake. EXPERIMENTAL DESIGN: Forty-nine patients (26 with head and neck cancer, 11 with soft tissue sarcoma, 7 with breast cancer, and 5 with glioblastoma multiforme) who had both FMISO and FDG PET scans as part of research protocols through February 2003 were included in this study. The maximum standardized uptake value was used to depict FDG uptake, and hypoxic volume and maximum tissue:blood ratio were used to quantify hypoxia. Pixel-by-pixel correlation of radiotracer uptake was performed on coregistered images for each corresponding tumor plane. RESULTS: Hypoxia was detected in all four patient groups. The mean correlation coefficients between FMISO and FDG uptake were 0.62 for head and neck cancer, 0.47 for breast cancer, 0.38 for glioblastoma multiforme, and 0.32 for soft tissue sarcoma. The correlation between the overall tumor maximum standardized uptake value for FDG and hypoxic volume was small (Spearman r = 0.24), with highly significant differences among the different tumor types (P < 0.005). CONCLUSIONS: Hypoxia is a general factor affecting glucose metabolism; however, some hypoxic tumors can have modest glucose metabolism, whereas some highly metabolic tumors are not hypoxic, showing discordance in tracer uptake that can be tumor type specific.

Auramine orange stain with fluorescence microscopy is a rapid and sensitive technique for the detection of cervical lymphadenitis due to mycobacterial infection using fine needle aspiration cytology: a case series.

OBJECTIVE: We sought to evaluate the effectiveness of the auramine orange (AO) stain in diagnosing mycobacterial cervical adenitis (MCA) from fine needle aspiration (FNA) cytology. METHODS: A retrospective review of 19 patients evaluated at 2 urban hospitals from 2000 to 2003 for suspected MCA. FNA specimens were inoculated to culture media and had direct smears stained by the auramine acid fast method. RESULTS: Mycobacteria were identified in 16 (84.2%) of 19 AO-stained FNA specimens, with results available within 4 hours. Corresponding cultures were positive for mycobacteria in 12 specimens, 9 tuberculous and 3 nontuberculous, and grew Mycobacterium tuberculosis from the 3 AO-negative specimens. Three of the 4 patients with negative cultures had previously taken anti-mycobacterial medications. CONCLUSION: The AO stain with fluorescence microscopy is a sensitive and rapid method for detecting tuberculous and nontuberculous mycobacteria. It is a valuable tool for the otolaryngologists and pathologists in the diagnosis of MCA.

Radiation therapy does not impact local complication rates after free flap reconstruction for head and neck cancer.

OBJECTIVE: To determine whether external beam radiation therapy (XRT), administered either before or after surgery, increases the rate and/or severity of local postoperative complications in patients with head and neck cancer who undergo microvascular free flap reconstruction. DESIGN: Retrospective cohort study. SETTING: University of Washington Medical Center, Seattle, a tertiary care hospital. PATIENTS: A total of 100 consecutive patients underwent fibular free flap reconstruction of the mandible. The study cohort was divided according to radiation treatment status: (1) no XRT (28 patients), (2) preoperative XRT (37 patients), and (3) postoperative XRT (35 patients). The median follow-up after surgery was 11 months (range, 1-89 months). MAIN OUTCOME MEASURES: Rate and severity of local postoperative complications. RESULTS: Fifty-four patients (54%) had at least 1 postoperative complication. There were no differences among the 3 XRT subgroups in the overall proportion of patients with complications of any severity (15 [54%] of 28 patients in the no XRT group, 24 [65%] of 37 patients in the preoperative XRT group, and 16 [46%] of 35 patients in the postoperative XRT group; P = .26, chi(2) analysis). There were also no differences seen when mild and severe complication rates were specifically examined (P = .58 and P = .10, respectively). No case of complete flap loss was observed. We noted no significant correlations between the rate of postoperative complications and the following covariates: total radiation dose, size of radiation field, disease stage, exposure to chemotherapy, presence of serious medical comorbidities, patient age, or history of tobacco use. CONCLUSIONS: Our experience suggests that XRT can be safely administered before or after surgery to patients undergoing head and neck free flap reconstruction at an experienced surgical referral center. Postoperative complication rates were not significantly affected by administration, timing, dose, or extent of XRT.

Widefield optical imaging of changes in uptake of glucose and tissue extracellular pH in head and neck cancer.

The overall objective of this study was to develop an optical imaging approach to simultaneously measure altered cell metabolism and changes in tissue extracellular pH with the progression of cancer using clinically isolated biopsies. In this study, 19 pairs of clinically normal and abnormal biopsies were obtained from consenting patients with head and neck cancer at University of California, Davis Medical Center. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) and Alexa 647-pHLIP [pH (low) insertion peptide] was measured noninvasively by widefield imaging, and correlated with pathologic diagnosis. The results of widefield imaging of clinical biopsies demonstrated that 2-NBDG and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. The results also demonstrated the potential of this approach to detect subepithelial lesions. Topical application of the contrast agents generated a significant increase in fluorescence contrast (3- to 4-fold) in the cancer biopsies as compared with the normal biopsies, irrespective of the patient and location of the biopsy within a head and neck cavity. This unpaired comparison across all the patients with cancer in this study highlights the specificity of the imaging approach. Furthermore, the results of this study indicated that changes in intracellular glucose metabolism and cancer acidosis are initiated in the early stages of cancer, and these changes are correlated with the progression of the disease. In conclusion, this novel optical molecular imaging approach to measure multiple biomarkers in cancer has a significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.

High-resolution optical molecular imaging of changes in choline metabolism in oral neoplasia.

This study was aimed at developing an optical molecular imaging approach to measure differences in uptake and intracellular retention of choline in clinically isolated tissue biopsies from head and neck cancer patients. An optically detectable analogue of choline (propargyl choline) was synthesized and evaluated in 2D and 3D models and clinically isolated paired biopsies (n = 22 biopsies). Fluorescence contrast between clinically abnormal and normal tissues based on uptake and intracellular retention of propargyl choline was measured and correlated with pathologic diagnosis. Results in 2D and 3D models demonstrated a rapid uptake of propargyl choline in cancer cells, uniform permeation in tissue models, and specific detection of intracellular entrapped propargyl choline using the click chemistry reaction with an azide-modified Alexa 488 dye. Fluorescence imaging measurements following topical delivery of propargyl choline in clinically isolated biopsies showed that the mean fluorescence intensity (MFI) of neoplastic tissues was four-fold to five-fold higher than the MFI of clinically and pathologically normal samples. This difference in fluorescence contrast was measured on the basis of comparison of paired biopsy sets isolated from individual patients as well as comparison of clinically abnormal and normal biopsies independent of anatomic locations in the head and neck cavity and across diverse patients. In conclusion, a novel imaging approach based on monoalkyne-modified choline was developed and validated using cell and tissue models. Results in clinically isolated tissue biopsies demonstrate a significant fluorescent contrast between neoplastic and normal tissues and illustrate high specificity of the optical imaging approach.