Evaluation of tumor growth in vivo in a rat model of liver metastasis, using a newly devised index obtained by positron emission tomography with [18F] FDG

Background/Purpose [¹⁸F] fluorodeoxyglucose-positron emission tomography (FDG-PET) is regarded as a unique imaging modality, because the images reflect tumor activity. This characteristic of PET encouraged us to use it to develop a novel method of quantitatively measuring liver metastasis viability. Methods F344 rats were injected with rat colon adenocarcinoma cells (RCN-9 cell line) via the portal vein, and some of them were treated with 5-fluorouracil (5-FU). Tumor growth and tumor activity were measured by PET. We used a tumor viability index (TVI) to evaluate changes in tumor activity and to quantitatively evaluate tumor proliferation activity, instead of using the standardized uptake value (SUV) of the tumor tissue. The TVI was compared with the number of tumor nodules and the proliferating cell nuclear antigen (PCNA) index 28 days after RCN-9 cell inoculation. Results [¹⁸F] FDG uptake by the liver tumors was measured by PET, and the TVI was found to increase as the tumor nodules increased in number and size. The TVI values in the experimental model represented the viability of tumors suppressed by chemotherapy, and the values were significantly correlated with the number of nodules and the PCNA index. Conclusions The TVI was concluded to be superior to the SUV, the commonly used indicator, for evaluating tumor growth, especially that of multiple, small tumors.     

Association of the SUV39H1 histone methyltransferase with the DNA methyltransferase 1 at mRNA expression level in primary colorectal cancer

This study was aimed at investigating the involvement of the SUV39H1 histone methyltransferase on the epigenetic change of euchromatic promoter in colorectal cancer. We retrospectively analyzed the mRNA levels of SUV39H1 and the promoter methylation of the p14(ARF), p16(INK4a) and HLTF genes as well as the mRNA levels of DNA methyltransferase 1 (DNMT1) in fresh frozen tissues from 219 colorectal cancer patients. The mRNA levels of the SUV39H1 and DNMT1 were assessed via quantitative real-time PCR and the methylation profiles of the CpG islands were determined using methylation-specific PCR. The mRNA levels of SUV39H1 and DNMT1 were elevated in 25% and 42% of 219 colorectal cancers, respectively. The hypermethylation of the p14(ARF), p16(INK4a) and HLTF genes occurred in 36%, 51% and 34% of the patients. The elevated mRNA levels of SUV39H1 were not associated with the hypermethylation of the 3 genes. However, the mRNA levels of DNMT1 were significantly different between patients with elevated mRNA levels of SUV39H1 and those without (1.62 +/- 0.84, 0.91 +/- 0.81, respectively; p = 0.007). Patients with elevated mRNA levels of SUV39H1 showed a higher prevalence of DNMT1 elevation than those without (61 vs. 35%, p = 0.0008). Patients with an elevated mRNA level of SUV39H1 had a 2.71 (95% CI = 1.09-4.48, p = 0.002) times greater risk of an elevated mRNA level of DNMT1, after controlling for age and gender. In conclusion, the present study suggests that SUV39H1 is significantly associated with DNMT1, but not with euchromatic promoter methylation in colorectal cancer.     

SUV correction for injection errors in FDG-PET examination

Objective Many studies have documented the clinical usefulness of standardized uptake values (SUV) for diagnosis. However, in the event of injection error, accurate measurements cannot be obtained if the radioactivity of fluorodeoxyglucose (FDG) leakage is not subtracted from the administered dosage. Here, a correction formula for radioactivity estimation that takes into account the radioactivity of FDG leakage was derived on the basis of a phantom experiment. Furthermore, to determine whether SUV could be accurately calculated by the correction formula, we performed a volunteer study. Methods Images were displayed by altering the conversion constant from 1.0, 0.1 to 0.01, and the range of correctable counts was verified on the basis of image inversion. To estimate the radioactivity of FDG leakage by imaging, the count of the leakage was measured, converted into a radioactivity concentration using a cross-calibration factor (CCF), and multiplied by volume, as measured by imaging. Three factors that markedly affect count, i.e., count rate performance, partial volume effect and crosstalk, were assessed in phantom studies in order to derive a correction formula. In addition, to clarify the accuracy of the correction formula, we attached to the right elbow. Results With a conversion constant of 0.1, there was no image inversion at ≤1.565 MBq/ml. At concentrations below this, the average detection rate was 90%. This suggests that count rate performance can be corrected at ≤1.0 MBq/ml. Crosstalk investigations clarified that the effects of adjacent radioactivity concentrations on FDG leakage were not marked. On the basis of investigations on partial volume effect and count rate performance, the following formulas were derived: For leakages of ≥28 mm Leakage radioactivity (MBq) = positron emission tomography (PET) radioactivity (MBq) × 0.9. For leakages of ≥15 mm but <28 mm Leakage radioactivity (MBq) = PET radioactivity (MBq) × 0.9 × (0.0517 × leakage size (mm) − 0.4029). In a volunteer study with 10 MBq leakage, SUV recalculated using the formula achieved 99.97% correction, whereas with 100 MBq leakage, SUV achieved 67.5% resulting in poor correction. Conclusions The present correction technique can accurately calculate SUV and could be useful for the clinical diagnosis of malignant tumors.     

Detection of local residual tumor after laryngeal cancer treatment using FDG-PET

OBJECTIVE: Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is sometimes used as a means of follow-up after diagnosis and treatment of cancers of the head and neck region. The present study was undertaken to evaluate the ability of FDG-PET to detect local residual tumor after treatment of laryngeal cancer. METHODS: Thirty-six patients with laryngeal cancer underwent FDG-PET before and after initial treatment. Of these patients, 20 received FDG-PET before treatment and 28 received it after treatment. The relationship between standardized uptake values (SUV) and the presence or absence of local residual tumor was investigated by setting the cut-off value of the SUV using the receiver operating characteristics (ROC) curve. RESULTS: When the pre-treatment SUV threshold for laryngeal cancer was set at 7.20, the detection of local residual tumor after treatment using FDG-PET had a sensitivity of 77.78%, specificity of 81.82%, false positive rate of 18.18%, false negative rate of 22.22%, accuracy of 80% and a p value of 0.02. When the post-treatment SUV threshold for the larynx was set at 3.35, the test had a sensitivity of 93.75%, specificity of 91.67%, false positive rate of 8.33%, false negative rate of 6.25%, accuracy of 92.86% and a p value of 0.0001. CONCLUSIONS: FDG-PET was found to be useful for determining the presence of local residual tumor after treatment of laryngeal cancer.     

Fluorodeoxyglucose positron emission tomography (FDG-PET) for monitoring lymphadenopathy in the autoimmune lymphoproliferative syndrome (ALPS)

Autoimmune lymphoproliferative syndrome (ALPS) is associated with mutations that impair the activity of lymphocyte apoptosis proteins, leading to chronic lymphadenopathy, hepatosplenomegaly, autoimmunity, and an increased risk of lymphoma. We investigated the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in discriminating benign from malignant lymphadenopathy in ALPS. We report that FDG avidity of benign lymph nodes in ALPS can be high and, hence, by itself does not imply presence of lymphoma; but FDG-PET can help guide the decision for selecting which of many enlarged nodes in ALPS patients to biopsy when lymphoma is suspected.     

Positron emission tomographic imaging with<Superscript>11</Superscript>C-choline in differential diagnosis of head and neck tumors: comparison with<Superscript>18</Superscript>F-FDG PET

The aim of this study was to evaluate the clinical value of positron emission tomography (PET) with¹¹C-labeled choline (CHOL) for the differential diagnosis of malignant head and neck tumors from benign lesions as compared with¹⁸F-fluorodeoxyglucose PET.Methods: We studied 45 patients (28 males, 17 females, age range, 29-84 years) with suspected lesions in the head and neck region using both CHOL and FDG PET within a 2-week period on each patient. All patients fasted for at least 6 hours for both the CHOL and FDG studies. PET imaging was performed 5 min and 50-60 min after intravenous injection of CHOL and FDG, respectively. After data acquisition, PET images were corrected for attenuation, and the reconstructed images were analyzed by visual interpretation. Then, the standardized uptake value (SUV) was calculated for semiquantitative evaluation of tumor tracer uptake. Finally the results of PET scans were compared with the histological diagnoses from surgical specimens or biopsies.Results: With CHOL PET, malignant tumors were correctly detected in 24 (96%) of 25 patients, and benign lesions in 14 (70%) of 20 patients with an accuracy of 84.4%. With FDG PET, malignancy was correctly diagnosed in 23 (92%) of 25 patients, and benign lesions in 13 (65%) of 20 patients resulting an accuracy of 80%. A significant positive correlation between CHOL and FDG SUVs was found for all lesions (r = 0.677, p = 0.004, n = 45). Malignant tumors showed significantly higher tracer accumulation than the benign lesions in both CHOL and FDG studies (5.69 ± 1.61, n = 25 vs. 2.98 ± 2.13, n = 20, p < 0.0001; 9.21 ± 4.23, n = 25 vs. 3.60 ± 2.57, n = 20, p < 0.0001). The cutoff SUV for differentiating malignant and benign lesions was 3.5 for CHOL and 3.9 for FDG. CHOL showed slightly better differentiation between malignant and benign lesions than FDG although some overlap existed on both studies. But the difference was not statistically significant.Conclusion: The results of this study indicate that CHOL PET may be feasible clinically for head and neck tumor imaging. PET imaging with CHOL seems to be able to detect malignant head and neck tumors as effectively as FDG PET. The advantages of CHOL PET were shorter examination period and low uptake in the muscle. However, both CHOL and FDG have some limitations in the evaluation of salivary gland lesions.     

90Y microsphere treatment of unresectable liver metastases: changes in 18F-FDG uptake and tumour size on PET/CT

Purpose The intra-arterial administration of ⁹⁰Y microspheres is a new palliative treatment option for unresectable liver metastases. The aim of this study was to quantitatively assess changes in FDG uptake and tumour size following ⁹⁰Y microsphere treatment (SIR-Spheres) using ¹⁸F-fluorodeoxyglucose (FDG) PET/CT imaging.Methods Five patients with unresectable liver metastases who had failed multiple prior chemotherapy regimens received seven ⁹⁰Y microsphere treatments to a single liver lobe. All patients underwent a baseline PET/CT scan prior to treatment, as well as up to four follow-up PET/CT scans. The tumour area of 30 liver metastases was measured on CT and the FDG uptake was semiquantitatively assessed by calculation of standardised uptake values (SUVs). A total of 18 FDG-PET/CT scans were performed.Results The SUVs in the 30 treated liver metastases decreased from 6.5±2.3 at baseline to 4.2±1.8 after the first follow-up PET/CT scan (p=0.001). In contrast, the SUVs of untreated metastases increased slightly from 7.2±2.3 to 8.0±0.8. There was no difference in FDG uptake in treated versus untreated normal liver tissue. Using a previously defined threshold of 20% decrease in SUV from baseline to determine response, 20 out of 30 liver metastases were considered to have responded at the first follow-up PET/CT scan approximately 1 month after treatment. In these metastases, the SUV decreased by 47±12%, compared with a slight increase by 5.9±19% in ten non-responding metastases (p=0.0001). The changes in tumour size did not correlate with changes in FDG uptake. On the first follow-up PET/CT scan, the tumour area on CT increased by 3.1±57% in treated metastases compared with 23.3±32% in untreated metastases. A wide range of post-treatment changes of target lesions was observed on CT, including an increase in the size of hypodense lesions, necrotic features and complete resolution of CT abnormalities.Conclusion The metabolic information obtained from FDG-PET/CT seems to provide a more accurate and earlier assessment of therapy response following ⁹⁰Y microsphere treatment than does the anatomical CT information.