Preferential labeling of glial and meningial brain tumors with [2-C-14]acetate

Acetate is preferentially transported into and metabolized by astrocytes, r ather than synaptosomes or neurons, and labeled acetate is used as a glial reporter molecule to assess glial metabolism and glial-neuronal interaction s. Because monocarboxylic acid transporter specificity might confer a pheno type to help localize, detect, and characterize brain tumors of glial origi n, use of [2-C-14]acetate and [C-14]deoxyglucose (a glucose analog metaboli zed by all brain cells) was compared in rat and human brain tumors. Methods : Cultured C6 glioma or U-373 glioblastoma/astrocytoma tumor cells were inj ected into the caudate nucleus of anesthetized CDF Fisher rats; 2-3 wk late r, an intravenous pulse of [2-C-14]acetate or [C-14]deoxyglucose was given, and timed blood samples were drawn during the 5- or 45-min experiment, res pectively. Local C-14 levels in the brain were assayed by quantitative auto radiography, and acetate uptake or glucose use was calculated. Uptake and m etabolism of the [C-14]acetate was also assayed in C6 glioma and human surg ical tumor samples in vitro. Results: [C-14]Acetate uptake into rat brain C 6 tumors was 9.9 +/-2.1 mL/100 g/min, compared with 3.9 +/-1.0 mL/100 g/min in contralateral tissue (n = 6; P<0.001), and was much higher than that in to other brain structures (e.g., 5:1 for white matter and 2:1 for cortical gray matter). Glucose use in C6 tumors was 111<plus/minus>34 mu mol/100 g/m in, versus 81 +/-5 mu mol/100 g/min in contralateral tissue (n = 6; P=0.08) ; no left-right differences in glucose use or acetate uptake were seen in o ther brain structures. The tumor-to-contralateral-tissue ratio for acetate (2.3 +/-0.3) exceeded that for deoxyglucose (1.4 +/-0.5) (P<0.05), indicati ng that acetate is a sensitive C6 glioma marker. [C-14]Acetate uptake also demarcated a few 3-wk-old C6 tumors that had unlabeled necrotic cores. U-37 3 tumors were smaller than C6 tumors in rat brain and were detected equally well with [C-14]acetate and [C-14]deoxyglucose. In vitro uptake of [C-14]a cetate into human glioblastoma or meningioma tumors was higher than uptake into pituitary adenoma. Rat C6 and human tumors with high uptake metabolize d acetate to acidic compounds and amino acids. Conclusion: Tumor imaging wi th radiolabeled acetate can help to localize and classify brain tumors. Tra nsporter and metabolic substrate specificity are traits that can be exploit ed further for in vivo imaging of brain glial tumors.