18F-labeled fluorouracil positron emission tomography and the prognoses of colorectal carcinoma patients with metastases to the liver treated with 5-fluorouracil

Abstract

BACKGROUND Although many factors have been investigated in connection with the prognoses of colorectal carcinoma patients with metastases to the liver, a means for evaluating response and prognosis prior to the administration of standard chemotherapy has not been available. Positron emission tomography (PET) is a noninvasive means of measuring the distribution of radiolabeled cytostatic agents in tumor regions. METHODS Prior to the administration of 5‐fluorouracil chemotherapy, the authors examined 14 colorectal carcinoma patients with unresectable liver metastases using a single PET scan and 18F‐labeled fluorouracil (18F‐FU). Clinical response and survival time were correlated with 18F‐FU uptake values (SUV) measured in liver metastases 120 minutes after tracer infusion. RESULTS Trapping of 18F‐FU varied even among different metastases in the same patient. The range of SUV was 0.9‐4.3 (mean, 2.20). Four patients with SUV exceeding 2.8 had stable disease for longer than 12 months and survived longer than 21 months. Three patients with SUV less than 1.2 had progressive disease and survived less than 12 months. The 6 patients with partial remission or stable disease had a mean SUV of 2.96 and a mean survival of 31.6 months. Eight patients with progressive disease had a mean SUV of 1.59 and a mean survival of 14.5 months (Student's t test, P < 0.012). In scatterplot analysis, there was a statistically significant correlation between SUV and survival time. CONCLUSIONS Patients with high 18F‐FU uptake values are more likely to achieve at least stabilization of disease with planned chemotherapy. 18F‐FU PET may be a valuable new tool for determining, prior to 5‐FU‐based chemotherapy, which patients are likely to have good responses and prolonged survival. Cancer 1998;83:245‐253. © 1998 American Cancer Society.

Integrating Dynamic Positron Emission Tomography and Conventional Pharmacokinetic Studies to Delineate Plasma and Tumor Pharmacokinetics of FAU, a Prodrug Bioactivated by Thymidylate Synthase

“…The process of integrating dynamic PET assessment into early-phase clinical trials to obtain information on drug distribution to normal and tumor tissues has been applied in the development of a number of anticancer drugs such as 5-FU, BCNU (an alkylating agent specific for brain tissue), DACA (a topoisomerase I/II inhibitor), and SMT487 (a somatostatin analogue). [20][21][22][23] However, the major barriers to the utility of dynamic PET for plasma and tissue PK evaluation are the short follow-up time of PET and its inability to distinguish the radiolabeled parent drug and metabolites. This study, for the first time to our best knowledge, presents a pharmacometric modeling approach to overcome these barriers by simultaneously modeling dynamic PET tissue data and long-term conventional plasma PK data.…”

Phase I feasibility study of Magnetic Resonance guided High Intensity Focused Ultrasound-induced hyperthermia, Lyso-Thermosensitive Liposomal Doxorubicin and cyclophosphamide in de novo stage IV breast cancer patients: study protocol of the i-GO study

“…Total bilirubin >1. 5 Open access ► Inability to lie in prone position. ► A medical or psychiatric condition or other circumstances which would significantly decrease the chances of understanding the informed consent process, obtaining reliable data, achieving study objectives or completing the study treatment and/or examinations.…”

“…5-fluorouracil and docetaxel. Higher tumour uptake of radio-active labelled 5-fluorouracil or docetaxel chemotherapy on positron emission tomography (PET) was shown to correlate, respectively, with longer survival in patients with liver metastasis of colorectal carcinoma 5 and with better tumour response in lung cancer patients. 6 In a study comparing different dose schedules of the adjuvant AC regimen, the highest dosages (60 mg/m 2 doxorubicin and 600 mg/m 2 cyclophosphamide) were most effective, and this is currently the standard of care.…”

Positron Emission Tomography as a Method for Measuring Drug Delivery to Tumors in vivo: The Example of [11C]docetaxel

“…As tumor response to anticancer drugs is thought to be directly related to drug concentrations in tumor tissue, uptake of radiolabeled anticancer drugs in tumors may predict treatment outcome. Preliminary PET studies using F-18 labeled 5-fluorouracil ([ 18 F]5-FU; (9, 10)), tamoxifen ([ 18 F]fluorotamoxifen; (11)), and C-11 labeled docetaxel ([ 11 C]docetaxel; (12)) showed that high tumor uptake of the radiolabeled anticancer drug was associated with improved tumor response following corresponding therapy. These studies suggest that radiolabeled anticancer drugs may be useful for prediction of outcome prior to start of treatment.…”

“…These studies suggest that radiolabeled anticancer drugs may be useful for prediction of outcome prior to start of treatment. Consequently, an increasing number of anticancer drugs has now been radiolabeled including radiolabeled cytotoxic agents (e.g., [ 11 C]temozolomide, [ 18 F]5-fluorouracil, and [ 11 C]docetaxel), selective hormone receptor modulators (e.g., [ 18 F]fluorotamoxifen), tyrosine kinase inhibitors (TKIs, e.g., N-[ 11 C]methylimatinib, [ 11 C]sorafenib, and [ 11 C]erlotinib), and monoclonal antibodies [Mabs, e.g., [ 89 Zr]cetuximab, [ 89 Zr]trastuzumab, and [ 89 Zr]bevacizumab; (10, 11, 13–20)].…”