A. Dimitrakopoulou

Perfusion of colorectal liver metastases and uptake of fluorouracil assessed by H215O and [18F]uracil positron emission tomography (PET)

Perfusion and fluorouracil (FU) accumulation were assessed using positron emission tomography (PET) with H2(15)O and 18FU in 36 patients with colorectal liver metastases. The tracers were injected intravenously and via the hepatic artery. Standard uptake values (SUV) were calculated using a region of interest (ROI) technique. The perfusion of non-tumorous liver tissue was similar after intravenous (i.v.) and intra-arterial (i.a.) assessment [mean of 2.67 (s = 0.61) and 2.2 (s = 0.45)]. Metastases were found to be hypoperfused compared to normal liver tissue after i.v. examinations [mean 1.73 (s = 0.77)]; i.a. injections revealed greater perfusion in metastases [mean 6.41 (s = 5.47)]. Single metastases showed up to 10 times greater perfusion with the i.a. injection route than with the i.v. one. However, lesions with no change or lower perfusion were also observed. Generally, accumulation of 18FU in metastases after i.v. infusion was less than after i.a.. Correlation of i.v. perfusion and uptake was moderate (r = 0.54, P = 0.0001); i.a. correlation was only slightly better (r = 0.61, P = 0.008). Perfusion as measured by H2(15)O-PET does not generally predict uptake of 18FU in colorectal liver metastases. To measure FU uptake using PET and 18F seems to be the most accurate method. It would allow one to identify individual patients with considerably greater accumulation of 18FU following i.a. administration who should profit from a cross-over to intrahepatic chemotherapy.

Positron Emission Tomography Measurement of Fluorouracil Uptake Prior to Therapy and Chemotherapy Response

The standard chemotherapeutic agent for the treatment of hepatic metastases from colorectal cancer is 5-fluorouracil (FU) [1]. Depending on both the selection process and the response criteria used, the reported response rates have varied from 8% to 82% [1]. Based on a literature survey, Kemeny reported that the average response rate for liver metastases was 23% [1]. The metabolism of FU has been studied and was recently summarized by Hull et al. [2]. These authors found no significant difference in the metabolite concentrations in plasma between responders and nonresponders to FU chemotherapy. They state that the detection of FU metabolites in tumor tissue is required for an assessment of response to FU. Shani and Wolf showed in an animal study that drug-responsive tumors had a 20: 1 tumor-to-blood ratio 12 h after injection, while drug-resistant tumors had only a 4:1 ratio [3]. These data indicate that FU metabolite measurements in tumor tissue may be helpful in predicting response to FU chemotherapy in patients.

Positron Emission Tomography with Fluorodeoxyglucose for the Evaluation of Tumor Recurrence of Thoracic Tumors

The detection of recurrent tumors of thoracic lesions has remained a difficult diagnostic challenge despite the great advances seen in computed tomography (CT) and magnetic resonance imaging (MRI). The common differential diagnostic problem of distinguishing tumor recurrence from scar or inflammatory tissue has increasingly become a difficult clinical problem. Since therapeutic approaches are available in cases of recurrences, a timely and correct diagnosis becomes of increasing importance. The morphologic evaluation of suspect regions of tumor recurrences is quite limited especially if the size of the lesion is still small. Therefore additional information in conjunction with its morphologic information is needed. Positron emission tomography (PET) using metabolically active compounds, such as flour-18 labelled deoxyglucose (FDG) allow imaging of metabolism [1]. As clinical studies to evaluate the potential use of FDG PET imaging for thoracic lesions have shown a great potential benefits [2, 3], this technique is being introduced for the evaluation of recurrent tumors. Two considerations of great importance in the evaluation of recurrent tumors by PET are changes in the metabolic state and function of lesions due to the previous therapy and secondarily due to therapeutic procedures, which may have altered the cross-sectional anatomy. A very careful correlation between the morphologic cross-sectional information obtained by CT and MRI with the functional cross-sectional information available by PET is necessary.

[18F]fluorodeoxyglucose Uptake for the Measurement of Metabolic Therapy Effects in a Mammary Carcinoma Model

The advantages of ether lipids are their relatively low systemic toxicity and their suitability for oral application [1]. In a clinical phase I study, hexadecylphosphocholine (HPC) was found to be effective in the topical treatment of skin metastases of breast cancer [2]. It is suggested that HPC is metabolized by phospholipase C to its active form [3]. However, the exact mechanism of action is not known. We performed in vivo studies of glucose uptake before and after therapy in a mammary carcinoma model to assess drug-induced changes in the glucose metabolism of these tumors.

Evaluation of Modulated Fluorouracil Chemotherapy with Positron Emission Tomography in Patients with Metastatic Colorectal Cancer

The standard chemotherapeutic agent for the treatment of hepatic metastases from colorectal cancer is 5-fluorouracil (FU) [1]. Depending on both the selection process and the response criteria used, the reported response rates have varied from 8% to 82% [1]. Based on a literature survey, Kemeny reported that the average response rate for hepatic metastases was 23%. The metabolism of FU has been studied extensively and was recently summarized by Hull et al. [2]. Therefore, modified treatment protocols including d, l-folinic acid have found use for therapy. Trave et al. demonstrated an increased inhibition of thymidilate synthase following pretreatment with d, l-folinic acid [3]. We examined patients with [18F]FU and positron emission tomography (PET) to obtain quantitative data about the distribution pattern of FU and metabolites in metastases, normal liver parenchyma, and aorta as a function of time. Our primary goal was to evaluate the effect of d, l-folinic acid pretreatment on the FU metabolite concentrations.

Evaluation of Regional Fluorouracil Chemotherapy in Patients with Metastatic Colorectal Cancer

The standard chemotherapeutic agent for the treatment of hepatic metastases from colorectal cancer is 5-fluorouracil (FU) [1]. Depending on both the selection process and the response criteria used, the reported response rates have varied from 8% to 82% [1]. Based on a literature survey, Kemeny reported that the average response rate for hepatic metastases is 23%. Therefore, the regional administration of FU has found use for improving the selectivity of the cytostatic drug [2]. Theoretically, regional delivery can potentially increase drug concentrations at tumor sites and lower systemic drug exposure when compared with systemic drug administration. We examined patients with 18F-labeled FU and positron emission tomography (PET) to obtain quantitative data about the distribution pattern of FU and metabolites in metastases, normal liver parenchyma, and aorta as a function of time. Furthermore, 15O-labeled water was used to determine the relative perfusion of the lesions, and we compared the absorption of the non-metabolized tracer with the metabolized cytostatic drug. Our primary goal was to evaluate the tracer concentrations following intravenous and intraarterial infusion of FU. Furthermore, we compared the change in perfusion due to regional administration with the altered FU accumulation.

Optimized Therapy Management in Unresectable Bronchogenic Carcinoma by Fluorodeoxyglucose Positron Emission Tomography

The increasing number of different therapeutic protocols necessitates an early objective evaluation of therapy response. Depending on significant response to the ongoing therapy, the chosen protocol is continued, or alternative protocols are used. Current diagnostic imaging techniques, from conventional radiology to computed tomography and magnetic resonance imaging enable morphologic evaluation of therapy response, limited mainly by the change in tumor volume. Positron emission tomography (PET) with the use of metabolically active substances such as [18F]fluorodeoxyglucose (FDG) enables a direct quantification of the metabolic state with cross-sectional imaging of bronchogenic carcinoma. The technical basis of PET relies, as does that of CT, on computerized reconstruction of cross-sections. Positron-labeled radiopharmaceutical compounds emitted from the body are used as the source for PET images, while the attenuation of X-ray photons from an X-ray tube is used in computed tomography. Despite the fact that PET currently requires very large technical hardware, scanner, and cyclotron, patient studies can be performed in acceptable study times of 25–40 min without inconvenience to the patient due to noise or limited space.

Positron Emission Tomography: A Noninvasive Procedure for the Determination of Tumor Proliferation

Morphological parameters such as size are not sufficient for an accurate assessment of biological behavior in tumors. In contrast, the uptake of [18F]fluoro-2-deoxyglucose (FDG) has been found to be correlated with histological malignancy grading in brain tumors [1, 2]. Alavi et al. [3] proposed that these data be used to predict survival rates. Minn and coworkers [4] observed in a mixed tumor population a strong correlation between FDG uptake and the S-phase fraction and suggested FDG imaging as a noninvasive method to assess the proliferative activity of human cancers. We evaluated the relationship between glucose uptake and tumor proliferation rate in patients with squamous cell carcinomas (SCC).

Assessment of Tumor Metabolism in Liver Metastases Using Positron Emission Tomography and [18F] fluorodeoxyglucose

Metastatic malignant tumors of the liver are common in clinical practice, probably ranking second only to cirrhosis as a cause of fatal liver disease. Hepatic metastases have been reported at autopsies in 30%–50% of patients dying from malignant disease. Patients with metastatic liver involvement usually have imaging studies with ultrasound, computed tomography (CT), or magnetic resonance imaging. All these methods provide morphologic information about the malignant lesions, which are used for therapy management. Besides the morphologic data, functional information about the metabolism of metastases may enhance therapy planning. Therefore, we used positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) to assess whether PET gives additional information about the change in tumor metabolism before, during, and after chemotherapy in patients with metastatic colorectal carcinomas.

Monitoring of Combined Therapy in Advanced Head and Neck Cancer with Positron Emission Tomography and [18F]fluorodeoxyglucose

For the evaluation and individual planning of chemotherapy or head and neck tumors it is useful to obtain information about the tumor metabolism and its early changes during chemotherapy. Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) is a specific method that gives information about glucose uptake. These data can be used in follow-up studies to assess the effectiveness of a therapeutic schedule.