Our objective was to determine whether early change in standardized uptake values (SUVs) of 3′deoxy-3′-18F-fluorothymidine (18F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC. Methods This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent 18F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%ΔSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of ΔSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed. Results Fifty-one of 90 recruited patients (median age, 54 y; stage IIA–IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Δ, 39%; 95% confidence interval, 31–46). There was a marginal difference in %ΔSUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for ΔSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50–0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). Conclusion 18F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy 18F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of 18F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test 18F-FLT PET in a more uniformly treated patient population.

A new, computerized segmentation technique, in which magnetic resonance (MR) imaging produces accurate volumetric measurements of brain and cerebrospinal fluid (CSF) without the limitations of computed tomography, was used in a retrospective analysis of digitized T2-weighted MR images of 16 healthy elderly control subjects and 16 patients with Alzheimer dementia. Ventricular and extraventricular CSF was quantified, and the effects of aging were studied; in both groups, the atrophy measurement was used to correct metabolic values obtained with positron emission tomography. Patients with Alzheimer dementia had higher total CSF; extraventricular, total ventricular, and third ventricular CSF volumes (49%, 37%, 99%, and 74%, respectively); and 7% lower brain volumes than the control group. The patients also showed a more marked decline in brain volumes and a greater increase in CSF volumes with advancing age than the control group. They had a 25.0% increase in corrected whole-brain metabolic rates; the control group had only a 15.8% increase. The use of this technique may provide a basis for further studies of aging and dementia, including regional volume analysis.

The concentrations of selected metabolites in the posterior temporoparietal cortex of 13 Alzheimer's diseased (AD) and four nondemented postmortem brains (of individuals between the ages of 63 and 95) were determined using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy. The estimates for glutamate and inositol for AD brains did not show any statistically significant difference (P > 0.05) from those for the nondemented brains. The putative neuronal marker N-acetyl aspartate (NAA), creatine, and GABA were decreased in AD brains compared with the nondemented brains. The estimates for creatine, glutamate, and GABA showed significant linear correlations with those of NAA. Creatine, glutamate, GABA, and NAA appeared to be negatively correlated with the neurofibrillary tangles. Our results support a neuronal loss in the posterior temporoparietal cortices of AD brains.

The concentrations of selected metabolites in the hippocampus and cerebellum of 13 Alzheimer's diseased (AD) and four nondemented postmortem brains were measured using high resolution 1H NMR spectroscopy. For both the hippocampal region and the cerebellum, the putative neuronal marker N-acetyl aspartate (NAA) was significantly lower in AD brains relative to the nondemented brains. For the hippocampal region, the NAA concentration correlated inversely with semiquantitative assessments of neuronal loss and neurofibrillary tangles. The gamma-aminobutyric acid levels in both hippocampus and cerebellum of an age- and a postmortem interval-matched subset of AD brains were lower than those of the controls. Because the cerebellum is generally thought to be unaffected by AD, the NAA decrease in the Alzheimer cerebellum may be due to lesions of either the Alzheimer or non-Alzheimer type in contralateral cerebrum.

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