Preclinical assessment of hypoxic marker specificity and sensitivity.

PURPOSE: In the search for a sensitive, accurate, and noninvasive technique for quantifying human tumor hypoxia, our laboratory has synthesized several potential radiodiagnostic agents. The purpose of this study was to assess and compare the hypoxic marking properties of both radioiodinated and Tc-99m labeled markers in appropriate test systems which can predict for in vivo activity. MATERIALS AND METHODS: Preclinical assessment of hypoxic marker specificity and sensitivity employed three laboratory assays with tumor cells in vitro and in vivo. Radiolabeled marker uptake and/or binding to whole EMT-6 tumor cells under extremely hypoxic and aerobic conditions was measured and their ratio defined hypoxia-specific factor (HSF). Marker specificity to hypoxic tumor tissue was estimated from its selective avidity to two rodent tumors in vivo, whose radiobiologic hypoxic fractions (HF) had been measured. The ratios of % injected dose/gram (%ID/g) of marker at various times in EMT-6 tumor tissue relative to that in the blood and muscle of scid mice were used to quantify hypoxia-specific activity. This tumor in this host exhibited an average radiobiologic HF of approximately 35%. As well, nuclear medicine images were acquired from R3327-AT (HF approximately =15%) and R3327-H (no measurable HF) prostate carcinomas growing in rats to distinguish between marker avidity due to hypoxia versus perfusion. RESULTS: The HSF for FC-103 and other iodinated markers were higher (5-40) than those for FC-306 and other Tc-99m labeled markers. The latter did not show hypoxia-specific uptake into cells in vitro. Qualitative differences were observed in the biodistribution and clearance kinetics of the iodinated azomycin nucleosides relative to the technetium chelates. The largest tumor/blood (T/B) and tumor/muscle (T/M) ratios were observed for compounds of the azomycin nucleoside class in EMT-6 tumor-bearing scid mice. These markers also showed a 3-4 x higher uptake into R3327-AT tumors relative to the well-perfused R3327-H tumors. While both FC-306 and CERETEC rapidly distributed at unique concentrations to different tissues, their avidity to EMT-6 and R3327-AT tumors did not correlate with tumor HF. CONCLUSIONS: The halogenated azomycin nucleosides with the lowest lipid/water partition coefficient values were found to yield the optimal hypoxia-specific signal in these animal tumors. Our Tc-99m-labeled azomycin chelates showed little or no hypoxia-specific uptake and had in vivo biodistribution and clearance kinetics similar to those of CERETEC, a perfusion agent with no known hypoxic binding activity.

Imaging of childhood non-Hodgkin lymphoma: assessment by histologic subtype.

The types of childhood non-Hodgkin lymphoma (NHL) differ considerably from Hodgkin lymphoma and NHL seen in adults, both pathologically and clinically. Essential to understanding these differences is a knowledge of the three major histologic subtypes (undifferentiated, lymphoblastic, and large cell) that account for the vast majority of cases of pediatric NHL. Each of these subtypes has typical imaging and clinical features. The most common subtype, undifferentiated NHL, usually shows intraabdominal disease. Lymphoblastic tumors most frequently manifest as a mediastinal mass, perhaps with respiratory or circulatory compromise. Large cell tumors show heterogeneous clinical and imaging features but tend to spare the anterior mediastinum. Knowledge of the appropriate imaging modality to be used in evaluation of these tumors is also important. Computed tomography (CT) is the primary imaging modality for staging childhood NHL. Magnetic resonance imaging is best for examination of the central nervous system and bone involvement. Ultrasonography may be useful as a complementary study to abdominal CT; gallium scintigraphy also plays an adjunctive role to CT. Familiarity with typical and atypical patterns of tumoral behaviors and optimal imaging methods aid in the diagnosis and appropriate follow-up of these tumors.

Classification of community hospitals.

This articles describes the methodology, results, and potential applications of a study conducted by the authors to classify the nation's community hospitals. The classification system is offered as a preferable alternative to the system presently used by the Social Security Administration to implement Section 223 of the Social Security Amendments of 1972 (P.L. 92-603).