Static PET Images Research Articles

Dynamic Small-Animal PET Imaging of Tumor Proliferation with 3′-Deoxy-3′-18F-Fluorothymidine in a Genetically Engineered Mouse Model of High-Grade Gliomas

3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), a partially metabolized thymidine analog, has been used in preclinical and clinical settings for the diagnostic evaluation and therapeutic monitoring of tumor proliferation status. We investigated the use of (18)F-FLT for detecting and characterizing genetically engineered mouse (GEM) high-grade gliomas and evaluating the pharmacokinetics in GEM gliomas and normal brain tissue. Our goal was to develop a robust and reproducible method of kinetic analysis for the quantitative evaluation of tumor proliferation. Dynamic (18)F-FLT PET imaging was performed for 60 min in glioma-bearing mice (n = 10) and in non-tumor-bearing control mice (n = 4) by use of a dedicated small-animal PET scanner. A 3-compartment, 4-parameter model was used to characterize (18)F-FLT kinetics in vivo. For compartmental analysis, the arterial input was measured by placing a region of interest over the left ventricular blood pool and was corrected for partial-volume averaging. The (18)F-FLT "trapping" and tissue flux model parameters were correlated with measured uptake (percentage injected dose per gram [%ID/g]) values at 60 min. (18)F-FLT uptake values (%ID/g) at 1 h in brain tumors were significantly greater than those in control brains (mean +/- SD: 4.33 +/- 0.58 and 0.86 +/- 0.22, respectively; P < 0.0004). Kinetic analyses of the measured time-activity curves yielded independent, robust estimates of tracer transport and metabolism, with compartmental model-derived time-activity data closely fitting the measured data. Except for tracer transport, statistically significant differences were found between the applicable model parameters for tumors and normal brains. The tracer retention rate constant strongly correlated with measured (18)F-FLT uptake values (r = 0.85, P < 0.0025), whereas a more moderate correlation was found between net (18)F-FLT flux and (18)F-FLT uptake values (r = 0.61, P < 0.02). A clinically relevant mouse glioma model was characterized by both static and dynamic small-animal PET imaging of (18)F-FLT uptake. Time-activity curves were kinetically modeled to distinguish early transport from a subsequent tracer retention phase. Estimated (18)F-FLT rate constants correlated positively with %ID/g measurements. Dynamic evaluation of (18)F-FLT uptake offers a promising approach for noninvasively assessing cellular proliferation in vivo and for quantitatively monitoring new antiproliferation therapies.

FDG-PET imaging for the staging and follow-up of small cell lung cancer.

The staging procedures for small cell lung cancer do not differ appreciably from those for other forms of lung cancer. For practical purposes, the TNM stages are usually collapsed into a simple binary classification: limited disease and extensive disease. This study was performed to answer the question of whether fluorine-18 labelled 2-deoxy-2-D-glucose positron emission tomography (FDG-PET) imaging permits appropriate work-up (including both primary and follow-up staging) of patients presenting with small cell lung cancer, as compared with currently recommended staging procedures. Thirty-six FDG-PET examinations were performed in 30 patients with histologically proven small cell lung cancer. Twenty-four patients were examined for primary staging while four were imaged for therapy follow-up only. Two patients underwent both primary staging and up to four examinations for therapy follow-up. Static PET imaging was performed according to a standard protocol. Image reconstruction was based on an ordered subset expectation maximization algorithm including post-injection segmented attenuation correction. Results of FDG-PET were compared with those of the sum of other staging procedures. Identical results from FDG-PET and the sum of the other staging procedures were obtained in 23 of 36 examinations (6x limited disease, 12x extensive disease, 5x no evidence of disease). In contrast to the results of conventional staging, FDG-PET indicated extensive disease resulting in an up-staging in seven patients. In one patient in whom there was no evidence for tumour on conventional investigations following treatment, FDG-PET was suggestive of residual viability of the primary tumour. Furthermore, discordant results were observed in five patients with respect to lung, bone, liver and adrenal gland findings, although in these cases the results did not affect staging as limited or extensive disease. Moreover, FDG-PET appeared to be more sensitive for the detection of metastatic mediastinal and hilar lymph nodes and bone metastases. Finally, all findings considered suspicious for tumour involvement on the other staging procedures were also detected by FDG-PET. It is concluded that FDG-PET has potential for use as a simplified staging tool for small cell lung cancer.

Preliminary assessment of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with bladder cancer.

The purpose of this study was to assess the feasibility of imaging of bladder cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning. We studied 12 patients with histologically proven bladder cancer who had undergone surgical procedures and/or radiotherapy. Retrograde irrigation of the urinary bladder with 1000-3710 ml saline was performed during nine of the studies. Dynamic and static PET images were obtained, and standardized uptake value images were reconstructed. FDG-PET scanning was true-positive in eight patients (66.7%), but false-negative in four (33.3%). Of 20 organs with tumor mass lesions confirmed pathologically or clinically, 16 (80%) were detected by FDG-PET scanning. FDG-PET scanning detected all of 17 distant metastatic lesions and two of three proven regional lymph node metastases. FDG-PET was also capable of differentiating viable recurrent bladder cancer from radiation-induced alterations in two patients. In conclusion, these preliminary data indicate the feasibility of FDG-PET imaging in patients with bladder cancer, although a major remaining pitfall is intense FDG accumulation in the urine.

Pathophysiological Basis and Clinical Value of &lt;sup&gt;18&lt;/sup&gt;F-Fluorodeoxyglucose and Positron Emission Tomography in Pancreatic Adenocarcinoma

2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of pancreatic cancer was evaluated and compared to CT scan. Also the glucose transporter 1 (Glutl) encoding gene expression was determined by Northern blot analysis in 7 patients with pancreatic cancer (PC) and 5 patients with chronic pancreatitis (CP). 73 patients with suspected PC or CP underwent static PET imaging after injection of 250-350 MBq FDG. Focal FDG uptake was considered a sign of malignancy and was calculated using standardized uptake values (60 min p.L). Increased Glutl expression could be demonstrated in all patients with PC and not in patients with CP indicating an important contribution of Glutl to enhanced tumoral glucose consumption. In the visual FDG-PET analysis 41/43 (95%) patients with histologically controlled PC and 27/39 (90%) patients with CP were classified correctly by PET. With CT 33/41 (80%) patients with PC were diagnosed correctly, whereas 7/27 were false-positive (specificity 74%). Thus FDG-PET provided a reliable differentiation of pancreatic adenocarcinoma from chronic pancreatitis.