Radiation dosimetry and biodistribution of the beta-amyloid plaque imaging tracer 11C-BTA-1 in humans.

AIM: [N-methyl-(11)C]2-(4'-(methylaminophenyl)-benzothiazole ((11)C-BTA-1) is a thioflavin-T derivative that has been one of the promising PET tracers for imaging of amyloid plaque distribution in the Alzheimer patients brain in vivo. The biodistribution and dosimetry of this tracer in humans is presented and compared to the results of a previous dosimetry and biodistribution study of another thioflavin-T derivative [N-methyl-(11)C]2-hydroxy-(4'-(methylaminophenyl)-benzothiazole ((11)C-OH-BTA-1) in baboons. METHODS: Five subjects underwent 2D dynamic PET imaging. Source organs were segmented using a semiautomatic algorithm based on clustering. Residence times for each source organ were determined by analytical integration of an exponential fit of the time activity curves. Finally organ doses were estimated using the software OLINDA/EXM. RESULTS: The administration of 286 +/- 93 MBq (11)C-BTA-1 was well tolerated by all subjects. Effective radiation dose was 4.3 microSv/MBq, range 3.6-5.0 microSv/MBq. In four of the five subjects the liver, in one of the subjects the gallbladder was the critical organ. CONCLUSION: The radiation burden of a single dose of 300 MBq (11)C-BTA-1 is within the accepted limits for research purpose. In contrast to the previous non-human primate study revealing the gallbladder as the critical organ for (11)C-6-OH-BTA-1, we found the liver as the critical organ in humans using (11)C-BTA-1. Possible explanations may be (1) a reduced bile concentration of (11)C-BTA-1 due to the absent OH-group or (2) a different hepatic metabolism of thioflavin derivatives in human and baboon.

Improved non-invasive T-Staging in non-small cell lung cancer by integrated 18F-FDG PET/CT.

AIM: In this prospective study, reliability of integrated (18)F-FDG PET/CT for staging of NSCLC was evaluated and compared to MDCT or PET alone. PATIENTS, METHODS: 240 patients (pts) with suspected NSCLC were examined using PET/CT. Of those patients 112 underwent surgery comprising 80 patients with NSCLC (T1 n = 26, T2 n = 37, T3 n = 11, T4 n = 6). Imaging modalities were evaluated independently. RESULTS: MDCT, PET and PET/CT diagnosed the correct T-stage in 40/80 pts (50%; CI: 0.39-0.61), 40/80 pts (50%; CI: 0.39-0.61) and 51/80 pts (64%; CI: 0.52-0.74), respectively, whereas equivocal T-stage was found in 15/80 pts (19%; CI: 0.11-0.19), 12/80 pts (15%; CI: 0.08-0.25) and 4/80 pts (5%; CI: 0.01-0.12), respectively. With PET/CT, T-stage was more frequently correct compared to MDCT (p = 0.003) or PET (p = 0.019). Pooling stages T1/T2, T-stage was correctly diagnosed with MDCT, PET and PET/CT in 54/80 pts (68%; CI: 0.56-0.78), 56/80 pts (70%; CI: 0.59-0.80) and 65/80 pts (81%; CI: 0.71-0.89). T3 stage was most difficult to diagnose. T3 tumors were correctly diagnosed with MDCT in 2/11 pts (18%; CI: 0.02-0.52) versus 0/11 pts (0%; CI: 0.00-0.28) with PET and 5/11 pts (45%; CI: 0.17-0.77) with PET/CT. In all imaging modalities, there were no equivocal findings for T4 tumors. Of these, MDCT found the correct tumor stage in 4/6 pts (67%; CI: 0.22-0.95), PET in 3/6 pts (50%; CI: 0.12-0.88) and PET/CT in 5/6 pts (83%; CI: 0.36-0.99). CONCLUSION: Integrated PET/CT was significantly more accurate for T-staging of NSCLC compared to MDCT or PET alone. The advantages of PET/CT are especially pronounced combining T1- and T2-stage as well as in advanced tumors.

Radiosynthesis and evaluation of [11C]BTA-1 and [11C]3'-Me-BTA-1 as potential radiotracers for in vivo imaging of beta-amyloid plaques.

AIM: To evaluate the in vitro and in vivo characteristics of [N-methyl-(11)C]2-(4'-(methylaminophenyl)-benzothiazole ([(11)C]BTA-1) as well as [N-methyl-(11)C]2-(3'-methyl-4'-(methylamino)phenyl)-benzothiazole ([(11)C]3'-Me-BTA-1) as diagnostic markers of amyloid-beta (Abeta) in Alzheimer's disease (AD). MATERIAL, METHODS: Brain uptake and clearance was determined in wild-type mice. Binding affinities (K(i)) of [(11)C]BTA-1 and [(11)C]3'-Me-BTA-1 for aggregated Abeta(1-40) fibrils were assessed. Autoradiography was performed on brain sections of AD patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in transgenic mice (Tg2576). Brain sections were analysed consecutively. Additionally, a [(11)C]BTA-1 PET study of an AD patient and a healthy control was performed. RESULTS: In mice brain uptake and clearance of [(11)C]BTA-1 is compatible with the half life of (11)C (2 min: 12.7 % ID/g; 30 min: 4.6% ID/g). In contrast clearance rate of [(11)C]3'-Me-BTA-1 is too slow (2 min 4% ID/g; 30 min 12% ID/g) to achieve sufficient clearance of free and non specifically bound radioactivity. K(i) of [(11)C]BTA-1 is 11 nmol/l and that of [(11)C]3'-Me-BTA-1 27 nmol/l. Both radioligands label Abeta selectively and specifically in AD patients and transgenic mice in vitro. The in vivo stained brain sections show a labelling of Abeta plaques. The AD patient has a higher prefrontal, parietal and striatal [(11)C]BTA-1 accumulation than the healthy control. Metabolite analysis revealed approximately 75% intact [(11)C]BTA-1 after 30min in plasma.[(11)C]BTA-1 is favourable for in vivo imaging of Abeta due to its rapid brain entry, sufficient clearance and good binding affinity for Abeta. CONCLUSION: The ability to label Abeta plaques in vivo in human subjects supports the suitability of [(11)C]BTA-1 as a plaque imaging agent.

Internal radionuclide therapy: software for treatment planning using tomographic data.

AIM: Accurate dosimetry must be performed for each patient before therapy with unsealed radionuclides. Recently, the software tool ULMDOS was developed to facilitate planar dosimetric calculations and to support traceability and documentation as a prerequisite for good clinical practice. Here, the extended version of ULMDOS for processing of tomographic data is presented. METHODS: ULMDOS is developed in IDL 6.1 (Interactive Data Language) under Windows XP/2000. Serial tomographic data can be loaded in an ECAT7 or DICOM format, and presented as maximum intensity projection. The definition of volumes of interest is supported by various tools (e.g., freehand, isocontour, polygon), region growing, and cluster analysis. Residence times are calculated from fits of the time activity data to exponential functions. RESULTS, DISCUSSION: Quantitative 3-dimensional data allow performing a more individualized dosimetry, as problems due to organ overlay, insufficient attenuation and scatter correction in the planar approach can be avoided. For traceability, documentation, retrospective examination and later processing all data can be saved in binary or ASCII format. Dosimetric calculations can be conducted within a single environment, thus it spares the time-consuming transfer of data between different software tools.

Dosimetry with (188)Re-labelled monoclonal anti-CD66 antibodies. A simplified approach based on a single measurement 3 h p.i.

AIM: For the therapeutic application of radiopharmaceuticals the activity is determined on an individual basis. Here we investigated the accuracy for a simplified assessment of the residence times for a (188)Re-labelled anti-CD66 monoclonal antibody. PATIENTS, METHODS: For 49 patients with high risk leukaemia (24 men, 25 women, age: 44 +/- 12 years) the residence times were determined for the injected (188)Re-labelled anti-CD66 antibodies (1.3 +/- 0.4 GBq, 5-7 GBq/mg protein, >95% (188)Re bound to the antibody) based on 5 measurements (1.5, 3, 20, 26, and 44 h p.i.) using planar conjugate view gamma camera images (complete method). In a simplified method the residence times were calculated based on a single measurement 3 h p.i. RESULTS: The residence times for kidneys, liver, red bone marrow, spleen and remainder of body for the complete method were 0.4 +/- 0.2 h, 1.9 +/- 0.8 h, 7.8 +/- 2.1 h, 0.6 +/- 0.3 h and 8.6 +/- 2.1 h, respectively. For all organs a linear correlation exists between the residence times of the complete method and the simplified method with the slopes (correlation coefficients R > 0.89) of 0.89, 0.99, 1.23, 1.13 and 1.09 for kidneys, liver, red bone marrow, spleen and remainder of body, respectively. CONCLUSION: The proposed approach allows reliable prediction of biokinetics of (188)Re-labelled anti-CD66 monoclonal antibody biodistribution with a single study. Efficient pretherapeutic estimation of organ absorbed dose may be possible, provided that a more stable anti-CD66 antibody preparation is available.

[PET and PET/CT in relapsing prostate carcinoma]. / PET und PET/CT in der Rezidivdiagnostik des Prostatakarzinoms.

Of patients with carcinoma of the prostate undergoing therapeutic regimes with curative intent, 15-23% will ultimately relapse and 16-35% will need some sort of salvage therapy within 5 years. Of relapsing patients, 50% will have local recurrence and 50% systemic disease with or without local recurrence. Therefore, localization of recurrent prostate cancer is critical for selecting a local or systemic therapeutic strategy. Modern fusion imaging with PET/CT and 11C/18F-choline or 11C-acetate has augmented the diagnostic imaging spectrum for assessment of relapsing prostate cancer. In 60-70% of patients with biochemical relapse, recurrent tumor can be detected and anatomically precisely localized. Detection sensitivity is probably negatively correlated with serum PSA concentration. Below a PSA level of 1 ng/ml, mean detection sensitivity is probably 50-66%. Fusion imaging with 11C-choline PET/CT and MRI possesses a high potential for early localization of recurrent prostate carcinoma.

[Advancement of PET and PET/CT in prostate carcinoma]. / Weiterentwicklung der PET und des PET/CT beim Prostatakarzinom.

Functional imaging of prostate carcinoma was examined with the metabolic substrates 2-(18)F-fluorodeoxyglucose, (11)C-methionine, (18)F-fluorodihydrotestosterone, (11)C-acetate and (11)C/(18)F-choline. Based on upregulated enzymes of phospholipid metabolism in prostate carcinoma, (11)C/(18)F-choline is preferentially incorporated into phosphatidylcholine of membrane lipids of prostate cancer cells. PET allows sensitive detection of the (11)C/(18)F-choline signal and PET/CT fusion imaging enables intraprostatic signal localisation. Most published studies report a high detection rate of prostate carcinoma with (11)C/(18)F-choline PET/CT. Differentiation of prostate carcinoma from benign hyperplasia and from focal chronic prostatitis may be difficult; acute prostatitis accumulates (11)C/(18)F-choline with an intensity comparable to prostate carcinoma.

In vivo evaluation of 5-[(18)F]fluoro-2'-deoxyuridine as tracer for positron emission tomography in a murine pancreatic cancer model.

We used a murine tumor progression model for the evaluation of potential proliferation markers using positron emission tomography (PET). 5-[(18)F]-2'-deoxyuridine ([(18)F]FdUrd) was synthesized with >98% radiochemical purity and investigated in a pancreatic cancer model, transforming growth factor alpha transgenic mice crossbred to p53 deficient mice. Thymidylate synthase was increased already in premalignant lesions, whereas thymidine kinase 1 mRNA levels were up-regulated 4-fold in the pancreatic cancer specimen of these mice. PET imaging was performed after injection of 1 MBq of [(18)F]FdUrd and 1 MBq of [(18)F]fluoro-deoxyglucose. Animals with pancreatic cancer displayed focal uptake of both tracers. The [(18)F]FdUrd uptake ratio closely correlated with the proliferation index as evaluated in morphometric and fluorescence-activated cell sorter analysis. These results indicate the potential of our tumor model for the evaluation of PET tracers and suggest [(18)F]FdUrd as a tracer for the assessment of proliferation in vivo.

Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography.

PURPOSE: Previous studies have shown that bone metastases are revealed by magnetic resonance imaging (MRI) or bone marrow scintigraphy several months before they are visible by conventional bone scintigraphy (BS). We present a new approach for detecting bone metastases in patients with breast cancer. We compared findings obtained with fluoride ion (F-18) and positron emission tomography (PET) with those obtained with conventional BS. PATIENTS AND METHODS: Thirty-four breast cancer patients were prospectively examined using F-18-PET and conventional BS. F-18-PET and BS were performed within 3 weeks of each other. Metastatic bone disease was previously known to be present in six patients and was suspected (bone pain or increasing levels of tumor markers, Ca(2+), alkaline phosphatase) in 28 patients. Both imaging modalities were compared by patient-by-patient analysis and lesion-by-lesion analysis, using a five-point scale for receiver operating characteristic (ROC) curve analysis. A panel of reference methods was used, including MRI (28 patients), planar x-ray (17 patients), and spiral computed tomography (four patients). RESULTS: With F-18-PET, 64 bone metastases were detected in 17 patients. Only 29 metastases were detected in 11 patients with BS. As a result of F-18-PET imaging, clinical management was changed in four patients (11.7%). For F-18-PET, the area under the ROC curve was 0.99 on a lesion basis (for BS, it was 0.74; P <.05) and 1.00 on a patient basis (for BS, it was 0.82; P <.05). CONCLUSION: F-18-PET demonstrates a very early bone reaction when small bone marrow metastases are present, allowing accurate detection of breast cancer bone metastases. This accurate detection has a significant effect on clinical management, compared with the effect on management brought about by detection with conventional BS.

Fluorine-18-FDG PET and technetium-99m antigranulocyte antibody scintigraphy in chronic osteomyelitis.

UNLABELLED: The aim of this study was to assess the usefulness of PET with 2-18F-fluoro-2-deoxy-D-glucose (FDG), as compared to immunoscintigraphy (IS) with 99mTc-labeled monoclonal antigranulocyte antibodies (AGAbs), in the detection of chronic osteomyelitis. METHODS: Fifty-one patients suspected of having chronic osteomyelitis in the peripheral (n = 36) or central (n = 15) skeleton were evaluated prospectively with static FDG PET imaging and combined 99mTc-AGAb/99mTc-methylene diphosphonate (MDP) bone scanning within 5 days. FDG PET and IS were evaluated in a blinded and independent manner by visual interpretation, which was graded on a five-point scale of two observers' confident diagnosis of osteomyelitis. Receiver operating characteristic (ROC) curve analysis was performed for both imaging modalities. The final diagnosis was established by means of bacteriologic culture of surgical specimens and histopathologic analysis (n = 31) or by biopsy and clinical follow-up over 2 yr (n = 20). RESULTS: Of 51 patients, 28 had osteomyelitis and 23 did not. According to the unanimous evaluation of both readers, FDG PET correctly identified 27 of the 28 positives and 22 of the 23 negatives (IS identified 15 of 28 positives and 17 of 23 negatives, respectively). The area under the ROC curve was 0.97/0.97 (reader 1/reader 2) for FDG PET and 0.87/0.90 for IS, with a high degree of interobserver concordance (K-values were 0.96 for FDG PET and 0.91 for IS). In the central skeleton, the ROC curve area was 0.98/1.00 for FDG PET and 0.71/0.77 for IS (p<0.05). On the basis of ROC analysis, the overall accuracies of FDG PET and IS in the detection of chronic osteomyelitis were 96%/96% and 82%/ 88%, respectively. With regard to the optimal threshold values, sensitivity and specificity were 100%/97% and 95%/95% with FDG PET, compared to 86%/92% and 77%/82% with IS, respectively. CONCLUSION: In the peripheral skeleton, both FDG PET and combined 99mTc-AGAb/99mTc-MDP scanning are appropriate imaging modalities to diagnose chronic osteomyelitis. FDG PET additionally allows reliable differentiation between osteomyelitis and infection of the surrounding soft tissue. In the central skeleton within active bone marrow, FDG PET is highly accurate and superior to AGAb imaging in the diagnosis of chronic osteomyelitis, which frequently presents as a nonspecific photopenic lesion at scintigraphy with labeled white blood cells.

FDG PET: elevated plasma glucose reduces both uptake and detection rate of pancreatic malignancies.

UNLABELLED: The aim of the study was to evaluate the effects of elevated plasma glucose levels on tumor detection. METHODS: One-hundred and seventy-one fasted patients (100 malignant pancreatic tumors, 46 chronic pancreatitis and 25 patients with other benign pancreatic lesions) were studied with 18F-fluorodeoxyglucose (FDG) PET before planned resective pancreatic surgery. Nineteen of 171 patients had elevated plasma glucose levels above 130 mg/dl, and 24 of 171 had diabetes mellitus. Standard uptake values (SUVs) with and without glucose correction, tumor-to-muscle ratios and tumor-to-liver ratios were measured of the pancreatic lesion respective of the area with the highest uptake within the pancreas. The original qualitative PET reports concerning the dignity of the pancreatic lesion were translated into a five-point malignancy scale. Tumor detection rates and SUVs were compared according to plasma glucose levels above and below 130 mg/dl, the presence of diabetes and by using receiver operating characteristic (ROC) analysis. RESULTS: The detection rates (and mean SUVs) for pancreatic malignancies were 86% and 42% (4.2 and 2.3) if fasted plasma glucose levels were below and above 130 mg/dl, respectively. The sensitivities (and mean SUVs of malignant tumors) were 83% and 69% (3.3 and 2.5) for patients without and with known diabetes. Areas under ROC curves were nearly equal for glucose corrected SUV and visual qualitative results (0.86 and 0.85), followed by uncorrected SUV (0.83), tumor-to-liver ratios (0.80) and tumor-to-muscle ratios (0.79). SUVs for chronic pancreatitis, muscle and liver had a tendency to increase with elevated plasma glucose levels. CONCLUSION: Negative PET results of patients with elevated plasma glucose should be interpreted with caution.

Overexpression of glucose transporter 1 and increased FDG uptake in pancreatic carcinoma.

UNLABELLED: Increased glycolysis is a characteristic metabolic feature of a malignant transformed phenotype. In cultured cells transformed by viruses or activated oncogenes, enhanced glycolytic metabolism is mediated by the overexpression of glucose transporter 1 (Glut-1) and key regulatory glycolytic enzymes. Whether increased glucose metabolism in solid human malignant tumors is related to the overexpression of key regulatory proteins of glucose metabolism is presently unknown. We thus studied the expression of Glut-1 and glucose uptake, assessed with 2-fluorodeoxyglucose (FDG) and PET in human pancreatic carcinoma (PC) and chronic mass-forming pancreatitis (MFP). METHODS: Glucose uptake was measured in the fasting state with FDG and PET in 12 patients with PC and 15 patients with MFP. The standardized uptake value (SUV) of FDG was determined as a global quantitative measure of tissue glucose utilization in cancer tissue or MFP. The expression of Glut-1 and Glut-4 was analyzed from operatively removed cancer or MFP tissue by Northern analysis or semiquantitative reverse transcriptase-polymerase chain reaction. The count ratio of Glut-1 to Glut-4 transcripts was used as an indicator of selective Glut-1 up-regulation. RESULTS: The SUVs of FDG in patients with cancer and MFP were 2.98 +/- 1.23 and 1.25 +/- 0.51 (p < 0.01), respectively. Northern analysis showed intense Glut-1 expression in four of five patients with cancer but not in any of the five patients with MFP that were tested. In PC, Glut-1 and Glut-4 transcripts were found in five of five and three of 10 patients, respectively, using reverse transcriptase-polymerase chain reaction, whereas in MFP, Glut-1 was detected in one of five and Glut-4 was detected in all five patients. The Glut-1-to-Glut-4 transcript ratios were 6.17 +/- 1.27 in patients with cancer and 0.42 +/- 0.12 in patients with MFP. The mean Glut-1 concentration in eight patients with cancer was 1.71 nmol of Glut-1 mRNA/microg of mRNA (range, 0.0446-9.43) and 0.15 (range, 0-1.55) (p < 0.05) in 13 patients with MFP. CONCLUSION: The concomitant enhancement of glucose utilization and selective overexpression of Glut-1 mRNA in pancreatic cancer but not in MFP suggested constitutive activation of Glut-1 gene or decreased degradation of Glut-1 mRNA in human pancreatic cancer. These findings may imply a potential for the early detection of pancreatic cancer with FDG and PET and identify new targets for anticancer therapy.

Radioimmunotherapy for the intensification of conditioning before stem cell transplantation: differences in dosimetry and biokinetics of 188Re- and 99mTc-labeled anti-NCA-95 MAbs.

UNLABELLED: A new concept is the intensification of preparative regimens for patients with advanced leukemia using monoclonal antibodies (MAbs) with an affinity for beta emitter-labeled bone marrow. 188Re is a high-energy beta emitter that has therapeutic promise. Our first aim was to clarify whether the therapeutic application of 188Re-MAb against nonspecific cross-reacting antigen 95 (NCA-95) can be predicted from biokinetic data derived from 99mTc-labeled NCA-95. Our second aim was to show that a radiation absorbed dose of > or =12 Gy in the bone marrow can be achieved using 188Re-MAb. METHODS: Dosimetric data were obtained for both radiotracers from multiple planar whole-body scans (double-head gamma camera), blood samples, and urine measurements from 12 patients with advanced leukemia. Radiation absorbed doses were calculated using MIRDOSE 3 software. RESULTS: Radiation absorbed doses to bone marrow, liver, spleen, lung, and kidney were 2.24, 0.50, 1.93, 0.05, and 0.90 mGy/MBq, respectively, using 99mTc-MAb and 1.45, 0.43, 1.32, 0.07, and 0.71 mGy/MBq, respectively, using 188Re-MAb. These differences were statistically significant for bone marrow, spleen, and kidney. The main differences were less accumulation of 188Re-MAb in bone marrow (31%+/-13% compared with 52%+/-13%) and faster elimination through urine (25%+/-3% compared with 15%+/-5% after 24 h). On the basis of these data, a mean marrow dose of 14+/-7 Gy was achieved in 12 patients suffering from leukemia after application of approximately 10+/-2 GBq 188Re-MAb. CONCLUSION: Myeloablative radiation absorbed doses can easily be achieved using 188Re-MAb. 99mTc- and 188Re-MAb showed similar whole-body distributions. However, direct prediction of radiation absorbed doses from the 99mTc-MAb, assuming identical biokinetic behavior, is not valid for the 188Re-MAb in a single patient. Therefore, individual dosimetry using 188Re-MAb is needed to calculate therapeutic activity.

Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET.

UNLABELLED: Radionuclide bone scanning (RNB) is considered to be the most practical screening technique for assessing the entire skeleton for skeletal metastases. However, RNB has been shown to be of lower sensitivity than MRI and CT in detecting osteolytic metastases. A prospective study was designed to evaluate the accuracy of planar RNB versus tomographic bone imaging with 18F-labeled NaF and PET (18F PET) in detecting osteolytic and osteoblastic metastases and its dependency on their anatomic localization. METHODS: Forty-four patients with known prostate, lung or thyroid carcinoma were examined with both planar RNB and 18F PET. A panel of reference methods including MRI of the spine, 1311 scintigraphy, conventional radiography and spiral CT was used as the gold standard. RNB and 18F PET were compared by a lesion-by-lesion analysis using a five-point score for receiver operating characteristic (ROC) curve analysis. RESULTS: 18F PET showed 96 metastases (67 of prostate carcinoma and 29 of lung or thyroid cancer), whereas RNB revealed 46 metastases (33 of prostate carcinoma and 13 of lung or thyroid cancer). All lesions found with RNB were also detected with 18F PET. Compared with 18F PET and the reference methods, RNB had a sensitivity of 82.8% in detecting malignant and benign osseous lesions in the skull, thorax and extremities and a sensitivity of 40% in the spine and pelvis. The area under the ROC curve was 0.99 for 18F PET and 0.64 for RNB. CONCLUSION: 18F PET is more sensitive than RNB in detecting osseous lesions. With RNB, sensitivity in detecting osseous metastases is highly dependent on anatomic localization of these lesions, whereas detection rates of osteoblastic and osteolytic metastases are similar. Higher detection rates and more accurate differentiation between benign and malignant lesions with 18F PET suggest the use of 18F PET when possible.

Prospective evaluation of the clinical value of planar bone scans, SPECT, and (18)F-labeled NaF PET in newly diagnosed lung cancer.

UNLABELLED: Previous studies have shown that vertebral bone metastases (BM) not seen on planar bone scintigraphy (BS) might be present on (18)F-fluoride PET scans or at MRI. Therefore, we evaluated the effect of SPECT or (18)F-labeled NaF PET ((18)F PET) imaging on the management of patients with newly diagnosed lung cancer. METHODS: Fifty-three patients with small cell lung cancer or locally advanced non-small cell lung cancer were prospectively examined with planar BS, SPECT of the vertebral column, and (18)F PET. MRI and all available imaging methods, as well as the clinical course, were used as reference methods. BS with and without SPECT and (18)F PET were compared using a 5-point scale for receiver operating characteristic (ROC) curve analysis. RESULTS: Twelve patients had BM. BS produced 6 false-negatives, SPECT produced 1 false-negative, and (18)F PET produced no false-negatives. The area under the ROC curve was 0.779 for BS, 0.944 for SPECT, and 0.993 for (18)F PET. The areas under the ROC curve of (18)F PET and BS complemented by SPECT were not significantly different, and both tomographic methods were significantly more accurate than planar BS. As a result of SPECT or (18)F PET imaging, clinical management was changed in 5 patients (9%) or 6 patients (11%), respectively. CONCLUSION: As indicated by the area under the ROC curve analysis, (18)F PET is the most accurate whole-body imaging modality for screening for BM. Routinely performed SPECT imaging is practicable, is cost-effective, and improves the accuracy of BS.

[18F] 3-deoxy-3'-fluorothymidine positron emission tomography: alternative or diagnostic adjunct to 2-[18f]-fluoro-2-deoxy-D-glucose positron emission tomography in the workup of suspicious central focal lesions?

BACKGROUND: 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography has been established as a standard diagnostic imaging method in the preoperative workup of suspicious pulmonary focal lesions, showing a sensitivity of more than 90% and a specificity of about 80%. Determination of malignant pulmonary lesions with FDG positron emission tomography depends on the assessment of glucose metabolism. However, false-positive findings can occur in inflammatory processes, such as sarcoidosis or pneumonia. The thymidine analogue 3-deoxy-3[(18)F]-fluorothymidine (FLT) is a new positron emission tomography tracer that more specifically targets proliferative activity of malignant lesions. The objective of this study was to determine whether FLT positron emission tomography, in comparison with FDG positron emission tomography, provides additional information in the preoperative workup of central pulmonary focal lesions. METHODS: In this prospective study FLT and FDG positron emission tomography examinations were performed as a part of the preoperative workup in 20 patients with histologically confirmed bronchial carcinoma, 7 patients with benign lesions, and 1 patient with an atypical carcinoid. Results were compared with final pathologic findings. RESULTS: For staging of the primary tumor, FLT positron emission tomography revealed a sensitivity of 86% and a specificity of 100% compared with a sensitivity of 95% and a specificity of 73% for FDG positron emission tomography. For N staging, the sensitivity of FLT positron emission tomography was 57% and the specificity was 100%, and for FDG positron emission tomography, the sensitivity was 86% and the specificity was 100%, respectively. CONCLUSIONS: Our preliminary findings indicate specific FLT uptake in malignant lesions. The number of false-positive findings in FDG positron emission tomography might be reduced with FLT positron emission tomography. Therefore positron emission tomography imaging with FLT represents a useful supplement to FDG in assessing the malignancy of central pulmonary focal lesions.

In vivo imaging of activated microglia using [11C]PK11195 and positron emission tomography in patients after ischemic stroke.

Neuroprotective strategies are currently being developed for stroke patients. Although the focus is on the development of early treatment the importance of late pathogenetic events is increasingly recognized. To investigate the microglial reaction in stroke we used a marker for activated microglia, [11C]PK11195, and PET in five patients with ischemic stroke 5-53 days after infarction. In one patient serial measurements were made. We demonstrated in each individual and at each point in time that a microglial reaction takes place in the area where T1 weighted MRI (magnetic resonance imaging) shows intensity changes. We consider this PET method as a promising tool to study the late pathogenetic consequences of cerebral infarction and to evaluate neuroprotective strategies with respect to the consequences of the microglial activation.

Values and limitations of 18F-fluorodeoxyglucose-positron-emission tomography with preoperative evaluation of patients with pancreatic masses.

The aim of this study was to determine the value and limitations of 18F-fluorodeoxyglucose (FDG)-position-emission tomography (PET) for differentiating benign and malignant pancreatic disease and for staging malignant disease. One hundred fifty-nine patients with 89 malignant and 70 benign pancreatic lesions all received PET, computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) before pancreatic surgery. The original reports were compared for all patients (group I; N = 159), for a subgroup that neither had fasting plasma glucose levels > or =130 mg/dL or known elevated levels of C-reactive protein ([CRP], group II; n = 123), and for the remaining patients (group III; n = 36). For group I, accuracy values (areas under receiver operating characteristic [ROC] curves) for differentiation of benign/malignant masses were 0.86 (PET), 0.93 (ERCP), 0.82 (CT), and 0.95 for ERCP + PET (N = 159). For group II, ROC areas increased to 0.92 (PET), 0.94 (p < 0.05; n = 123) (ERCP), 0.82 (CT), 0.97 (p < 0.05; n = 123) (ERCP + PET). The results for group III were 0.71 (PET), 0.81 (CT), and 0.93 (ERCP); (n = 36). With 54 patients of group II that either had contradictory or indeterminate/technically unsuccessful CT/ERCP, PET was correct in 43 patients (84%). Sensitivity/specificity for lymph node staging was 49%/63%, respectively. For patients with hepatic metastasis, PET was 70% sensitive and 95% specific, missing some metastasis that were <1 cm. PET detected peritoneal metastasis in 25% of patients, missing poorly localized microscopic spread. For selected patients who have indeterminate pancreatic masses but no hyperglycemia or serologic evidence of active inflammation, FDG-PET is an independent functional assay that significantly adds to the diagnostic accuracy of ERCP and CT in the differentiation of benign and malignant pancreatic disease. PET can reliably detect hepatic, peritoneal, and other distant metastases that are > or =1 cm.

Treatment of radioactive decay in pharmacokinetic modeling: influence on parameter estimation in cardiac 13N-PET.

Radioactive decay during measurement can be accounted for by either a decay correction of the measured data before modeling (DbM) or by direct implementation of decay into the pharmacokinetic model (DiM). The purpose of this study was to quantify the influence of the type of decay correction on the calculated parameters for the example of a three-compartment model used for the calculation of myocardial perfusion with 13N ammonia and positron emission tomography (PET). For a given input function [Ca(t)infinity t exp(-kt), k= 1.72/min] the tissue uptake for two parameter sets of K1, k2, k3, TBV were calculated for 20 frames (12 x 10 s, 4 x 30 s, 3 x 120 s, 1 x 300 s). These values were mathematically deteriorated by various noise levels according to Poisson statistics and fitted by a Levenberg-Marquardt algorithm. Estimated parameter means and coefficients of variation of the fitted parameters were calculated for the DbM and DiM case. The estimated parameter means for both decay correction methods were of comparable quality. The important measure for a single fit is the relative variability of the fitted parameters. This value is up to a factor 1.15 smaller for K1 obtained with DiM and a reasonable noise level of 10%. Therefore, decay correction should be taken into account during modeling to reduce the variability in the fitted parameters.

Simultaneous iterative reconstruction for emission and attenuation images in positron emission tomography.

The quality of the attenuation correction strongly influences the outcome of the reconstructed emission scan in positron emission tomography. Usually the attenuation correction factors are calculated from the transmission and blank scan and thereafter applied during the reconstruction on the emission data. However, this is not an optimal treatment of the available data, because the emission data themselves contain additional information about attenuation: The optimal treatment must use this information for the determination of the attenuation correction factors. Therefore, our purpose is to investigate a simultaneous emission and attenuation image reconstruction using a maximum likelihood estimator, which takes the attenuation information in the emission data into account. The total maximum likelihood function for emission and transmission is used to derive a one-dimensional Newton-like algorithm for the calculation of the emission and attenuation image. Log-likelihood convergence, mean differences, and the mean of squared differences for the emission image and the attenuation correction factors of a mathematical thorax phantom were determined and compared. As a result we obtain images improved with respect to log likelihood in all cases and with respect to our figures of merit in most cases. We conclude that the simultaneous reconstruction can improve the performance of image reconstruction.