The purpose of this study was to assess the prognostic value of early 18 F-FDG PET using standardized uptake value (SUV) compared with visual analysis in patients with diffuse large B-cell lymphoma (DLBCL). Methods: Ninety-two patients with newly diagnosed DLBCL underwent 18 F-FDG PET prospectively before and after 2 cycles of chemotherapy (at midtherapy). Maximum SUV (SUVmax) and mean SUV (SUVmean) normalized to body weight and body surface area, as well as tumor-to-normal ratios, were computed on the most intense uptake areas. The SUVs, tumor-to-normal ratios, and their changes over time were compared with visual analysis for predicting event-free survival (EFS) and overall survival, using receiver-operating-characteristic (ROC) analysis. Survival curves were estimated with KaplanMeier analysis and compared using the log-rank test. Results: With visual analysis, the accuracy of early PET to predict EFS was 65.2%. The 2-y estimate for EFS was 51% (95% confidence interval [CI], 34%-68%) in the PET-positive group compared with 79% (95% CI, 68%-90%) in the PET-negative group (P 5 0.009). An optimal cutoff value of 65.7% SUVmax reduction from baseline to midtherapy obtained from ROC analysis yielded an accuracy of 76.1% to predict EFS. The 2-y estimate for EFS was 21% (95% CI, 0%-42%) in patients with SUVmax reduction # 65.7% compared with 79% (95% CI, 69%-88%) in those with reduction . 65.7% (P , 0.0001). Fourteen patients considered as positive on visual analysis could have been reclassified as good responders. Conclusion: SUV-based assessment of therapeutic response during first-line chemotherapy improves the prognostic value of early 18 F-FDG PET compared with visual analysis in DLBCL.

We compared 18F-fluorocholine hybrid positron emission tomography/X-ray computed tomography (FCH-PET/CT) with ultrasonography (US) and scintigraphy in patients with hyperparathyroidism and discordant, or equivocal results of US and 123I/99mTc-sesta-methoxyisobutylisonitrile (sestaMIBI) dual-phase parathyroid scintigraphy. FCH-PET/CT was performed in 17 patients with primary (n = 11) lithium induced (n = 1) or secondary hyperparathyroidism (1 dialyzed, 4 renal-transplanted).The reference standard was based on results of surgical exploration and histopathological examination. The results of imaging modalities were evaluated, on site and by masked reading, on per-patient and per-lesion bases.In a first approach, equivocal images/foci were considered as negative. On a per-patient level, the sensitivity was for US 38%, for scintigraphy 69% by open and 94% by masked reading, and for FCH-PET/CT 88% by open and 94% by masked reading. On a per-lesion level, sensitivity was for US 42%, for scintigraphy 58% by open and 83% by masked reading, and for FCH-PET/CT 88% by open and 96% by masked reading. One ectopic adenoma was missed by the 3 imaging modalities. Considering equivocal images/foci as positive increased the accuracy of the open reading of scintigraphy or of FCH-PET/CT, but not of US. FCH-PET/CT was significantly superior to US in all approaches, whereas it was more sensitive than scintigraphy only for open reading considering equivocal images/foci as negative (P = 0.04). FCH uptake was more intense in adenomas than in hyperplastic parathyroid glands. Thyroid lesions were suspected in 9 patients. They may induce false-positive results as in one case of oncocytic thyroid adenoma, or false-negative results as in one case of intrathyroidal parathyroid adenoma. Thyroid cancer (4 cases) can be visualized with FCH as with 99mTc-sestaMIBI, but the intensity of uptake was moderate, similar to that of parathyroid hyperplasia.This pilot study confirmed that FCH-PET/CT is an adequate imaging tool in patients with primary or secondary hyperparathyroidism, since both adenomas and hyperplastic parathyroid glands can be detected. The sensitivity of FCH-PET/CT was better than that of US and was not inferior to that of dual-phase dual-isotope 123I/99mTc-scintigraphy. Further studies should evaluate whether FCH could replace 99mTc-sestaMIBI as the functional agent for parathyroid imaging, but US would still be useful to identify thyroid lesions.

Assessment of the response to treatment of metastases is crucial in daily oncological practice and clinical trials. For soft tissue metastases, this is done using computed tomography (CT), Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET) using validated response evaluation criteria. Bone metastases, which frequently represent the only site of metastases, are an exception in response assessment systems, because of the nature of the fixed bony defects, their complexity, which ranges from sclerotic to osteolytic and because of the lack of sensitivity, specificity and spatial resolution of the previously available bone imaging methods, mainly bone scintigraphy. Techniques such as MRI and PET are able to detect the early infiltration of the bone marrow by cancer, and to quantify this infiltration using morphologic images, quantitative parameters and functional approaches. This paper highlights the most recent developments of MRI and PET, showing how they enable early detection of bone lesions and monitoring of their response. It reviews current knowledge, puts the different techniques into perspective, in terms of indications, strengths, weaknesses and complementarity, and finally proposes recommendations for the choice of the most adequate imaging technique.

This prospective study aimed to compare the diagnostic performance of 18 F-fluorocholine and 18 F-FDG for detecting and staging hepatocellular carcinoma (HCC) in patients with chronic liver disease and suspected liver nodules. Methods: Whole-body PET/CT was performed in a random order at 10 min after injection of 4 MBq of 18 F-fluorocholine per kilogram and at 1 h after injection of 5 MBq of 18 F-FDG per kilogram. PET/CT results were read in a masked manner by 2 specialists, and diagnostic performance was assessed from the results of consensus masked reading. Those focal lesions appearing with increased or decreased activity, compared with background, on 18 F-fluorocholine PET/CT were considered positive for malignancy. The standard of truth was determined on a per-site basis using data from a histologic examination and a follow-up period of more than 6 mo; on a per-patient basis, the Barcelona criteria were also accepted as a proof of HCC in 5 patients. Results: Eighty-one patients were recruited; standard of truth was determined in 59 cases. HCC was diagnosed in 34 patients. Therefore, sensitivity was 88% for 18 F-fluorocholine and 68% for 18 F-FDG (P 5 0.07), and in 70 sites, sensitivity was 84% for 18 F-fluorocholine, significantly better than the 67% for 18 F-FDG (P 5 0.01). Of the 11 patients with well-differentiated HCC, 6 had a positive result with 18 F-fluorocholine alone, whereas 18 F-FDG was never positive alone; corresponding site-based sensitivity was 94% for 18 F-fluorocholine and 59% for 18 F-FDG (P 5 0.001). The detection rate of 18 sites corresponding to other malignancies was 78% for 18 F-fluorocholine and 89% for 18 F-FDG. In nonmalignant sites, 18 F-fluorocholine appeared less specific than 18 F-FDG (62% vs. 91% P , 0.01) because of uptake by focal nodular hyperplasia. Conclusion: 18 F-fluorocholine was significantly more sensitive than 18 F-FDG at detecting HCC, in particular in well-differentiated forms. In contrast, 18 F-FDG appeared somewhat more sensitive at detecting other malignancies and was negative in focal nodular hyperplasia. Thus 18 F-fluorocholine appears to be a useful PET/CT tracer for the detection and surveillance of HCC; however, performing PET/CT with both radiopharmaceuticals seems to be the best option.

As the main result of this pilot study, we show that in patients with hyperparathyroidism and with discordant or equivocal results on scintigraphy or on ultrasonography, adenomatous or hyperplastic parathyroid glands can be localized by FCH-PET/CT with good accuracy. Furthermore, FCH-PET/CT can solve discrepant results between preoperative ultrasonography and scintigraphy and has thus a potential as a functional imaging modality in the detection of abnormal parathyroid glands. Our preliminary results are encouraging and prompt us to further evaluate FCH-PET/CT as a functional imaging agent in patients with biochemical hyperparathyroidism.

Overexpression of the high affinity neurotensin receptor 1 (NTSR1), demonstrated in several human cancers, has been proposed as a new marker for human ductal pancreatic carcinoma and as an independent factor for poor prognosis for ductal breast cancer, head and neck squamous cell carcinoma, and non-small cell lung cancer. The aim of the present study was to develop new DOTA-neurotensin analogues for positron emission tomography (PET) imaging with (68)Ga and for targeted radiotherapy with (90)Y or (177)Lu. We synthesized a DOTA-neurotensin analogue series. Two of these peptides bear two sequence modifications for metabolic stability: DOTA-NT-20.3 shares the same peptide sequence as the previously described DTPA-NT-20.3. In the sequence of DOTA-NT-20.4, the Arg(8)-Arg(9) bond was N-methylated instead of the Pro(7)-Arg(8) bond in DOTA-NT-20.3. An additional sequence modification was introduced in DOTA-LB119 to increase stability. A spacer was added between DOTA and the peptide sequence to increase affinity. Binding to HT29 cells, which express NTSR1, in vivo stability, and biodistribution of the various analogues were compared, and the best candidate was used to image tumors of various sizes with the microPET in mice. (111)In-DOTA-NT-20.3, in spite of a relatively high uptake in kidneys, showed specific tumor uptake and elevated tumor to other organ uptake ratios. High contrast images were obtained at early time points after injection that allowed tumor detection at a time interval postinjection appropriate for imaging with the short-lived radionuclide (68)Ga. (111)In-DOTA-NT-20.4 displayed inferior binding to HT29 cells and reduced tumor uptake. (111)In-DOTA-LB119 displayed at early time points a significantly lower renal uptake but also a lower tumor uptake than (111)In-DOTA-NT-20.3, although binding to HT29 cells was similar. (68)Ga-DOTA-NT-20.3 displayed higher tumor uptake than (68)Ga-DOTA-LB119 and allowed the detection of very small tumors by PET. In conclusion, DOTA-NT-20.3 is a promising candidate for (68)Ga-PET imaging of neurotensin receptor-positive tumors. DOTA-NT-20.3 may also be considered for therapy, as the yttrium-labeled peptide has higher affinity than that of the indium-labeled one. A prerequisite for therapeutic application of this neurotensin analogue would be to lower kidney uptake, for example, by infusion of basic amino acids, gelofusin, or albumin fragments, to prevent nephrotoxicity, as with radiolabeled somatostatin analogues.

FCH provides a high detection rate for HCC, making it potentially useful in the initial evaluation of HCC or in the detection of recurrent disease. The favourable result of this proof-of-concept study opens the way to a phase III prospective study.

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