Takayoshi Ishimori

Diagnosis of pancreatic cancer using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) --usefulness and limitations in "clinical reality".

The present review will provide an overview of the literature concerning the FDG PET diagnosis of pancreatic cancer and a summary from our experience of 231 cases of pancreatic lesions. FDG PET can effectively differentiate pancreatic cancer from benign lesion with high accuracy. Newlydeveloped PET scanners can detect small pancreatic cancers, up to 7 mm in diameter, by their high resolution, which could make a great contribution to the early detection of resectable and potentially curable pancreatic cancers. FDG PET is useful and cost-beneficial in the pre-operative staging of pancreatic cancer because an unexpected distant metastasis can be detected by whole-body PET in about 40% of the cases, which results in avoidance of unnecessary surgical procedures. FDG PET is also useful in evaluation of the treatment effect, monitoring after the operation and detection of recurrent pancreatic cancers. However, there are some drawbacks in PET diagnosis. A relatively wide overlap has been reported between semiquantitative uptake values obtained in cancers and those in inflammatory lesions. As for false-positive cases, active and chronic pancreatitis and autoimmune pancreatitis sometimes show high FDG accumulation and mimic pancreatic cancer with a shape of focal uptake. There were 8 false negative cases in the detection of pancreatic cancer by FDG PET, up to 33 mm in diameter, mainly because of their poor cellularity in cancer tissues. In addition, there are 19% of cancer cases with a decline in FDG uptake from 1 hr to 2 hr scan. FDG PET was recently applied to and was shown to be feasible in the differential diagnosis of cystic pancreatic lesions, such as intraductal papillary mucinous tumor of the pancreas. Further investigations are required to clarify the clinical value of FDG PET in predicting prognosis of the pancreatic patients.

Clinical value of FDG-PET in the follow up of post-operative patients with endometrial cancer

Objective: The clinical usefulness of FDG-PET in the follow up of post-operative patients with endometrial cancer was retrospectively evaluated.Methods: Twenty-one post-operative patients with endometrial cancer received 30 FDG-PET examinations to evaluate recurrence or response to treatment. The findings of FDG-PET were compared with their serum levels of tumor markers, CT and/or MRI findings, and the final outcome. Results of FDG-PET were also correlated with the clinical course of each patient.Results: In detecting recurrent lesions and evaluating treatment responses, FDG-PET, with the help in anatomic information by CT/MRI, showed better diagnostic ability (sensitivity 100.0%, specificity 88.2%, accuracy 93.3%) compared with combined conventional imaging (sensitivity 84.6%, specificity 85.7%, accuracy 85.0%) and tumor markers (sensitivity 100.0%, specificity 70.6%, accuracy 83.3%). FDG-PET had no false-negative results, suggesting the possibility of its use as the first-line examination in a patient’s follow-up. FDG-PET could detect unknown lesions in 4 cases, and, as reported for other malignancies, FDG-PET affected the patient management in one-third of the cases. Furthermore, the results of FDG-PET correlated well with the clinical outcome of the patients, with patients with negative PET results tending to show disease-free courses.Conclusions: These results suggest that, despite the limited number of patients studied, FDG-PET was accurate in detecting recurrence and evaluating therapeutic response, and could afford important information in the management of post-operative patients with endometrial cancer. FDG-PET also appeared to have a possibility to predict the outcome of each patient.

18F-FDG and11C-methionine PET for evaluation of treatment response of lung cancer after stereotactic radiotherapy

This study was performed to investigate the feasibility of FDG- and L-[methyl-11C]methionine (Met)-PET for the follow up of lung cancer after stereotactic radiotherapy (SRT). Nine patients (pt) with solitary lung cancer underwent SRT. Met- and FDG-PET studies were performed one week before SRT and from one week to 8 months after SRT. Responses to SRT were complete in 2 pt and partial in 7 pt. Met- and FDG-PET scan showed high tracer uptake in all tumors before SRT. After SRT, standardized uptake values (SUV) of FDG and Met changed concordantly. Both decreased with time in 5 pt but did not decrease steadily in 4 pt, where 2 pt showed an increase at 1 to 2 weeks after SRT and 2 pt showed an increase at more than 3 months after SRT. The former appears to reflect the acute reaction to SRT and the latter radiation-induced pneumonitis. Although the addition of Met-PET did not provide additional information over FDG-PET, FDG- and Met-PET could be used to evaluate the treatment effect of SRT.

Effect of Nicotine and Ephedrine on the Accumulation of 18F-FDG in Brown Adipose Tissue

This study evaluated the effect of various β-adrenergic agonists on 18F-FDG uptake in brown adipose tissue (BAT) in rats using ex vivo biodistribution studies. Methods: Caffeine (10 mg/kg of body weight, n = 4), ephedrine (5 mg/kg of body weight, n = 4), nicotine (0.8 mg/kg of body weight, n = 9), or a mixture of nicotine and ephedrine (0.8 mg/kg of body weight and 5 mg/kg of body weight, respectively, n = 9) was injected into the peritoneal cavity of female Lewis rats 30 min before intravenous 18F-FDG injection. One hour after injection of 18F-FDG, the animals were sacrificed, and BAT, other major organs, and blood were extracted. The biodistribution results were compared with body temperature data. Results: In the rats injected with nicotine or ephedrine, the mean uptake of 18F-FDG, in percentage injected dose (%ID)/(g of interscapular BAT) × (kg of body weight), was significantly increased (7.9-fold for nicotine and 3.7-fold for ephedrine), compared to the control rats. Nicotine had the strongest effect on 18F-FDG uptake in BAT. Caffeine increased BAT uptake slightly, but this increase did not reach statistical significance. The combination of nicotine and ephedrine increased the uptake 12.0-fold, compared with control rats; more than either nicotine or ephedrine alone. Uptake of 18F-FDG in most other major organs did not change significantly. The effect of nicotine was blocked by prior injection of β-adrenergic antagonists. A transient decrease in body temperature was observed in the nicotine-injected group, and this effect was canceled by prior injection of β-adrenergic antagonists. No significant change in baseline temperature was seen before or after β-adrenergic agonist injection. Conclusion: Nicotine caused a greater increase in 18F-FDG uptake in BAT than did other interventions, and the effect was increased when nicotine was combined with ephedrine. The effect of nicotine was completely blocked by prior injection of β-adrenergic antagonists, indicating that β-adrenergic agonists increase the metabolism of BAT. These preclinical data suggest that patients should avoid nicotine and ephedrine before undergoing 18F-FDG PET to minimize 18F-FDG uptake in BAT.

3D MR angiography of intratumoral vasculature using a novel macromolecular MR contrast agent

Noninvasive methods to visualize blood flow in the intratumoral vasculature have not previously been studied. In the present study, the use of a novel intravascular MR contrast agent with a generation‐6 polyamidoamine dendrimer core (G6‐(1B4M‐Gd)192; MW: 175kD) was investigated, and the vasculature in experimental tumors was visualized using 3D MR angiography (MRA). Xenografted tumors in nude mice of two different histologies—KT005 (human osteogenic sarcoma) and LS180 (human colon carcinoma)—were used to obtain 3D MRA using G6‐(1B4M‐Gd)192 and Gd‐DTPA. The contrast MR sectional images were correlated with the corresponding histological sections. The intratumoral vasculature in the KT005 tumor was clearly visualized by 3D MRA, which became more evident with the growth of the tumor xenograft. In contrast, the intratumoral vasculature in the LS180 tumor was sparser and much less developed than that in KT005 tumors. Blood vessels with a diameter as small as 100 μm based on histology were visualized using 0.033 mmol Gd/kg of G6‐(1B4M‐Gd)192. In conclusion, intratumoral vasculature with a 100‐μm diameter was visualized better using 3D MRA with G6‐(1B4M‐Gd)192 than with Gd‐DTPA. Magn Reson Med 46:579–585, 2001.

Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core: Accelerated renal excretion with coinjection of lysine

One of the major limitations to macromolecular MRI contrast agents (MRI‐CAs) is their slow clearance and associated decreased excretion of gadolinium (Gd(III)). The effect of coinjecting lysine to accelerate renal excretion of a macromolecular MRI‐CA (generation‐4 PAMAM™ dendrimer (G4D‐(1B4M‐Gd)64)) was investigated. The biodistribution and urine and fecal excretion in athymic mice was evaluated with and without lysine coinjection. 3D‐dynamic‐micro‐MRI with G4D‐(1B4M‐Gd)64 was obtained with and without lysine coinjection, and the serial signal intensity (SI) change in the blood and organs was evaluated. When lysine was coinjected, urinary excretion of G4D‐(1B4M‐Gd)64 increased 5.4‐fold compared to that without lysine, resulting in decreased renal accumulation of G4D‐(1B4M‐Gd)64 from 150% to 40% injected dose per gram (P < 0.001). On dynamic MRI with G4D‐(1B4M‐Gd)64, when lysine was coinjected, the kidney‐to‐blood SI ratio was significantly lower than that obtained without lysine (P < 0.001). When lysine was coinjected, the G4D‐(1B4M‐Gd)64 was excreted from the kidney intact. Magn Reson Med 46:457–464, 2001.

Detection and localization of prostate cancer with the targeted biopsy strategy based on ADC Map: A prospective large-scale cohort study

To investigate the usefulness of targeted biopsy strategy based on apparent diffusion coefficient (ADC) maps in the detection and localization of prostate cancer.

Diffusion‐weighted magnetic resonance imaging in the detection of testicular torsion: Feasibility study

To investigate the feasibility and usefulness of diffusion‐weighted magnetic resonance imaging in the detection of testicular torsion.

Differential Uptake of 18F-fluorodeoxyglucose by Experimental Tumors Xenografted into Immunocompetent and Immunodeficient Mice and the Effect of Immunomodification

PURPOSE To study the contribution of immunologic background to the uptake of fluorine-18-fluorodeoxyglucose ((18)F-FDG) by the tumor tissues. METHODS The uptakes of (18)F-FDG to the same experimental tumor model (SCCVII) xenografted into immunocompetent and immunodeficient (athymic) mice were compared. In addition, the immunomodifying effect of steroid on the uptake of (18)F-FDG by these tumors was investigated. RESULTS The uptake of (18)F-FDG by the tumors in immunocompetent mice was significantly higher than that in immunodeficient (athymic) mice. Although steroid pretreatment had no effect on the tumor uptake in immunodeficient mice, it significantly decreased the tumor uptake in immunocompetent mice. CONCLUSION The higher tumor uptake of (18)F-FDG observed in immunocompetent mice, modulated by steroid pretreatment, was contributed by the host immune reaction, probably cellular immunity employed by T-lymphocytes. These findings can clinically conclude that the intense accumulation of (18)F-FDG in the metastatic lymph nodes, which contain only a small number of cancer cells, was caused by the enhanced uptake of (18)F-FDG by activated T-lymphocytes due to host immunity against cancer cells present in metastatic lymph nodes.

Targeted biopsy based on ADC map in the detection and localization of prostate cancer: A feasibility study

To investigate the feasibility of targeted biopsy based on an apparent diffusion coefficient (ADC) map in the detection and localization of prostate cancer.