Metabolic imaging of ovarian tumors with carbon-11-methionine: a PET study.

UNLABELLED: This study examines the potential of 11C-methionine as a PET tracer in metabolic imaging of benign and malignant ovarian tumors. METHODS: Four patients with one or two benign ovarian tumors (endometriomas or cystadenomas), two patients with a tumor of borderline malignancy and seven patients with ovarian cancer were studied with 11C-methionine and PET before laparotomy. CT or MRI were performed as a reference. Tracer uptake was quantitated by calculating tracer standardized uptake values (SUVs) and the kinetic influx constants (Ki values). RESULTS: Benign or borderline malignant tumors did not accumulate 11C-methionine, whereas all carcinomas had significant uptake. The mean SUV of the primary carcinomas was 7.0 (s.d., 2.2) and the mean Ki was 0.14 min-1 (s.d., 0.1 min-1), but the distribution of tracer uptake was highly heterogenous in four of six tumors. CONCLUSION: Ovarian cancer can be imaged with 11C-methionine and PET. This method also may be of value in the differential diagnosis between benign and malignant ovarian neoplasms. Due to physiological accumulations and methodological limitations, the value of 11C-methionine PET in the staging of ovarian cancer appears to be limited.

Evaluation of response to radiotherapy in head and neck cancer by positron emission tomography and [11C]methionine.

PURPOSE: To evaluate the usefulness of positron emission tomography (PET) and L-[methyl-11C]methionine in assessing treatment response to radiotherapy in head and neck cancer. METHODS AND MATERIALS: Fifteen patients with head and neck cancer (13 with squamous cell carcinoma, 1 with adenocystic carcinoma, and 1 with paranasal plasmocytoma) underwent a PET study with [11C]-methionine both before and after preoperative radiotherapy to the total tumor dose of 61-73 Gy. Twelve primary and 12 metastatic tumor sites were within the field of view. Nineteen of the 24 tumor sites were surgically explored after radiotherapy, and the tumor standardized uptake values (SUVs) of [11C]methionine were compared with histological findings. RESULTS: All 24 malignant lesions were detectable in the pretreatment study. In all but one case, the tumor SUV decreased after radiotherapy. The median SUV of the tumor site was smaller (1.9, range, 1.3-3.1, n = 7) in cases with histologically verified complete response than in cases with persistent cancer (median 4.1, range, 2.8-7.6, n = 12, p = 0.0008). A complete histological response was verified in none of the 9 cases with a postirradiation SUV larger than the median (3.1), whereas 7 of the 10 cases with a SUV of 3.1 or smaller had complete response (p = 0.003). The preirradiation uptake of [11C]methionine in tumors did not have significant association with histological response (p = 0.45). The PET findings correlated well with follow-up data in five cases with unoperated tumor sites. The [11C]methionine uptake of the submandibular salivary glands decreased after radiotherapy (p = 0.04). CONCLUSION: PET with [11C]methionine as a tracer may be useful in assessing response to radiotherapy in head and neck cancer. High uptake of [11C]methionine in the postirradiation scan suggests the presence of persistent disease.

Imaging of head and neck tumors with positron emission tomography and [11C]methionine.

PURPOSE: To evaluate the value of positron emission tomography and [11C]methionine in imaging of malignant tumors of the head and neck region. METHODS AND MATERIALS: Forty-seven tumors of the head and neck were investigated with 11C-labeled methionine and positron emission tomography before treatment. Because of the resolution limits of the positron emission tomography scanner, all tumors selected for the study were larger than 1 cm in diameter. RESULTS: Forty-two (91%) of the 46 malignant tumors were clearly visible in the positron emission tomography image (squamous cell carcinoma, n = 26; lymphoma, n = 9; adenocystic carcinoma, n = 2; lymphoepithelioma, n = 1; adenocarcinoma, n = 1; transitional cell carcinoma, n = 1; esthesioneuroblastoma, n = 1; plasmocytoma, n = 1), while three (7%) squamous cell carcinomas were visible, but less easy to detect due to physiological accumulation of the tracer in the area under observation. Only one (2%) squamous cell carcinoma could not be delineated from the positron emission tomography image, and there was no uptake of [11C]methionine in a benign pleomorphic adenoma. No correlation was found between the uptake of [11C]methionine and the histological grade in the subset of squamous cell carcinoma (n = 30). High physiological uptake of [11C]methionine was observed in the salivary glands and the bone marrow. CONCLUSIONS: Malignant head and neck tumors can be effectively imaged with positron emission tomography using [11C]methionine as the tracer.

Imaging of uterine carcinoma by carbon-11-methionine and PET.

UNLABELLED: L-[methyl-11C]methionine ([11C]methionine) is probably one of the most useful positron-emitting tracers for metabolic imaging of human cancer. In this study, we investigated whether human uterine cancer can be imaged with [11C]methionine and PET. METHODS: Fourteen patients with primary uterine malignancy participated in the study. Eight patients had endometrial carcinoma and six had cervical carcinoma. The normal endometrium was analyzed in four additional patients with no uterine malignancy and in one patient with cervical cancer. Tracer uptake was quantitated by calculating both the standardized uptake values (SUVs) and the kinetic influx constants (Ki values) for the tracer. RESULTS: All patients with either cervical or endometrial carcinoma had increased uptake of [11C]methionine in the PET image. The mean SUV of the carcinomas was 8.4 (n = 13; s.d., 1.5) and the mean Ki was 0.15 min-1 (n = 12; s.d., 0.08 min-1), whereas the mean SUV of the normal endometrium was only 4.6 (n = 5; s.d., 0.8). Histologically poorly (Grade III) or moderately (Grade II) differentiated endometrial carcinomas accumulated more [11C]methionine than the well-differentiated (Grade I) ones (p = 0.04 for the SUVs, and p = 0.05 for the Ki values). There were also variable physiological accumulations of [11C]methionine in the pelvis. CONCLUSIONS: Uterine carcinoma accumulated [11C]methionine more than the normal endometrium. However, the physiological accumulations of [11C]methionine in the pelvis may confuse the interpreter of the PET image; thus, morphological imaging also needs to be performed as a reference to localize the tumor accurately. We conclude that human uterine carcinoma can be effectively imaged with [11C]methionine and PET.

Positron emission tomography in oncology.

The particular advantages of positron emission tomography (PET) technique are that it has higher sensitivity, higher resolution, and a higher quality of image than that found in conventional nuclear medicine. The possibility of quantification and the wide range of useful tracers have raised expectations of this new method. To date, most of the human PET cancer studies have been performed with [18F]fluorodeoxyglucose (FDG) or [11C]methionine. These are good imaging agents for tumours. However, more specific radiopharmaceuticals are required if other features of tumour metabolism are to be observed. [11C]Thymidine may prove to be a good tracer for quantitative measurements of tumour proliferation and [18F]misonidazole has been suggested for imaging of hypoxia.

Head and neck cancer: effect of food ingestion on uptake of C-11 methionine.

PURPOSE: To determine the influence of a standardized meal on tumor uptake measured with positron emission tomography (PET) and L-(methyl-carbon-11) methionine. MATERIALS AND METHODS: Five patients with untreated squamous cell cancer of the head and neck underwent PET, first in a fasting state and then 6-7 days later after ingesting a liquid meal. RESULTS: All tumors were seen on PET scans, and image quality remained good after food ingestion. The standardized uptake values of the tumors were 3.7-11.4 in the fasting state but decreased after the meal (range, 3.3-10.0; P < .04). No substantial change was measured in tumor C-11 methionine influx constants (Ki values). CONCLUSION: Although cancer imaging with PET and C-11 methionine can be performed even in the patient has not fasted, a standardized meal may decrease tumor C-11 methionine uptake.

Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine in head and neck cancer.

The positron emission tomography (PET) tracer 2-18F-fluoro-2-deoxy-D-glucose (FDG) is the most widely used tracer in oncology. PET tracer. Another radiotracer, L-methyl-11C-Methionine (11C-methionine), also has been used successfully for PET imaging of brain and lung tumors, non-Hodgkin's lymphoma, breast cancer and head and neck cancer. This study compared FDG and 11C-methionine as tumor-detecting agents in head and neck cancer. Prior to cancer therapy, fourteen patients underwent a PET study with FDG and one with 11C-methionine. Nineteen of 21 malignant lesions that could be evaluated were visible with both tracers. Tracer uptake was measured as standardized uptake values (SUV) and Ki values according to Patlak et al. The mean SUV in FDG studies was 7.7 +/- 4.2 and in 11C-methionine studies 7.7 +/- 2.5, whereas the Ki values in 11C-methionine studies (mean, 0.128 +/- 0.068 min-1) were always higher than in FDG studies (mean, 0.036 +/- 0.023 min-1). A good correlation was found between the SUVs (r = 0.79, p < 0.0001) and the Ki values (r = 0.82, p < 0.001) between the two tracers. Both FDG and 11C-methionine are effective in PET imaging of head and neck cancer, and the uptake rates of the tracers seem to be closely related.

Carbon-11-methionine and PET in evaluation of treatment response of breast cancer.

Uptake of L-methyl-11C-methionine (11C-methionine) in breast cancer metastases was studied with positron emission tomography (PET). Eight patients with soft tissue metastases were studied twice: before the onset of chemotherapy (4), hormonal therapy (3) or radiotherapy (1) and 3-14 weeks later. The radioactivity concentration of the low molecular weight fraction of venous plasma samples separated by fast gel filtration was used as input function. The input corrected uptake rate of 11C-methionine (Ki) in breast cancer metastases before the treatment ranged between 0.035 and 0.186 1 min-1 and the standardised uptake value (SUV) between 2.0 and 11.4. The uptake of 11C-methionine into the metastases decreased when clinical objective stability or regression of the metastases was later obtained and increased in cases where progressive disease was seen during treatment. We conclude that metabolic changes in the amino acid metabolism detected by PET precede the clinical response, and may be of clinical value in predicting the treatment response.

[18F]fluorodeoxyglucose uptake in tumors: kinetic vs. steady-state methods with reference to plasma insulin.

[18F]Fluorodeoxyglucose (FDG) uptake in noncerebral tumors is commonly reported as tissue radioactivity concentration normalized to injected dose and body weight. We studied the feasibility of this approach by imaging 68 tumors in 46 oncologic patients with dynamic FDG-PET and compared kinetic and static methods of quantitation of FDG uptake. Further, the effect of plasma glucose and insulin concentration on the obtained quantitative indexes was analyzed in all patients. The metabolic rate for FDG was strongly associated with normalized uptake value adjusted for injected dose (r = 0.92, p < 0.0001), dose and patient weight (r = 0.91, p < 0.0001), and dose and body surface area (r = 0.94, p < 0.0001). The FDG uptake was not related to plasma glucose concentration under euglycemic (< or = 6.5 mmol/L) conditions, but was low in two diabetic patients with overt hyperglycemia. Hyperinsulinemia was associated with a low to moderate FDG uptake, probably exerting its action through a metabolic shift of tracer influx to muscle and fat. Our results show that a single scan in the steady-state phase, e.g., 45-60 min from the injection, can be used for assessment of FDG uptake in tumors, making frequent blood sampling during imaging unnecessary. However, glucose concentration in blood must be monitored in patients with known or suspected abnormalities in glucose metabolism.

Influence of the blood glucose concentration on FDG uptake in cancer--a PET study.

Radiolabeled [11F]-2-fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue widely used to study tumor metabolism by means of positron emission tomography (PET). Little is known about the effect of hyperglycemia on FDG uptake and PET imaging of tumors. Five patients with head and neck cancer underwent two PET studies prior to cancer therapy, first in the fasting state and then 2-5 days later after oral glucose loading. FDG uptake was measured with standardized uptake values (SUV) and Ki values according to Patlak et al. The fasting SUVs ranged from 4.1 to 10.9 and Kis from 0.021 min-1 to 0.067 min-1, whereas after loading both the SUVs (range 2.2-5.9, p < 0.02) and Ki values (range 0.006-0.042 min-1, p < 0.05) decreased significantly, and the quality of the PET images became markedly poorer. The FDG metabolic rate (Ki x P-Gluc) remained similar in different plasma glucose concentrations in tumors, but increased clearly in muscles after loading. Therefore, patients entering PET-FDG studies should fast and their blood glucose concentration needs to be taken into account when evaluating FDG accumulation.

Carbon-11-methionine and PET is an effective method to image head and neck cancer.

Methionine metabolism is altered in cancer, and methionine labeled with 11C has been successfully used for imaging of brain, lung, and breast cancer and lymphoma. Uptake of L-[methyl-11C]methionine (11C-methionine) in head and neck cancer of 23 patients was studied with PET. Accumulation of 11C-methionine in the tumors was assessed by two different methods: the influx constant, Ki, and the standardized uptake value (SUV). All 23 cancers accumulated 11C-methionine. The mean Ki was 0.147 +/- 0.070 min-1 and the mean SUV 8.5 +/- 3.5. There was a strong correlation between the two measures of tumor uptake (r = 0.92, p less than 0.0001). There was no correlation between the uptake of 11C-methionine and the histological grade of cancer. Head and neck cancer can thus be effectively imaged with 11C-methionine. Carbon-11-methionine PET imaging may be useful in delineating tumors for therapy planning.

[11C]methionine quantitation in cancer PET studies.

Quantitation of the uptake of positron emitting tracers in cancer patients is still unsettled. A uniform method is needed for comparison of results and for collecting a data base of tumor PET studies. We have measured the tumoral uptake of [11C]methionine in 46 cancer patients using four different methods of analysis. The accumulation of [11C]methionine at 35-40 min after the injection adjusted to the injected dose and body surface area turned out to give similar results as a more complicated method where the uptake rate of [11C]methionine from the plasma to the tumor was calculated (r = 0.92, p less than 0.0001). The results suggest that in clinical [11C]methionine PET studies, 40 min emission scanning with frequent blood sampling is unnecessary. Only a single 5 min emission scan 25-40 min after the injection is required for analysis if the accumulation is adjusted to the injected dose and body surface area.

Uptake of 11C-methionine in breast cancer studied by PET. An association with the size of S-phase fraction.

L-[methyl-11-C]methionine (11C-methionine) uptake of seven primary breast cancers, four soft tissue metastases of breast cancer, and three other breast lesions was studied by positron emission tomography (PET). 11C-methionine accumulation was assessed by calculating the standardised uptake value (SUV). The mean SUV for breast cancer was 8.5 +/- 3.3 (s.d.), while the maximal uptake in the liver was 12.4 +/- 1.6, in the bone marrow 5.8 +/- 0.7, and in the myocardium 3.4 +/- 0.6. All eight malignant tumours larger than 30 mm in diameter accumulated clearly 11C-methionine, whereas none of the three smaller cancers (from 12 to 15 mm in diameter) were visualised. Strong uptake of 11C-methionine was associated with a large S-phase fraction (SPF) measured with flow cytometry (r = 0.77, P = 0.01), and the non-visualised cancers had all a small SPF (less than 5.5%). One benign tumour (an abscess) accumulated slightly 11C-methionine. The results indicate that both primary and metastatic breast cancer can be effectively imaged with 11C-methionine by PET, and that the accumulation of 11C-methionine may correlate with the proliferation rate of breast carcinoma.

Uptake of carbon-11-methionine and fluorodeoxyglucose in non-Hodgkin's lymphoma: a PET study.

Uptake of L-[methyl-11C]methionine (11C-methionine) and [18F]-2-fluoro-2-deoxy-D-glucose (FDG) was studied with PET in 14 patients with non-Hodgkin's lymphomas. The low molecular weight fraction of venous plasma separated by fast gel filtration was used as the input function for 11C-methionine studies, and tracer accumulation was analyzed according to Patlak and Gjedde. The average uptake rate of 11C-methionine was 0.0775 +/- 0.0245 min-1 (s.d.) and of FDG 0.0355 +/- 0.0293 min-1, 11C-methionine uptake rate being significantly higher than that of FDG (p less than 0.01). Carbon-11-methionine accumulated strongly in all but one of the lymphomas. FDG accumulated clearly in lymphomas of high-grade malignancy, whereas two intermediate- and three low-grade malignant lymphomas had a poor uptake rate. The tumor/plasma ratio of both 11C-methionine and FDG increased faster in high and intermediate-grade lymphomas than in low-grade lymphomas, but there was considerable overlap between the histologic grades. Carbon-11-methionine seems to be preferable in detecting tumors, while FDG was superior to 11C-methionine in distinguishing the high-grade malignant lymphomas from the other grades.