fluoro-D-glucose Uptake Research Articles

Animal PET for Thioacetamide-Induced Rat Cholangiocarcinoma: A Novel and Reliable Platform

Cholangiocarcinoma (CCA) is a lethal disease afflicting many thousands of patients worldwide. We have previously developed an oral thioacetamide (TAA)-induced model of rat CCA that recapitulates the histologic progression of human CCA. Our objective was to evaluate the feasibility of animal PET in detecting CCA in the setting of the TAA rat model. Male Sprague-Dawley rats (n = 30) were used in this study. Drinking water with TAA 300 mg/l was administered orally in 26 rats, and animal PET was performed at 20 weeks after initiation of TAA. A total of four rats served as controls. Animal PET images were acquired sequentially using both C-11 acetate and 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) to determine the optimal tracer. Dynamic animal PET images were collected to assess the optimal scan time based on the highest tumor-to-liver (T/L) ratio using time-activity curves. Animal PET findings were compared lesion by lesion with the results of autoradiography and the histological data. FDG animal PET images had a higher T/L ratio compared to images obtained with C-11 acetate as a marker. The optimal scan time for FDG animal PET was determined as 90 min postinjection of the tracer. This was when the T/L ratio reached its peak. Necropsy and histology confirmed the presence of TAA-induced CCA in 22 rats (84.6 %). Static animal PET images showed intense FDG uptake in 17 of the 22 tumor-bearing animals (77.3%). The average T/L ratio was 1.60 +/- 0.09. The sensitivity and specificity of animal PET in the detection of CCA were 77% (17/22) and 100% (4/4), respectively. We conclude that animal PET in the setting of the TAA rat model seems to be feasible for the detection of CCA. Future translational studies are needed to confirm and expand our findings.

Positron emission tomography as a tool for early prediction of therapy outcome in patients with soft tissue sarcoma

10572 Background: We used 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) to evaluate the FDG uptake in patients with soft tissue sarcoma (STS). Treatment effect was assessed with regard to prediction of therapy outcome. Methods: The evaluation includes 27 patients with high risk STS receiving chemotherapy consisting of doxorubicin 75 mg/m2/day 1 and ifosfamide 1,500 mg/m2/day 1–4 (AI-G regimen) or etoposide 125 mg/m2/day 1+4, ifosfamide 1,500 mg/m2/day 1–4 and doxorubicin 50 mg/m2/day 1 (EIA regimen). Patients were examined using PET prior to onset of therapy and after completion of the first cycle of AI-G and after two cycles of EIA chemotherapy, respectively. Restaging according to RECIST criteria using computed tomography and magnetic resonance tomography was performed after six cycles of AI-G or four cycles of EIA chemotherapy and served for reference. Results: Clinical outcome of 27 evaluable patients was as follows: two patients with no evidence of disease, seven with partial remission, 14 with stable disease, and four patients with progressive disease. Median average standard uptake value (SUV) prior to onset of chemotherapy was 3.5 [range: 0 - 27.9] in comparison to 2.4 [range: 0 - 9.9] after chemotherapy treatment. Median SUVmax was 11.5 [range: 0 - 44.7] prior to chemotherapy in comparison to 7.9 [range: 0 - 21.7] following therapy. A significant difference of the progression-free survival for patients with a decrease in SUV (responders) in comparison to patients with an increase or stable SUV (non-responders) could be demonstrated (p = 0.0187). Conclusions: On the basis of these data, PET can be used as an easily measurable tool for early prediction of chemosensitivity of the tumor and moreover of the therapy outcome. Moreover, PET may even complement the existing RECIST criteria for tumor response evaluation. No significant financial relationships to disclose.

Early Prediction of Therapy Outcome in Patients with High-Risk Soft Tissue Sarcoma Using Positron Emission Tomography

Background: We used 2-deoxy-2-[¹⁸F]fluoro-D-glucose (FDG) positron emission tomography (PET) to evaluate the FDG uptake in patients with soft tissue sarcoma (STS). Treatment effect was assessed with regard to prediction of therapy outcome. Patients and Methods: The ongoing evaluation includes 27 patients with high-risk STS receiving chemotherapy consisting of doxorubicin and ifosfamide (AI-G regimen), or etoposide, ifosfamide and doxorubicin (EIA regimen). Patients were examined using PET prior to onset of therapy, and after completion of the first cycle of AI-G and after 2 cycles of EIA chemotherapy, respectively. Restaging according to RECIST was performed after 6 cycles of AI-G or 4 cycles of EIA chemotherapy and served as reference. Results: Clinical outcome of 27 evaluable patients was as follows: 2 patients with no evidence of disease, 7 with partial remission, 14 with stable disease, and 4 patients with progressive disease. A significant difference of the progression-free survival for patients with a decrease in the standardised uptake value (SUV; responders) in comparison to patients with an increase or stable SUV (non-responders) could be demonstrated (p = 0.0187). Conclusion: On the basis of these data, prediction of chemo-sensitivity of the tumour and moreover of the therapy outcome might be possible.

MicroCT Liver Contrast Agent Enhancement Over Time, Dose, and Mouse Strain

The aim of this study was to examine strain differences in the uptake of Fenestra liver contrast agent (LC) in Nude, C57, and severe-combined immunodeficient (SCID) mice. In addition, we aimed to determine optimum dosing and to determine if there are positron emission tomography (PET)-attenuation effects on 2-deoxy-2[F-18]fluoro-D-glucose (FDG) values due to Fenestra LC. Nude, C57, and SCID mice were injected via tail vein at 5.0, 7.5, 10.0, and 15.0 ml/kg with contrast agent and imaged using micro computed tomography (microCT) 2 h after uptake and then daily up to 7 days. Mice were imaged by microPET/CT with FDG, with or without contrast agent. Significant variations in contrast were observed between mouse strains. SCID mice had significantly more spleen uptake of contrast than the other strains, and C57 mice had significantly more liver uptake of contrast than other strains. Across all strains, the spleen showed significantly higher uptake and duration of contrast than liver. Only the heart showed a significant attenuation of FDG uptake following contrast administration. Strain-specific variations in Fenestra LC uptake and signal duration were observed. At 7.5 ml/kg, this contrast agent is effective for imaging for 1 day, whereas at 15 ml/kg, it can be used up to 1 week. Fenestra LC does not appear to attenuate FDG uptake at 15 ml/kg for most tissues; therefore, it can be used in conjunction with microPET imaging studies.

FDG-PET/CT in the Evaluation of Cutaneous T-Cell Lymphoma

This comprehensive case series illustrates the findings on 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) positron-emission tomography/computed tomography (PET/CT) of patients with varying stages of cutaneous T-cell lymphoma (CTCL). Patients were imaged with full-body scanning using a General Electric Discovery ST 16-slice PET/CT machine. Patients were assessed by PET/CT for cutaneous, nodal, and solid organ FDG uptake, indicative of highly metabolically active (i.e., putatively malignant cells) disease, and comparisons were made to CT data alone and to the physical examination. Several key observations strongly suggested that information afforded by PET/CT scan may be valuable. Various cutaneous lesions, from thin subtle plaques to thick tumors, were revealed and corresponded accurately to the cutaneous examination. In the case of subcutaneous lesions, PET/CT outperformed physical exam. CT also provided the depth/thickness of lesions. The differing levels of FDG uptake in enlarged nodes found within an individual patient as well as among different patients may potentially distinguish reactive from malignant adenopathy. Additionally, lymph nodes that did not meet staging size criteria (e.g., were not > 1 cm) revealed increased metabolic activity and, therefore, could be targeted for subsequent monitoring or biopsy. In addition, PET/CT identified visceral involvement in cases with advanced disease. In summary, PET/CT can provide physiologic and anatomic information on the wide diversity of external and internal lesions in CTCL and, therefore, may have great potential for improving the staging and monitoring of response to therapy of cutaneous, nodal, and visceral disease.

Scalene muscle uptake: a potential pitfall in head and neck PET/CT

To describe increased 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG) uptake in the scalene muscles in a large population of patients referred for evaluation with FDG positron emission tomography/computed tomography (PET/CT) imaging. The study met criteria for institutional review board exemption. FDG PET/CT images from 410 patients (179 males; mean age 56.8 years, range 6-88) were retrospectively reviewed for the presence or absence of FDG uptake in the neck that corresponded to the scalene muscles on the concurrent CT scan. Medical records were reviewed and data including age, sex, smoking history, reason for referral, and history of obstructive airways disease, thoracotomy, and thoracic radiation were recorded and evaluated. One hundred and forty-seven of the 410 scans (36%) demonstrated increased FDG uptake on PET that corresponded to the scalene muscles on the CT scan. The uptake was most often bilateral, symmetrical, and linear (n = 117). Other patterns of scalene muscle uptake included unilateral and linear uptake (n = 27) and unilateral and focal uptake (n = 3). Scalene muscle uptake was more common in patients referred for evaluation of lung carcinomas compared to other types of tumors (52% vs. 32%, p = 0.05). Linear FDG uptake in scalene muscles is a commonly seen pattern on PET/CT. This finding should be recognized as a distinct entity and not misinterpreted on transverse images as metastatic disease.

2-Deoxy-2-[F-18]fluoro-D-glucose Joint Uptake on Positron Emission Tomography Images: Rheumatoid Arthritis Versus Osteoarthritis

PurposePrevious positron emission tomography (PET) studies have shown increased 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake in joints of patients with osteoarthritis (OA) and inflamed joints of patients with rheumatoid arthritis (RA). This study compares FDG uptake in joints of RA and OA patients and FDG-uptake with clinical signs of inflammation.ProceduresFDG-PET scans of hands and wrists were performed in patients with RA and primary OA. PET data were compared with clinical data.Results29% of RA joints and 6% of OA joints showed elevated FDG-uptake. The level of uptake in PET-positive OA joints was not significantly different from that in RA joints. The majority of PET results of RA joints corresponded with clinical findings. Clinical synovitis was found some OA joints with FDG-uptake.ConclusionsFDG-uptake was observed in the majority of clinically inflamed RA joints and in a few OA joints with no significant difference in uptake level. The latter may be due to secondary synovitis.

Etiopathologies Associated with Intercostal Muscle Hypermetabolism and Prominent Right Ventricle Visualization on 2-Deoxy-2[F-18]fluoro-d-glucose-Positron Emission Tomography: Significance of an Incidental Finding and in the Setting of a Known Pulmonary Disease

The present study was undertaken to investigate the significance of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake in the intercostal muscles (ICM) and prominent visualization of right ventricle (RV) in FDG-positron emission tomography (PET) scans and its implications. Patients identified to have FDG uptake in the ICM with or without prominent visualization of the RV either incidentally or in the background of an existing explanatory cause at the time of FDG-PET studies were included in this retrospective study. These patients had undergone FDG-PET either for ruling out malignancy or for disease monitoring purposes in setting a proven malignancy. We reviewed the clinical and investigational records (including computed tomography [CT] thorax, chest X-ray, 2-D echo and pulmonary function tests, and arterial blood gas analysis) of the group with incidental FDG uptake for revelation of a pathology explaining such uptake. A total of 14 cases with 16 FDG-PET studies were identified from the retrospective examination of case records. One patient had three FDG-PET at different time points of his disease course. The patient population included 13 males and one female with age range 46-88 years. The patients were classified into two groups: (1) cases with isolated ICM uptake (n=10); (2) cases with both ICM and RV uptake (n=4). Among 10 patients with isolated ICM uptake, in six patients it was a serendipitous observation, whereas four patients had existing explanatory cause at the time of FDG-PET. The causes found to be associated included COPD, asthma, recent heart failure, interstitial lung disease (post external radiotherapy) and pulmonary embolism, atelectasis with pleural effusion. In all four cases with associated RV uptake, there was evidence of pulmonary hypertension (PH). Among these, in one patient this was a serendipitous observation. He had evidence of interstitial lung disease (ILD) in CT thorax, and 2-D echo showed moderate PH. The remaining three patients had cor pulmonale secondary to COPD, pneumoconiosis, and Swyer James Syndrome with associated severe PH. The SUVmax ratio of the RV-to-LV free wall ranged from 0.53 to 1.04 in the cases with prominent RV uptake. One patient had multiple FDG-PET studies and have shown reduction of RV uptake in the last scan consistent with the clinical impression of improvement of cor pulmonale. Both intercostal muscle and prominent RV uptake in FDG-PET can be associated with a spectrum of causes (including both obstructive and restrictive airway diseases) that lead to breathing exertion. These are important markers, which could signify underlying pulmonary disease and pulmonary hypertension, respectively. Associated prominent RV uptake strongly indicates presence of pulmonary hypertension and the uptake in the right heart can subserve a valuable surrogate marker in the treatment-monitoring scenario of a known PH.

A Small Animal Positron Emission Tomography Study of the Effect of Chemotherapy and Hormonal Therapy on the Uptake of 2-Deoxy-2-[F-18]fluoro-d-glucose in Murine Models of Breast Cancer

We used small animal positron emission tomography (PET) imaging to monitor the time-course of tumor metabolic response to hormone and chemotherapy in a murine model of hormone-sensitive breast cancer. Estrogen receptor positive murine mammary carcinomas were inoculated in Balb/c mice. Small animal PET imaging using 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) was used to assess tumor metabolic activity. Imaging was done before and at days 1, 7, and 14 after the administration of doxorubicin, methotrexate, letrozole, or placebo. The tumor uptake of FDG was calculated from a region-of-interest drawn around the tumor. All treatments resulted in a decrease in tumor growth rate and end volume compared to untreated control. FDG uptake was also markedly decreased after treatment although a flare reaction was observed on PET at day 7, the intensity of which varied according to the treatment modality. PET imaging is sensitive to detect early changes associated with therapy in murine breast cancer models. A flare reaction was observed 7 days after the initiation of therapy.

Quantitative Evaluation of 2-Deoxy-2[F-18]fluoro-d-glucose-Positron Emission Tomography Imaging on the Woodchuck Model of Hepatocellular Carcinoma with Histological Correlation

The Eastern woodchuck (Marmota monax) is considered as a naturally occurring animal model of hepatocellular carcinoma (HCC). The performance of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) for imaging HCC on the woodchuck using Positron emission tomography (PET) was investigated in this study. Dynamic FDG-PET scans were performed on five woodchucks with HCC and one healthy woodchuck before removal and processing of the liver tissues for histology. The parameters of a two-tissue compartment model with dual input were estimated using weighted least squares (WLS). Ten HCCs were confirmed histologically. Six HCCs had a tumor-to-liver standardized uptake value (SUV) ratio < or =1.15, a k (4) / k (3) ratio similar to that in hepatic tissues and were well-differentiated. Four HCCs had a tumor-to-liver SUV ratio >1.15, a lower k (4) / k (3) ratio than the hepatic tissues and were moderately differentiated. Increased FDG uptake was observed in HCCs that were the least differentiated and correlated with a lower k (4) / k (3) ratio.

Standardized Uptake Value Atlas: Characterization of Physiological 2-Deoxy-2-[18F]fluoro-d-glucose Uptake in Normal Tissues

The purpose of this study was to map the distribution of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake in organs of patients with no known abnormalities in those tissues. We measured maximum and mean standardized uptake values (SUV) from FDG-positron emission tomography (PET)/computed tomography (CT) obtained from 98 patients (48 males and 50 females). Significant uptake (mean SUVmean>2.5) was visualized in the cerebellum (8.0+/-2.2), soft palate (2.92+/-0.86), palatine tonsils (3.45+/-1.4), lingual tonsils (3.08+/-1.05), sublingual glands (3.3+/-1.5), and testes (2.57+/-0.56). Negative correlation for FDG uptake versus age was observed for the palatine tonsils, sublingual glands, and lungs (P<0.001). Better understanding of physiological uptake throughout the body is valuable for improved interpretive accuracy and should be useful for future semi-automated comparisons to a normal SUV database.

Evaluation of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in gastric carcinoma: relation to histological subtypes, depth of tumor invasion, and glucose transporter-1 expression

Variable uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been noticed in positron emission tomography (PET) studies of gastric carcinoma patients, with low uptake occurring especially in some particular histological subtypes and early carcinomas. But this phenomenon has not been adequately explained. The aim of the present study is to clarify FDG uptake in gastric carcinomas especially focusing on histological subtypes, the depth of tumor invasion, and glucose transporter-1 (GLUT-1) expression which is considered to be one of the major factors for higher FDG uptake in human malignant tumors. FDG-PET was performed on 35 preoperative patients with gastric carcinoma. Forty macroscopically distinguishable lesions on a surgical specimen were histologically classified into two subtypes: Cohesive type (papillary adenocarcinoma, tubular adenocarcinoma, and solid type poorly differentiated adenocarcinoma) or Noncohesive type (signet-ring cell carcinoma and non-solid type poorly differentiated carcinoma). GLUT-1 expression was immunohistochemically determined. Histological parameters (GLUT-1 expression, histological subtypes, the depth of invasion, lymphatic permeation, venous invasion and tumor size) were evaluated, and factors for FDG uptake (detectability and the degree) and GLUT-1 overexpression were determined by multiple regression analysis. Nineteen of 40 gastric carcinomas showed detectable FDG uptake (48%), multiple regression analysis revealed that both the depth of invasion and histological subtypes are independent factors that influence the detectable FDG uptake in gastric carcinoma (R2 = 0.66). GLUT-1 expression was seen from an early cancer stage and the cohesive type was an independent factor influencing the overexpression of GLUT-1 (R2 = 0.66). GLUT-1 expression was the most influential factor for the degree of FDG uptake in gastric carcinoma (R2 = 0.68). This study provided important information on the clinical application of FDG-PET in gastric carcinoma that early or non-cohesive gastric carcinoma may show lower FDG uptake. Therefore, the usefulness of FDG-PET for the detection of gastric carcinoma is limited. But there is a possibility that FDG uptake associated with GLUT-1 expression may serve as a prognostic factor of gastric carcinoma representing tumor metabolism.

Tumor fluoro-2-deoxy- d-glucose avidity on positron emission tomographic scan predicts mortality in patients with early-stage pure and mixed bronchioloalveolar carcinoma

Bronchioloalveolar carcinoma is a clinically heterogeneous subtype of non-small cell lung carcinoma that frequently has low 2-[18F]fluoro-D-glucose (FDG) uptake on positron emission tomographic scanning. We investigated whether tumor FDG avidity was associated with worse survival among patients with completely resected node-negative pure and mixed bronchioloalveolar carcinoma. We performed a cohort study of 36 patients who had completely resected pure and mixed bronchioloalveolar carcinoma between 1998 and 2004, who had no hilar or mediastinal lymph node metastases, and who had undergone a preoperative positron emission tomographic scan. Tumor FDG avidity was defined as a standardized uptake value of 2.5 or greater. Survival analysis was performed with a proportional hazards model. Of 36 patients studied, 26 patients (72%) were alive and 10 patients (28%) were dead after a median follow-up of 31 months (interquartile range 17-41 months). Seventeen patients (47%) had FDG-avid tumors, and 19 patients (53%) had non-avid tumors. Three-year survival was 49% in the FDG-avid group and 95% in the non-avid group (P = .005). FDG avidity had a hazard ratio of death of 8.6 (95% confidence interval 1.4-244.7, P = .02) after adjusting for tumor size, the presence of multifocal bronchioloalveolar carcinoma, and the presence of histologically mixed bronchioloalveolar carcinoma. Preoperative tumor FDG standardized uptake value of 2.5 or greater on positron emission tomography is a powerful predictor of long-term mortality in patients with lymph node-negative pure and mixed bronchioloalveolar carcinoma who undergo complete surgical resection. Patients with a high level of FDG uptake (standardized uptake value > or = 2.5) may benefit from adjuvant chemotherapy or more frequent clinical follow-up.

Optimization of Whole-Body Positron Emission Tomography Imaging by Using Delayed 2-Deoxy-2-[F-18]fluoro-d-glucose Injection Following I.V. Insulin in Diabetic Patients

High blood glucose levels may decrease the sensitivity of 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG)-positron emission tomography (PET). The goal of this study was to assess whether intravenous (i.v.) insulin followed by FDG injection 60 minutes later could decrease the blood glucose level of hyperglycemic patients without altering muscular, liver, or lung FDG uptake. We evaluated 53 diabetic patients with a fasting glycemia higher than 7.0 mmol/l. The control group consisted of 53 nondiabetic patients with a normal fasting glycemia. Sixty minutes before FDG injection, all diabetic patients received up to two intravenous bolus of insulin. Regions of interest were drawn over the lungs, heart, liver, skeletal muscles, and over the most active lung nodule, if present, to calculate a standardized uptake value (SUV) normalized to the lean body weight. After one or two boluses of insulin (mean 3.4 units), 39 diabetic patients decreased their blood glucose level from 9.4 +/- 1.8 to 6.1 +/- 1.3 mmol/l. In 14 patients, two doses of insulin (mean 4.5 +/- 2.3 units) were not sufficient, but managed to decrease the blood glucose level from 10.6 +/- 2.1 to 9.1 +/- 2.1 mmol/l. There was no significant difference for the SUV calculated on the lung, liver, heart, and skeletal muscles. No differences were noted in lung tumor uptake in patients who received insulin compared to the control group. With a sufficient waiting period between the insulin and FDG injections, an i.v. bolus of insulin makes it possible to effectively decrease glycemia of diabetic patients without increasing muscular FDG uptake.

Standardized Uptake Values of Normal Breast Tissue with 2-Deoxy-2-[F-18]Fluoro-d-glucose Positron Emission Tomography: Variations with Age, Breast Density, and Menopausal Status

This study was conducted to assess the effect of breast density, age, and menopausal status on the 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) uptake in normal breast tissue by quantitative standardized uptake values (SUV). A total of 96 patients (premenopausal 54; postmenopausal 42) with histologically proven unilateral breast cancer who underwent FDG-positron emission tomography (PET) scans for staging were included in this study. The median age was 52+/-11 years (range 32-79 years). Fifty-nine patients had grade III or IV mammographic density (dense breast), whereas 37 patients had grade I or II breast density (nondense) according to the ACR Lexicon criteria. In the present study, we analyzed maximum and average SUVs for contralateral normal breast. Maximum and average SUVs for normal dense breasts were 1.02+/-0.30 and 0.84+/-0.27, respectively. Similar values for the nondense breasts were 0.66+/-0.24 and 0.53+/-0.23, respectively. Both maximum and average SUVs of dense breasts were significantly higher than those of nondense breasts (p<0.001). There was no significant difference in SUVs of nipple in patients with dense and nondense breasts. There was no significant effect of age and menopausal status on SUVs of normal breast. However, there were trends of negative relationship, i.e., decreasing SUVs with increasing age. There was a significant difference in SUVs between the dense and nondense normal breast. However, the maximum SUVs in the dense breasts were well below the threshold of 2.5, a widely used cutoff value for malignancy. Menopausal status and age do not significantly affect the uptake of FDG.

Longitudinally Quantitative 2-Deoxy-2-[18F]fluoro-d-glucose Micro Positron Emission Tomography Imaging for Efficacy of New Anticancer Drugs: A Case Study with Bortezomib in Prostate Cancer Murine Model

The aim of this study was to validate quantitative metabolic response of tumors to a treatment measured by longitudinal 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) micro positron emission tomography (microPET) as a robust tool for preclinical evaluation of new anticancer agents. Severe combined immunodeficiency mice with CWR22 xenografts were intravenously treated with bortezomib (Velcade) at 0.8 mg/kg on days 0, 3, 7, 10, and 14 and imaged with FDG microPET before, during and after treatment. Quantitative indices of tumor FDG uptake were developed. FDG microPET images successfully revealed the gradual reduction of tumor FDG uptake on day 4 onward despite no absolute tumor shrinkage. The standardized uptake values of FDG in tumors was reduced to 43% of the baseline values. Using the total tumor FDG uptake as the viable tumor burden, we found 86% tumor inhibition, compared to a 55% tumor growth inhibition in tumor volume measurement. FDG microPET imaging can provide an additional dimension of the efficacy of anticancer therapies that may otherwise be underestimated by tumor volume measurement.

The benefits of a restaging PET scan after two cycles of neoadjuvant chemotherapy for resectable non-small cell lung cancer

17092 Background: Neoadjuvant chemotherapy can potentially improve the outlook of resectable non-small cell lung cancer (NSCLC). Whole-body 2-deoxy-2-[18F] fluoro-D-glucose (FDG)-PET is often used as an initial test to determine tumor resectability, but its role as a restaging test after neoadjuvant chemotherapy is unclear. Restaging PET after neoadjuvant chemoradiation helps identify unexpected distant metastasis and avoid unnecessary thoracotomy. We explored its benefits after neoadjuvant chemotherapy. Methods: Patients with stage IB-IIIA and selected IIIB resectable NSCLC received induction gemcitabine (1,000 mg/m2) and vinorelbine (25 mg/m2) on days 1, 8, 22, and 29. PET and CT scan were performed before enrollment and between day 43–50. Response from CT scan was defined by RECIST criteria; from PET, defined as &gt;20% reduction in the SUVmax (a decrease of &gt; 2 SD of spontaneous change in FDG uptake, previously validated). This abstract explores patients participated in a published prospective trial with available both pre- and post-treatment PET scans. Results: There were 19 patients: stage IB-7, stage IIB-2, and stage III-10. Median age was 67 years. Mean interval between staging and restaging PET scan was 59 days. By PET, 10 patients responded. By RECIST criteria, complete response occurred in 0, partial response in 6, and stable disease in 13 patients. Most successfully underwent a complete resection, but positive margins were present in 3; multi-station lymph node involvement was found intraoperatively in 1 patient. Overall median survival was 20.5 months. We found that restaging PET did not help identify any distant metastasis. Moreover, no survival difference was observed between PET responders and non-responders, though PET responders had more advanced stage than their counterparts: median survival 16 months vs. not reached (p = 0.08 adjusted for stage). PET response was correlated with RECIST response (p = 0.05) as well as the response as obtained by SUV max divided by the activity of contralateral lung or aorta ratio. Conclusion: Based on this small group of patients, a restaging PET scan obtained after two cycles of neoadjuvant chemotherapy among patients with resectable NSCLC did not appear to impact the decision on a planned thoracotomy. No significant financial relationships to disclose.

Merkel Cell Carcinoma: Is there a Role for 2-Deoxy-2-[F-18]fluoro-d-glucose-Positron Emission Tomography/Computed Tomography?

2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is becoming widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single study. The role of FDG-PET/CT is proven in lymphoma, melanoma, colorectal carcinoma, and other cancers. However, there are rare malignancies such as Merkel cell carcinoma that can potentially be evaluated with PET/CT. We were therefore prompted to review our experience with FDG-PET/CT in the management of patients with Merkel cell carcinoma. This is a retrospective case series of six patients with Merkel cell carcinoma, 58-81 years old (average 69 +/- 8.3), who had whole-body PET/CT at our institution from January 1st, 2003 to August 31st, 2005. Two patients were women and four were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. Twelve examinations were acquired for the six patients (one patient had six PET/CT, one patient had two PET/CT, and four patients had one PET/CT). The injected FDG doses ranged 381.1-669.7 MBq (average 573.5 +/- 70.3). Four patients had the PET/CT as part of initial staging, and two patients had the exam for restaging (after surgery and XRT). A total of six Merkel lesions (pancreas, adrenal, lip, submandibular lymph nodes, cervical lymph nodes, and parapharyngeal soft tissue) were identified in three patients and confirmed on histopathological examination. The FDG uptake in these areas was intense, with maximum standardized uptake value (SUVmax) values of 5-14 (average 10.4 +/- 3.8). In one patient, the PET/CT scan identified abnormal focal distal sigmoid uptake that was biopsied and diagnosed as adenocarcinoma. Two patients had negative scans and had no clinical evidence of disease on follow-up office visits (up to one year after PET/CT). This case series suggests that FDG-PET/CT may have a promising role in the management of patients with Merkel cell carcinoma.

Use of Positron Emission Tomography to Target Prostate Cancer Gene Therapy by Oncolytic Herpes Simplex Virus

Herpes simplex virus (HSV) oncolytic gene therapy is a promising treatment modality against cancer. We have demonstrated that androgen-induced cellular changes enhance oncolytic viral replication and improve efficacy in the treatment of androgen-dependent prostate cancer cell line. Imaging of changes in 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake by positron emission tomography (PET) is a sensitive method of detecting altered cellular metabolism involved in cancer therapy. We therefore hypothesized that FDG-PET can predict tumor response to oncolytic HSV therapy. In this study, androgen increased cell kill (74%) in vitro and enhanced viral yield (2.4-fold) in vivo following HSV therapy. This enhanced efficacy was predicted by high FDG accumulation in intact animals compared to low FDG uptake following orchiectomy (p = 0.002). This proof-of-concept study provides the mechanistic basis for selecting patients for targeted oncolytic viral therapy by means of a noninvasive molecular imaging method in the treatment of prostate cancer.

Usefulness of 3′-[F-18]Fluoro-3′-deoxythymidine with Positron Emission Tomography in Predicting Breast Cancer Response to Therapy

The usefulness of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) in monitoring breast cancer response to chemotherapy has previously been reported. Elevated uptake of FDG by treated tumors can persist however, particularly in the early period after treatment is initiated. 3'-[F-18]Fluoro-3'-deoxythymidine (FLT) has been developed as a marker for cellular proliferation and, in principle, could be a more accurate predictor of the long-term effect of chemotherapy on tumor viability. We examined side-by-side FDG and FLT imaging for monitoring and predicting tumor response to chemotherapy. Fourteen patients with newly diagnosed primary or metastatic breast cancer, who were about to commence a new pharmacologic treatment regimen, were prospectively studied. Dynamic 3-D PET imaging of uptake into a field of view centered over tumor began immediately after administration of FDG or FLT (150 MBq). After 45 minutes of dynamic acquisition, a clinically standard whole-body PET scan was acquired. Patients were scanned with both tracers on two separate days within one week of each other (1) before beginning treatment, (2) two weeks following the end of the first cycle of the new regimen, and (3) following the final cycle of that regimen, or one year after the initial PET scans, whichever came first. (Median and mean times of early scans were 5.0 and 6.6 weeks after treatment initiation; median and mean times for late scans were 26.0 and 30.6 weeks after treatment initiation.) Scan data were analyzed on both tumor-by-tumor and patient-by-patient bases, and compared to each patient's clinical course. Mean change in FLT uptake in primary and metastatic tumors after the first course of chemotherapy showed a significant correlation with late (av. interval 5.8 months) changes in CA27.29 tumor marker levels (r = 0.79, P = 0.001). When comparing changes in tracer uptake after one chemotherapy course versus late changes in tumor size as measured by CT scans, FLT was again a good predictor of eventual tumor response (r = 0.74, P = 0.01). Tumor uptake of FLT was near-maximal by 10 minutes after injection. The time frame five to 10 minutes postinjection of FLT produced standardized uptake value (SUV) values highly correlated with SUV values obtained after 45-minute uptake (r = 0.83, P < 0.0001), and changes in these early SUVs after the first course of chemotherapy correlated with late changes in CA27.29 (r = 0.93, P = 0.003). A 10-minute FLT-PET scan acquired two weeks after the end of the first course of chemotherapy is useful for predicting longer-term efficacy of chemotherapy regimens for women with breast cancer.