Tumor blood flow measured by PET dynamic imaging of first-pass 18F-FDG uptake: a comparison with 15O-labeled water-measured blood flow.

PET molecular imaging of 15O-labeled water is the gold standard for measuring blood flow in humans. However, this requires an on-site cyclotron to produce the short-lived 15O tracer, which is cost-prohibitive for most clinical PET centers. The purpose of this study was to determine if the early uptake of 18F-FDG could be used to measure regional blood flow in tumors in the absence of 15O-water. METHODS: PET scans were obtained in patients being evaluated for tumor perfusion and glucose metabolism in a phase I dose-escalating protocol for endostatin, a novel antiangiogenic agent. A 2-min perfusion scan was performed with a bolus injection of 2,220 MBq (60 mCi) of 15O-water, which was followed by a 370-MBq (10 mCi) dose of 18F-FDG. Four sequential scans of 18F-FDG uptake were acquired, consisting of an early 2-min uptake scan-or first-pass scan-and 3 sequential 15-min late 18F-FDG uptake scans. Regions of interest (ROIs) were drawn on 2 or more tumor sites and on back muscle, as a control ROI, for each patient. Arterial blood concentration was derived from the PET scans by drawing an ROI over a large artery in the field of view. Blood flow was computed with a simple 1-compartment blood flow model using the first 2 min of data after injection. RESULTS: Blood flow estimated from the early uptake of 18F-FDG was linearly correlated with 15O-measured blood flow, with an intercept of 0.01, a slope of 0.86, and an R2 regression coefficient of 0.74 (r = 0.86). The 18F-FDG tumor extraction fraction relative to 15O-water averaged 0.86. A preliminary case study of a patient with prostate cancer confirms the utility of the first-pass 18F-FDG blood flow analysis in tumor diagnosis. CONCLUSION: These results suggest that the first-pass uptake of 18F-FDG may provide an estimate of perfusion in a tumor within the limitations of incomplete extraction of 18F-FDG compared with 15O-water.     

Prevalence, challenges, and solutions for (18)F-FDG PET studies of obese patients: a technologist's perspective

Obesity has reached epidemic proportions in the United States; hence, it is frequently encountered in patients undergoing (18)F-FDG PET studies. The purpose of the current study was to present a technologist's perspective on the prevalence of obesity and the challenges and solutions in imaging obese patients in our PET facility. METHODS: From October 2002 to October 2003, whole-body (18)F-FDG PET was performed on 1,164 patients with a known or suspected malignancy. Images were acquired 45-60 min after (18)F-FDG injection (7.4 MBq [0.2 mCi]/kg, with a maximum of 925 MBq [25 mCi]) on a PET scanner using a 4-min emission and 3-min transmission time per bed position. A database was maintained of patient height and weight, and body mass index (BMI) was calculated. Patient obesity was classified as overweight (BMI > or = 25 kg/m(2)), obese (BMI > or = 30 kg/m(2)), or malignantly obese (BMI > or = 40 kg/m(2)). In addition, PET technologists recorded any problems and attempted solutions related to the patient weight. RESULTS: BMI calculations showed that 528 patients (45.4%) were overweight or obese (322 men and 206 women; mean age, 55 y). Of those, 201 (38%) were overweight, 270 (51%) were obese, and 57 (11%) were malignantly obese. Problems encountered in these patients included difficult intravenous access (15%), difficult patient positioning (10%), patient motion (7%), an incomplete study (emission only) (1%), and potentially higher radiation exposure to the technologist because of extra time spent near the patient. Attempted solutions included adjusting the schedule to allow more time per patient, adjusting the dose based on body weight, using varied positioning techniques, dividing the study to allow a respite between different image combinations, and dividing time spent with obese patients among the technologists involved. CONCLUSION: Excessive body weight and related problems have commonly been encountered in our PET facility. (18)F-FDG PET studies of obese patients represent an ongoing challenge, which requires patient-tailored solutions to avoid compromising image quality and risking higher radiation exposure to the technologists.     

Reproducibility of 18F-FDG microPET studies in mouse tumor xenografts.

(18)F-FDG has been used to image mouse xenograft models with small-animal PET for therapy response. However, the reproducibility of serial scans has not been determined. The purpose of this study was to determine the reproducibility of (18)F-FDG small-animal PET studies. METHODS: Mouse tumor xenografts were formed with B16F10 murine melanoma cells. A 7-min small-animal PET scan was performed 1 h after a 3.7- to 7.4-MBq (18)F-FDG injection via the tail vein. A second small-animal PET scan was performed 6 h later after reinjection of (18)F-FDG. Twenty-five sets of studies were performed. Mean injected dose per gram (%ID/g) values were calculated from tumor regions of interest. The coefficient of variation (COV) from studies performed on the same day was calculated to determine the reproducibility. Activity from the second scans performed after 6 h were adjusted by subtracting the estimated residual activity from the first (18)F-FDG injection. For 7 datasets, an additional scan immediately before the second injection was performed, and residual activity from this additional delayed scan was subtracted from the activity of the second injection. COVs of both subtraction methods were compared. Blood glucose values were measured at the time of injection and used to correct the %ID/g values. RESULTS: The COV for the mean %ID/g between (18)F-FDG small-animal PET scans performed on the same day 6 h apart was 15.4% +/- 12.6%. The delayed scan subtraction method did not produce any significant change in the COV. Blood glucose correction increased the COV. The injected dose, tumor size, and body weight did not appear to contribute to the variability of the scans. CONCLUSION: (18)F-FDG small-animal PET mouse xenograft studies were reproducible with moderately low variability. Therefore, serial small-animal PET studies may be performed with reasonable accuracy to measure tumor response to therapy.     

Comparison of lesion-to-cerebellum uptake ratios and standardized uptake values in the evaluation of lung nodules with 18F-FDG PET

OBJECTIVE: To evaluate the clinical performance of the lesion-to-cerebellum uptake ratio (LCR), a semiquantitative index for differentiating malignant from benign lung nodules with [F]fluorodeoxyglucose positron emission tomography (F-FDG PET). METHODS: Thirty-six patients (16 females, 20 males; median age, 73 years; range, 41-87 years) with 42 known or suspected malignant lung nodules underwent whole-body PET imaging after an intravenous injection of a mean dose of 543+/-69 MBq (14.7+/-1.9 mCi) of F-FDG. The standardized uptake value (SUV) and the LCR were calculated for each nodule and receiver operating characteristic (ROC) curves were analysed using the ROCKIT 0.9B software package. RESULTS: Surgical pathology and follow-up with serial computed tomography scans for at least 24 months revealed 18 malignant lung lesions and 24 benign lesions less than 3.0 cm in size. The mean LCR was 0.70+/-0.40 for malignant nodules and 0.23+/-0.12 for benign nodules (P<0.001, two-tailed test). The area under the estimated ROC curve was 0.8660 for SUV data and 0.9197 for LCR data (P=0.2408, two-tailed test). CONCLUSIONS: The LCR method appears to be a valuable semiquantitative index for the evaluation of malignancy in pulmonary nodules with F-FDG PET, which is simple to perform clinically and does not require accurate measurements of body weight or the residual activity in the syringe utilized for F-FDG injection.     

Is 18F-3'-fluoro-3'-deoxy-L-thymidine useful for the staging and restaging of non-small cell lung cancer?

The objective of this study was to compare 18F-3'-fluoro-3'-deoxy-L-thymidine (FLT) PET with clinical TNM staging, including that by 18F-FDG PET, in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC underwent whole-body 18F-FDG PET and whole-body 18F-FLT PET, using a median of 360 MBq of 18F-FDG (range, 160-500 MBq) and a median of 210 MBq of 18F-FLT (range, 130-420 MBq). 18F-FDG PET was performed 90 min after 18F-FDG injection, and 18F-FLT PET was performed 60 min after 18F-FLT injection. Two viewers independently categorized the localization and intensity of tracer uptake for all lesions. All 18F-FDG PET and 18F-FLT PET lesions were compared. Staging with 18F-FLT PET was compared with clinical TNM staging based on the findings of history, physical examination, bronchoscopy, CT, and 18F-FDG PET. From 8 patients, standardized uptake values (SUVs) were calculated. Maximal SUV and mean SUV were calculated. RESULTS: Sixteen patients with stage IB-IV NSCLC and 1 patient with strong suspicion of NSCLC were investigated. Sensitivity on a lesion-by-lesion basis was 80% for the 8 patients who received treatment before 18F-FLT PET and 27% for the 9 patients who did not receive pretreatment, using 18F-FDG PET as the reference standard. Compared with clinical TNM staging, staging by 18F-FLT PET was correct for 8 of 17 patients: 5 of 9 patients in the group with previous therapy and 3 of 8 patients in the group without previous therapy. The maximal SUV of 18F-FLT PET, at a median of 2.7 and range of 0.8-4.5, was significantly lower than that of 18F-FDG PET, which had a median of 8.0 and range of 3.7-18.8 (n = 8; P = 0.012). The mean SUV of 18F-FLT PET, at a median of 2.7 and range of 1.4-3.3, was significantly lower than that of 18F-FDG PET, which had a median of 6.2 and range of 2.8-13.9 (n = 6; P = 0.027). CONCLUSION: 18F-FLT PET is not useful for staging and restaging NSCLC.     

Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model.

Increased glucose metabolism of inflammatory tissues is the main source of false-positive (18)F-FDG PET findings in oncology. It has been suggested that radiolabeled nucleosides might be more tumor specific. METHODS: To test this hypothesis, we compared the biodistribution of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) and (18)F-FDG in Wistar rats that bore tumors (C6 rat glioma in the right shoulder) and also had sterile inflammation in the left calf muscle (induced by injection of 0.1 mL of turpentine). Twenty-four hours after turpentine injection, the rats received an intravenous bolus (30 MBq) of either (18)F-FLT (n = 5) or (18)F-FDG (n = 5). Pretreatment of the animals with thymidine phosphorylase (>1,000 U/kg, intravenously) before injection of (18)F-FLT proved to be necessary to reduce the serum levels of endogenous thymidine and achieve satisfactory tumor uptake of radioactivity. RESULTS: Tumor-to-muscle ratios of (18)F-FDG at 2 h after injection (13.2 +/- 3.0) were higher than those of (18)F-FLT (3.8 +/- 1.3). (18)F-FDG showed high physiologic uptake in brain and heart, whereas (18)F-FLT was avidly taken up by bone marrow. (18)F-FDG accumulated in the inflamed muscle, with 4.8 +/- 1.2 times higher uptake in the affected thigh than in the contralateral healthy thigh, in contrast to (18)F-FLT, for which this ratio was not significantly different from unity (1.3 +/- 0.4). CONCLUSION: In (18)F-FDG PET images, both tumor and inflammation were visible, but (18)F-FLT PET showed only the tumor. Thus, the hypothesis that (18)F-FLT has a higher tumor specificity was confirmed in our animal model.     

Dosimetry of the dopamine transporter radioligand 18F-FPCIT in human subjects.

This study was designed to evaluate the radiation dosimetry in human subjects for a new radiopharmaceutical, N-(3-(18)F-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane ((18)F-FPCIT). The goal was to determine a limiting dose consistent with accepted guidelines for use in clinical studies and to compare the radiation burden with other agents such as (123)I-FPCIT, (18)F-fluorodopa, and (18)F-FDG. METHODS: Dynamic PET scans of the urinary bladder were obtained in 6 subjects; 2 subjects had brain scans and 5 subjects had scans of the thorax or abdomen. Regions of interest were placed over composite images of each organ for which activity was visualized to generate time-activity curves. Doses were calculated from residence times using the MIRDOSE3 program. RESULTS: The critical organ for dosimetry is the urinary bladder wall with a dose of 0.0586 +/- 0.0164 mGy/MBq. The dose comes primarily (97.2%) from activity in the urinary bladder contents. The dose is lower than any of the other agents used commonly in PET to assess dopaminergic function. The effective dose equivalent (0.0120 mGy/MBq) is also lower than comparable compounds. CONCLUSION: (18)F-FPCIT has favorable dosimetry when compared with other agents used to study dopaminergic function. Doses as high as 853 MBq (23 mCi) may be given to adult patients and remain within accepted guidelines.     

Measurement of cerebral glucose metabolic rates in the anesthetized rat by dynamic scanning with 18F-FDG, the ATLAS small animal PET scanner, and arterial blood sampling.

Rodent models and genetically altered mice have recently become available to study many human diseases. A sensitive and accurate PET scanner for small animals would be useful to evaluate treatment of these diseases in rodent models. To examine the feasibility of performing quantitative PET studies, we performed dynamic scans with arterial blood sampling in anesthetized rats with the ATLAS (Advanced Technology Laboratory Animal Scanner) small animal PET scanner developed at the National Institutes of Health and (18)F-FDG and compared activities determined by PET scanning with those obtained by direct tissue sampling. METHODS: Dynamic PET scans after a bolus of approximately 48 MBq (1.3 mCi) (18)F-FDG were performed in rats anesthetized with isoflurane. Arterial blood sampling was performed throughout the scanning period. At 60 min the rat was killed, and the brain was rapidly removed and dissected into 5 structures (thalamus [TH], cortex [CX], brain stem [BS], cerebellum [CB], and half brain). Activity in the tissue samples was compared with the mean activity of the last 5 min of calibrated PET data. RESULTS: Plasma activity peaked at approximately 0.2 min and then cleared rapidly. Brain activity initially rose rapidly; the rate of increase then progressively slowed until activity was approximately constant between 30 and 60 min. Recovery coefficients (MBq/mL in PET images)/(MBq/mL in tissue samples) were 0.99 +/- 0.04, 0.90 +/- 0.19, 1.01 +/- 0.24, 0.84 +/- 0.05, and 1.01 +/- 0.17, respectively, in TH, CX, BS, CB, and half brain (mean +/- SD, n = 6-9). Cerebral glucose utilization determined by Patlak analyses of PET data measured 30-60 min after injection of (18)F-FDG was 31.7 +/- 5.2, 23.9 +/- 4.8, 29.9 +/- 5.0, 39.3 +/- 7.3, and 28.1 +/- 4.6 micro mol/100 g/min (mean +/- SD, n = 9) in TH, CX, BS, CB, and whole brain, respectively. These results are consistent with a previous (14)C-deoxyglucose study of the isoflurane-anesthetized rat. CONCLUSION: Expected values for glucose metabolic rates and recovery coefficients near unity suggest that quantitatively accurate dynamic (18)F-FDG brain imaging can be performed in the rat with arterial blood sampling and the ATLAS small animal PET scanner.     

Pretreatment evaluation of carcinomas of the hypopharynx and larynx with 18F-fluorodeoxyglucose, 123I-alpha-methyl-L-tyrosine and 99mTc-hexakis-2-methoxyisobutylisonitrile

While fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is helpful in the pretherapeutic evaluation of head and neck cancer, it is only available in selected centres. Therefore, single-photon emission tomography (SPET) tracers would be desirable if they were to demonstrate tumour uptake reliably. This multitracer study was performed to evaluate the pretherapeutic uptake of the SPET tracers iodine-123 alpha-methyl-L-tyrosine (IMT) and technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) in primary carcinomas of the hypopharynx and larynx and to compare the results with those of FDG PET. We examined 22 fasted patients (20 male, 2 female, mean age 60.5+/-10.2 years) with histologically confirmed carcinoma of the hypopharynx (n=9) or larynx (n=13), within 1 week before therapy. In 20 patients a cervical PET scan was acquired after intravenous injection of 232+/-43 MBq 18F-FDG. Data analysis was semiquantitative, being based on standardised uptake values (SUVs) obtained at 60-90 min after injection. After injection of 570+/-44 MBq 99mTc-MIBI, cervical SPET scans (high-resolution collimator, 64x64 matrix, 64 steps, 40 s each) were obtained in 19 patients, 15 and 60 min after tracer injection. Finally, 15 min after injection of 327+/-93 MBq 123I-IMT (medium-energy collimator, 64x64 matrix, 64 steps, 40 s each) SPET scans were acquired in 15 patients. All images were analysed visually and by calculating the tumour to nuchal muscle ratio. Eighteen of 20 (90%) carcinomas showed an increased glucose metabolism, with a mean SUV of 8.7 and a mean carcinoma to muscle ratio of 7.3. The IMT uptake was increased in 13 of 15 (87%) patients, who had a mean carcinoma to muscle ratio of 2.9. Only 13 of 19 (68%) carcinomas revealed pathological MIBI uptake, with a mean tumour to muscle ratio of 2.2 and no significant difference between early and late MIBI SPET images (P=0.23). In conclusion, in the diagnosis of primary carcinomas of the hypopharynx and larynx, IMT SPET achieved a detection rate comparable to that of FDG PET. IMT SPET was clearly superior to MIBI SPET in this population. A further evaluation of the specificity of IMT in a larger number of patients appears justified.     

Imaging gastric cancer with PET and the radiotracers 18F-FLT and 18F-FDG: a comparative analysis.

In this pilot study, we evaluated 3'-deoxy-3'-(18)F-fluorothymidine (FLT) PET for the detection of gastric cancer and compared the diagnostic accuracy with that of (18)F-FDG PET. METHODS: Forty-five patients (31 male and 14 female) with histologically proven locally advanced gastric cancer underwent attenuation-corrected whole-body (18)F-FLT PET and (18)F-FDG PET/CT (low-dose CT). (18)F-FLT emission images were acquired on a full-ring PET scanner 45 min after the injection of 270-340 MBq of (18)F-FLT. (18)F-FDG PET/CT was performed 60 min after the injection of 300-370 MBq of (18)F-FDG. Mean standardized uptake values for (18)F-FLT and (18)F-FDG were calculated using circular ROIs (diameter, 1.5 cm) in the primary tumor manifestation site, in a reference segment of the liver, and in the bone marrow and were compared on a lesion-by-lesion basis. RESULTS: According to the Lauren classification, 15 tumors (33%) were of the intestinal subtype and 30 (67%) of the nonintestinal subtype. (18)F-FLT PET images showed high contrast for the primary tumor and proliferating bone marrow. In all patients (45/45), focal (18)F-FLT uptake could be detected in the primary tumor. In contrast, 14 primary tumors were negative for (18)F-FDG uptake, with lesional (18)F-FDG uptake lower than or similar to background activity. The mean standardized uptake value for (18)F-FLT in malignant primaries was 6.0 +/- 2.5 (range, 2.4-12.7). In the subgroup of (18)F-FDG-positive patients, the mean value for (18)F-FDG was 8.4 +/- 4.1 (range, 3.8/19.0), versus 6.8 +/- 2.6 for (18)F-FLT (Wilcoxon test: P = 0.03). Comparison of mean (18)F-FLT and (18)F-FDG uptake in tumors with signet ring cells revealed no statistically significant difference between the tracers (6.2 +/- 2.1 for (18)F-FLT vs. 6.4 +/- 2.8 for (18)F-FDG; Wilcoxon test: P = 0.94). CONCLUSION: The results of this study indicate that imaging gastric cancer with the proliferation marker (18)F-FLT is feasible. (18)F-FLT PET was more sensitive than (18)F-FDG PET, especially in tumors frequently presenting without or with low (18)F-FDG uptake, and may improve early evaluation of response to neoadjuvant treatment.     

Uptake of cis-4-[18F]fluoro-L-proline in urologic tumors.

Tumor uptake of the amino acid cis-4-[18F]fluoro-L-proline (cis-FPro) was studied with PET in eight patients with urologic tumors. METHODS: Three patients had primary renal cell carcinomas (RCCs), one had a local recurrence of RCC, one had squamous RCC, one had an adrenal hemangioma, one had inguinal metastases of penile squamous carcinoma, and one had suspected metastatic disease from prostate cancer. PET scans of the trunk were acquired at 1 and 3-5 h after intravenous injection of 400 MBq cis-FPro and compared with 18F-FDG PET scans and CT. RESULTS: None of the tumors or metastases showed significant uptake of cis-FPro. FDG uptake was seen in one of the three primary RCCs, in the local recurrence of RCC, in the squamous RCC, and in the metastases of penile cancer. CONCLUSION: Cis-FPro appears not to be a promising PET tracer in oncology.     

Impact of patient weight and emission scan duration on PET/CT image quality and lesion detectability.

This study was performed to prospectively evaluate fast PET/CT imaging protocols using lutetium oxyorthosilicate (LSO) detector technology and 3-dimensional (3D) image-acquisition protocols. METHODS: Fifty-seven consecutive patients (30 male, 27 female; mean age, 58.6 +/- 15.7 y) were enrolled in the study. After intravenous injection of 7.77 MBq (0.21 mCi) of (18)F-FDG per kilogram, a standard whole-body CT study (80-110 s) and PET emission scan were acquired for 4 min/bed position in 49 patients and 3 min/bed position in 8 patients. One-minute-per-bed-position data were then extracted from the 3- or 4-min/bed position scans to reconstruct single-minute/bed position scans for each patient. Patients were subgrouped according to weight as follows: <59 kg (<130 lb; n = 15), 59-81 kg (130-179 lb; n = 33), and >or=82 kg (>or=180 lb; n = 9). Three experienced observers recorded numbers and locations of lesion by consensus and independently rated image quality as good, moderate, poor, or nondiagnostic. RESULTS: The observers analyzed 220 reconstructed whole-body PET images from 57 patients. They identified 114 lesions ranging in size from 0.7 to 7.0 cm on the 3- (n = 8) and 4-min/bed position images (n = 49). Of these, only 4 were missed on the 1-min/bed position scans, and all lesions were identified on the corresponding 2-min/bed position images. One- and 2-min/bed position image quality differed significantly from the 4-min/bed position image reference (P < 0.05). CONCLUSION: LSO PET detector technology permits fast 3D imaging protocols whereby weight-based emission scan durations ranging from 1 to 3 min/bed position provide similar lesion detectability when compared with 4-min/bed position images.     

Patterns of (18)F-FDG uptake in adipose tissue and muscle: a potential source of false-positives for PET.

The routine use of PET/CT fusion imaging in a large oncology practice has led to the realization that (18)F-FDG uptake into normal fat and muscle can be a common source of potentially misleading false-positive PET imaging in the neck, thorax, and abdomen. The goal of this study was to characterize this normal variant of (18)F-FDG uptake in terms of incidence and characteristic extent. METHODS: All body scans done on our PET/CT scanners in July and August 2002 were retrospectively reviewed. All cases in which increased (18)F-FDG uptake in the neck was not localized to lymph nodes or other obvious anatomic sites on the CT scans were included in this study. Sites of any unexplained (18)F-FDG uptake in the rest of the body were also recorded. RESULTS: A total of 863 PET scans (476 males, 387 females; age, 2-88 y; mean age, 57 y) were reviewed. The following distinctive patterns of nonpathologic (18)F-FDG activity were observed: (a) neck fat, 20 patients (2.3%); (b) paravertebral uptake, 12 patients (1.4%); (c) perinephric fat, 7 patients (0.8%); (d) mediastinal fat, 8 patients (0.9%); (e) normal musculature, 12 patients (1.4%). Patients showing paravertebral uptake, perinephric fat, and mediastinal fat were all associated with the neck fat pattern, singly or in combination. On the other hand, patients showing the normal musculature pattern did not show any of the other uptake. In this analysis, the incidence of (18)F-FDG uptake in sites other than the neck is restricted to the patient population with neck fat uptake and may be an underestimation of the true incidence. Neck fat is found predominantly in females, whereas normal musculature is usually seen in males (P < 0.01, Fisher exact test). Neck fat is also seen significantly more in the pediatric population (4/26 = 15%) than in the adult population (16/837 = 1.9%) (P < 0.01, Fisher exact test). CONCLUSION: Increased (18)F-FDG uptake is sometimes seen in individual muscles and in adipose tissue in the neck and shoulder region, axillae, mediastinum, and perinephric regions. There is also associated (18)F-FDG uptake in the intercostal spaces in the paravertebral regions. (18)F-FDG uptake in neck fat is more commonly seen in female patients and the pediatric population. The pattern of uptake as well as the age and sex distribution suggest that the (18)F-FDG in fat is in the brown adipose tissue. It is important to recognize this uptake pattern to avoid false interpretation of this benign normal variant as a malignant finding on (18)F-FDG PET scans.     

18F-FLT PET for visualization of laryngeal cancer: comparison with 18F-FDG PET.

The feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine PET (FLT PET) for detecting laryngeal cancer was investigated and compared with (18)F-FDG PET. METHODS: Eleven patients diagnosed with or strongly suspected of having recurrent laryngeal cancer and 10 patients with histologically proven primary laryngeal cancer underwent attenuation-corrected (18)F-FLT PET imaging 60 min after injection of a median of 213 MBq (range, 175-400 MBq) (18)F-FLT and attenuation-corrected (18)F-FDG PET imaging 90 min after injection of a median of 340 MBq (range, 165-650 MBq) (18)F-FDG. All patients were staged by endoscopy and CT according to the Union Internationale Contre la Cancer TNM staging system. All patients underwent biopsy of the laryngeal area after imaging. Lesions seen on (18)F-FDG PET and (18)F-FLT PET were compared with histopathologic results. Mean SUVs, maximum SUVs, and tumor-to-nontumor (TNT) ratios were calculated for (18)F-FLT and (18)F-FDG. Wilcoxon nonparametric testing was used for comparison of (18)F-FDG with (18)F-FLT uptake. The Spearman correlation coefficient was used to correlate mean SUVs, maximum SUVs, and TNT ratios of (18)F-FDG PET and (18)F-FLT PET. Two-tailed P values < 0.05 were considered significant. RESULTS: (18)F-FDG PET and (18)F-FLT PET detected laryngeal cancer correctly in 15 of 17 patients. One lesion judged as positive on (18)F-FDG PET turned out to be normal tissue. Of 2 lesions judged as positive on (18)F-FLT PET, 1 turned out to be inflammation and the other to be normal tissue. Maximum SUVs were 3.3 (range, 1.9-8.5) for (18)F-FDG and 1.6 (range, 1.0-5.7) for (18)F-FLT (P < 0.001). Mean SUVs were 2.7 (range, 1.5-6.5) for (18)F-FDG and 1.2 (range, 0.8-3.8) for (18)F-FLT (P < 0.001). TNT was 1.9 (range, 1.3-4.7) for (18)F-FDG and 1.5 (range, 1.1-3.5) for (18)F-FLT (P < 0.05). CONCLUSION: The numbers of laryngeal cancers detected with (18)F-FLT PET and (18)F-FDG PET were equal. In laryngeal cancer, the uptake of (18)F-FDG is higher than that of (18)F-FLT.     

Focal lung uptake of 18F-fluorodeoxyglucose (18F-FDG) without computed tomography findings

BACKGROUND: Integrated positron emission tomography/computed tomography (PET/CT) systems represent a major development allowing functional and anatomical information to be acquired in a single examination session and therefore providing a more accurate definition of suspected lesion characteristics. Together with the increasing number of clinical settings in which PET/CT scans have been advocated, however, pitfalls in image interpretation have been reported. METHODS: Four female subjects presenting a focal area of increased F-fluorodeoxyglucose (F-FDG) uptake with no evidence of a corresponding CT abnormality were included in the study. PET/CT scans were performed in all cases after the administration of 5.3 MBq . kg of F-FDG through a venous cannula. RESULTS: Focal high uptake of F-FDG was observed in lung lesions without anatomical counterparts on CT in four female cases. The only common feature to all was the paravenous injection of the radiotracer. CONCLUSION: The lesions detected by PET may be related to distal lung microembolism originating from the site of paravenous injection.     

Early prediction of response to chemotherapy in metastatic breast cancer using sequential 18F-FDG PET.

Chemotherapy is currently the treatment of choice for patients with high-risk metastatic breast cancer. Clinical response is determined after several cycles of chemotherapy by changes in tumor size as assessed by conventional imaging procedures including CT, MRI, plain film radiography, or ultrasound. The aim of this study was to evaluate the use of sequential 18F-FDG PET to predict response after the first and second cycles of standardized chemotherapy for metastatic breast cancer. METHODS: Eleven patients with 26 metastatic lesions underwent 31 (18)F-FDG PET examinations (240-400 MBq of 18F-FDG; 10-min 2-dimensional emission and transmission scans). Clinical response, as assessed by conventional imaging after completion of chemotherapy, served as the reference. 18F-FDG PET images after the first and second cycles of chemotherapy were analyzed semiquantitatively for each metastatic lesion using standardized uptake values (SUVs) normalized to patients' blood glucose levels. In addition, whole-body 18F-FDG PET images were viewed for overall changes in the 18F-FDG uptake pattern of metastatic lesions within individual patients and compared with conventional imaging results after the third and sixth cycles of chemotherapy. RESULTS: After completion of chemotherapy, 17 metastatic lesions responded, as assessed by conventional imaging procedures. In those lesions, SUV decreased to 72% +/- 21% after the first cycle and 54% +/- 16% after the second cycle, when compared with the baseline PET scan. In contrast, 18F-FDG uptake in lesions not responding to chemotherapy (n = 9) declined only to 94% +/- 19% after the first cycle and 79% +/- 9% after the second cycle. The differences between responding and nonresponding lesions were statistically significant after the first (P = 0.02) and second (P = 0.003) cycles. Visual analysis of 18F-FDG PET images correctly predicted the response in all patients as early as after the first cycle of chemotherapy. As assessed by 18F-FDG PET, the overall survival in nonresponders (n = 5) was 8.8 mo, compared with 19.2 mo in responders (n = 6). CONCLUSION: In patients with metastatic breast cancer, sequential 18F-FDG PET allowed prediction of response to treatment after the first cycle of chemotherapy. The use of 18F-FDG PET as a surrogate endpoint for monitoring therapy response offers improved patient care by individualizing treatment and avoiding ineffective chemotherapy.     

Improving evaluation of primary gastric malignancies by distending the stomach with milk immediately before 18F-FDG PET scanning

This study was designed to investigate the feasibility and effectiveness of a modified protocol for (18)F-FDG PET that was proposed to improve the identification of primary gastric malignancies. METHODS: In the modified protocol, patients were asked to drink 300-500 mL of cow milk to distend the stomach immediately before PET scans instead of fasting all along. For investigation of the influence of ingested milk on (18)F-FDG distributions, 43 nondiabetic patients without documented gastric diseases underwent both empty- and distended-stomach PET scans (79 and 72 scans, respectively) in their serial follow-up studies. For the evaluation of proven gastric malignancies, 24 patients who underwent distended-stomach PET scans were compared with 17 patients who underwent conventional empty-stomach examinations. RESULTS: Ingestion of milk nearly 1 h after (18)F-FDG injection had no significant influence on distributions to the heart (P = 0.16), mediastinum (P = 0.50), and liver (P = 0.49), whereas the percentages of intense and moderate uptake in the stomach changed from 38.0% and 59.5% to 0% and 11.1%, respectively. With the normal gastric wall distended, malignant lesions were observed with higher contrast and clearer outlines, and some of them were detected at a small size (1.2 cm) at an early stage and with mild uptake. CONCLUSION: Gastric distention with milk just before (18)F-FDG PET is a simple and effective method for improving the evaluation of primary gastric malignancies.     

The clinical impact of 18F-FDG gamma PET in patients with recurrent well differentiated thyroid carcinoma

The therapeutic approach to recurrent well-differentiated thyroid cancer is based on the detection of active disease. While a measured increase of thyroglobulin level in an ablated patient is highly suggestive of recurrence, localization of the tumour is necessary for adequate treatment planning. A whole body scan with 131I yields false negative results in the presence of non-iodophyllic foci of disease. Hypermetabolic foci of differentiated thyroid carcinoma can be detected by gamma PET with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG). This study retrospectively evaluated the therapeutic impact of the 18F-FDG scan in patients with suspected recurrent thyroid carcinoma in whom the iodine scan was negative. Twenty patients (five male, 15 female) aged 19-77 years, were suspected of having recurrent thyroid carcinoma due to elevated thyroglobulin levels and/or palpable neck findings. All whole body iodine scans obtained with diagnostic doses (74-148 MBq (2-4 mCi) of 131I), were reported normal, i.e., no iodophyllic foci were detected. Whole body gamma positron emission tomography (PET) imaging was performed in fasting patients following i.v. administration of 370 MBq (10 mCi) 18F-FDG, with a strict 1 h immobilization post-injection. Gamma PET results were validated either by anatomical imaging, repeat iodine scanning after administration of a therapeutic dose (at least 3,700 MBq (100 mCi) of 131I) or surgery. The impact of the FDG scan on patient management was evaluated by the referring physicians. Positive gamma PET results confirmed the presence of active disease in 14/15 patients. One false positive finding (fibrosis) and one false negative (carcinoid) were reported. Localization of hypermetabolic foci supported treatment decisions in 10 patients, and significantly altered therapeutic management in six others. Treatment was withheld in four patients with negative findings. The clinical impact of the scan in this patient group is similar to that reported in the literature and justifies its future implementation.     

Comparison of [18F]FDG-PET and L-3[123I]-iodo-alpha-methyl tyrosine (I-123 IMT)-SPECT in primary lung cancer

OBJECTIVE: The aim of this study was to evaluate L-3[123I]-iodo-alpha-methyl tyrosine (IMT)-SPECT and FDG-PET in pulmonary lesions suspected to be lung cancer. METHODS: Whole body PET (measured transmission corrected emission scans) was performed 45 minutes after i.v. injection of 222-370 MBq (6-10 mCi) 18F-FDG on a Siemens PET scanner (ECAT EXACT 47) including 5-6 bed positions. 123I-IMT-SPECT (chest) was performed after injection of 370 MBq (10 mCi) with a dual head camera (Picker Prism 2000) and commercially available reconstruction algorithms. Ten patients (6 male and 4 female) with suspected lung cancer were investigated. The results were compared to histological findings after surgery or bronchoscopic biopsies and CT. RESULTS: 123I-IMT-SPECT and FDG-PET were able to detect all 9 cases of lung cancer (1-8 cm in diameter). One case was true negative. Both imaging methods were true positive with respect to mediastinal lymph node metastases in one patient. The tumor/background ratio was higher with PET (8.20 vs. 2.84). CONCLUSION: Despite the limited number of patients it may be concluded that IMT-SPECT as well as FDG-PET are suited to correctly diagnose lung cancer. Nevertheless, FDG-PET, if available, seems to be better suited because of the higher tumor/background ratio and better resolution.     

The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are gaining the interest of researchers because of impressive metabolic response to the targeted molecular therapeutic drug imatinib mesylate. Initial reports suggest an impressive role for (18)F-FDG PET in follow-up of therapy for these tumors. However, the role of (18)F-FDG PET versus that of CT has not been established. Therefore, we compared the roles of (18)F-FDG PET and CT in staging and evaluation of early response to imatinib mesylate therapy in recurrent or metastatic GIST. METHODS: The study included 54 patients who underwent (18)F-FDG PET and CT scans within 3 wk before initiation of imatinib mesylate therapy. Forty-nine of these patients underwent repeat scans 2 mo after therapy. The numbers of sites or organs containing lesions on (18)F-FDG PET and CT scans were compared. Corresponding lesions on (18)F-FDG PET and CT scans or those confirmed to be malignant in appearance by other imaging modalities or on follow-up were considered true positives. Lesions seen on (18)F-FDG PET or CT scans but not seen or confirmed to be of benign appearance with other imaging modalities or on follow-up were considered false positives. Measurements of the maximum standard uptake value (SUV) on (18)F-FDG PET scans and tumor size on CT scans were used for quantitative evaluation of early tumor response to therapy. RESULTS: A total of 122 and 114 sites and/or organs were involved on pretherapy (18)F-FDG PET and CT scans, respectively. The sensitivity and positive predictive values (PPVs) for CT were 93% and 100%; whereas these values for (18)F-FDG PET were 86% and 98%. However, the differences between these values for CT and (18)F-FDG PET were not statistically significant (P = 0.27 for sensitivity and 0.25 for PPV). This suggests comparable performance of (18)F-FDG PET and CT in staging GISTs. Repeat scans at 2 mo after therapy showed agreement between (18)F-FDG PET and CT scans in 71.4% of patients (57.1% having a good response to therapy and 14.3% lacking a response). Discrepant results between (18)F-FDG PET and CT were recorded for 28.6% of the patients. (18)F-FDG PET predicted response to therapy earlier than did CT in 22.5% of patients during a longer follow-up interval (4-16 mo), whereas CT predicted lack of response to therapy earlier than (18)F-FDG PET in 4.1%. One patient did not undergo long-term follow-up. These findings suggest that (18)F-FDG PET is superior to CT in predicting early response to therapy in recurrent or metastatic GIST patients. CONCLUSION: The performances of (18)F-FDG PET and CT are comparable in staging GISTs before initiation of imatinib mesylate therapy. However, (18)F-FDG PET is superior to CT in predicting early response to therapy. Thus, (18)F-FDG PET is a better guide for imatinib mesylate therapy.