(18)F-FET PET has a high sensitivity for the detection of high-grade brain tumors. Its specificity, however, is limited by passive tracer influx through a disrupted blood-brain barrier and (18)F-FET uptake in nonneoplastic brain lesions. Gliomas show specific tracer uptake in the absence of CE on MRI, which most likely reflects biologically active tumor.

68 Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N9,N99,N999-tetraacetic acid-D-Phe 1 -Tyr 3 -octreotide (DOTA-TOC) PET has proven its usefulness in the diagnosis of patients with neuroendocrine tumors. Radionuclide therapy ( 90 Y-DOTA-TOC or 177 Lu-DOTA-octreotate) is a choice of treatment that also requires an accurate diagnostic modality for early evaluation of treatment response. Our study compared 68 Ga-DOTA-TOC PET with CT or MRI using the Response Evaluation Criteria in Solid Tumors. Furthermore, standardized uptake values (SUVs) were calculated and compared with treatment outcome. Methods: Forty-six patients (29 men, 17 women; age range, 34-84 y) with advanced neuroendocrine tumors were investigated before and after 2-7 cycles of radionuclide therapy. Long-acting somatostatin analogs were not applied for at least 6 wk preceding the follow-up. Data were acquired with a dedicated PET scanner. Emission image sets were acquired at 90-100 min after injection. 68 Ga-DOTA-TOC PET images were visually interpreted by 2 experienced nuclear medicine physicians. For comparison, multislice helical CT scans and 1.5-T MRI scans were obtained. Attenuation-corrected PET images were used to determine SUVs. Repeated CT evaluation and other imaging modalities, for example, 18 F-FDG, were used as the reference standard. Results: According to the reference standard, 68 Ga-DOTA-TOC PET and CT showed a concordant result in 32 patients (70%). In the remaining 14 patients (30%), discrepancies were observed, with a final outcome of progressive disease in 9 patients and remission in 5 patients. 68 Ga-DOTA-TOC PET was correct in 10 patients (21.7%), including 5 patients with progressive disease. In these patients, metastatic spread was detected with the follow-up whole-body PET but was missed when concomitant CT was used. On the other hand, CT confirmed small pulmonary metastases not detected on 68 Ga-DOTA-TOC in 1 patient and progressive liver disease not detected on 68 Ga-DOTA-TOC in 3 patients. Quantitative SUV analysis of individual tumor lesions showed a large range of variability. Conclusion: 68 Ga-DOTA-TOC PET shows no advantage over conventional anatomic imaging for assessing response to therapy when all CT information obtained during follow-up is compared. Only the development of new metastases during therapy was detected earlier in some cases when whole-body PET was used. SUV analysis of individual lesions is of no additional value in predicting individual responses to therapy.

The objective of this study was to compare MRI response assessment with metabolic O-(2-18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET response evaluation during antiangiogenic treatment in patients with recurrent high-grade glioma (rHGG). Methods: Eleven patients with rHGG were treated biweekly with bevacizumab-irinotecan. MR images and 18 F-FET PET scans were obtained at baseline and at follow-up 8-12 wk after treatment onset. MRI treatment response was evaluated by T1/T2 volumetry according to response assessment in neurooncology (RANO) criteria. For 18 F-FET PET evaluation, an uptake reduction of more than 45% calculated with a standardized uptake value of more than 1.6 was defined as a metabolic response (receiver-operating-characteristic curve analysis). MRI and 18 F-FET PET volumetry results and response assessment were compared with each other and in relation to progression-free survival (PFS) and overall survival (OS). Results: At follow-up, MR images showed partial response in 7 of 11 patients (64%), stable disease in 2 of 11 patients (18%), and tumor progression in 2 of 11 patients (18%). In contrast, 18 F-FET PET revealed 5 of 11 metabolic responders (46%) and 6 of 11 nonresponders (54%). MRI and 18 F-FET PET showed that responders survived significantly longer than did nonresponders (10.24 vs. 4.1 mo, P 5 0.025, and 7.9 vs. 2.3 mo, P 5 0.015, respectively). In 4 patients (36.4%), diagnosis according to RANO criteria and 18 F-FET PET was discordant. In these cases, PET was able to detect tumor progression earlier than was MRI. Conclusion: In rHGG patients undergoing antiangiogenic treatment, 18 F-FET PET seems to be predictive for treatment failure in that it contributes important information to response assessment based solely on MRI and RANO criteria.

Somatostatin receptor scintigraphy is an accurate imaging modality for the diagnosis of neuroendocrine tumor. Because detection of distant metastases has a major impact on treatment, early diagnosis of metastatic spread is of great importance. So far, no standard procedure has become established for the early diagnosis of bone metastases from neuroendocrine tumor. We compared the diagnostic value of CT with that of the novel somatostatin analog 68 Ga-1,4,7,10-tetraazacyclododecane-N,N9,N$,N999-tetraacetic acid-D-Phe 1 -Tyr 3 -octreotide ( 68 Ga-DOTATOC) in the detection of such metastases. Methods: Fifty-one patients (22 women and 29 men; age range, 32-87 y) with histologically verified neuroendocrine tumor were included in this study. PET scans were fused with CT scans using a vacuum fixation device. 18 F-NaF or 99m Tc-dicarboxypropane diphosphonate bone scans or clinical follow-up served as the reference standard. Results: Twelve of the 51 patients had no evidence of bone metastases on any of the available imaging modalities, and 37 patients had 68 Ga-DOTATOC PET results true-positive for bone metastases. 68 Ga-DOTATOC PET results were true-negative for 12 patients, false-positive for one, and false-negative for another, resulting in a sensitivity of 97% and a specificity of 92%. 68 Ga-DOTATOC PET detected bone metastases at a significantly higher rate than did CT (P , 0.001). Furthermore, conventional bone scans confirmed the results of somatostatin receptor PET but did not reveal additional tumors in any patients. Conclusion: 68 Ga-DOTATOC PET is a reliable, novel method for the early detection of bone metastases in patients with neuroendocrine tumor. Our results show that CT and conventional bone scintigraphy are less accurate than 68 Ga-DOTATOC PET in the primary staging or restaging of neuroendocrine tumor.

Electrical high-frequency stimulation (HFS) of skin afferents elicits long-term potentiation (LTP)-like hyperalgesia in humans. Time courses were evaluated in the facilitating (homotopic) or facilitated (heterotopic) pathways to delineate the relative contributions of early or late LTP-like pain plasticity. HFS in healthy subjects (n=55) elicited highly significant pain increases to electrical stimuli via the conditioning electrode (to 145% of control, homotopic pain LTP) and to pinprick stimuli in adjacent skin (to 190% of control, secondary hyperalgesia). Individual time courses in subjects expressing a sufficient magnitude of hyperalgesia (>20% pain increase, n=28) revealed similar half-lives of homotopic pain LTP and secondary hyperalgesia of 6.9 h and 4.9 h (log(10) mean 0.839±0.395 and 0.687±0.306) and times to full recovery of 48 h and 24 h (log(10) mean 1.679±0.790 and 1.373±0.611). Time course and peak magnitudes were not correlated between (r=-0.19to+0.21, NS), nor within both readout (r=0.29 and 0.31, NS). In most subjects, time courses were consistent with early LTP1. Notably, in some subjects (10 of 28), estimated times to full recovery were much longer (>10 days), possibly indicating development of late LTP2-like pain plasticity. Dynamic mechanical allodynia (only present in 16 of 55 subjects) lasted for a shorter time than secondary hyperalgesia. Three different readouts of nociceptive central sensitization suggest that brief intense nociceptive input elicits early LTP1 of pain sensation (based on posttranslational modifications), but susceptible subjects may already develop longer-lasting late LTP2 (based on transcriptional modifications). These findings support the hypothesis that LTP may contribute to the development of persistent pain disorders.