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Biomedical subjects

M Donald Blaufox

Publications and source records attributed to M Donald Blaufox.

12 recordsLinked to original sources

Nuclear medicine studies of the prostate, testes, and bladder.

During the last decade, there has been a significant advancement in imaging of urologic diseases. Transrectal ultrasound (TRUS), computerized tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET) are still experiencing new developments in urology. Despite these many technological advances, the initial diagnostic procedure for a patient with suspected prostate cancer (PC) is multiple site blind prostate biopsies. There is a need for a noninvasive metabolic imaging modality to direct the site of biopsy to decrease the sampling error. MRS seems promising but as it is a costly and more time-consuming test, further studies are needed to evaluate its clinical utility. Currently, PET does not play any role to direct biopsy. Acetate and choline appear to be better tracers than FDG for the detection of a prostate lesion, however, further well-organized studies are needed before any of these agents can be used clinically. Incidental detection of intense focal uptake in the prostate during whole body PET scanning should be evaluated with prostate-specific antigen (PSA) and TRUS-guided biopsy. Although FDG is inferior to other tracers for primary staging, it may be useful in selected patients with suspected high-grade cancer. The role of ProstaScint scan is still controversial for detection of recurrent PC. This study may be helpful for evaluating nodal metastases when PSA is elevated and bone scan is negative. Bone scan remains the study of choice when bone metastases are suspected (PSA>15-20 ng/mL+/-bone pain). Acetate and choline provide better accuracy than FDG in the detection of local soft tissue disease, nodal involvement, and distant metastases. High FDG uptake may be indicative of more aggressive and possibly androgen-independent disease. PET/CT with any of the above PET tracers will most likely be preferred to the PET scan alone due to better localization of a hot lesion in PET/CT. Nuclear medicine studies also have been used to evaluate acute scrotum and testicular neoplasms. Scrotal scintigraphy has lost its popularity to Doppler ultrasound in the evaluation of the acute scrotum. In testicular tumors, FDG-PET appears to be superior to conventional imaging modalities in initial staging, detection of residual/recurrence, and monitoring treatment response. Tumor markers after treatment occasionally are elevated and cannot locate the site of recurrence, FDG-PET can play a very important role in this regard. Nuclear medicine studies also have been used to evaluate diseases of the urinary bladder. Radionuclide cystography is more sensitive and has less than 1/20 the radiation exposure of the conventional contrast enhanced micturating cystourethrogram (MCU). However, the utility of FDG-PET in the evaluation of bladder cancer seems to be limited to the evaluation of distant metastases. 11C-Methionine and choline may be a better option for local and nodal disease due to their negligible excretion in the urine.

Humans↗

FDG-PET and CT characterization of adrenal lesions in cancer patients.

PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) may differentiate benign from malignant adrenal lesions. In this study, standardized uptake values (SUVs), visual interpretation, and computed tomography (CT) data were correlated with the final diagnosis to determine the contribution of adrenal FDG-PET in patients with known non-adrenal cancer. METHODS: Ninety-two patients with adrenal lesions on CT underwent FDG-PET. Eighty adrenals in 74 patients met the inclusion criteria (PET scan within 4 weeks of CT plus >1 year of follow-up after PET scan with repeat CT or biopsy for final diagnosis). CT was considered positive for metastases (CT+) based on two of the following three criteria: >4 cm, Hounsfield units (HU) >30, and delayed contrast enhancement. Lesions with <2 cm, with HU <20, and showing no enhancement were considered benign (CT-). Remaining lesions were considered indeterminate (CT-Ind). Visually, adrenal uptake exceeding liver uptake was considered PET positive (PET+). Diagnosis of metastases was based on biopsy or interval CT growth (unchanged >1 year=benign). SUV(max) and SUV(avg) were calculated from a 4 x 4 pixel region of interest drawn from CT, PET, and fused images. A receiver operator curve (ROC) determined the SUV with the best sensitivity and specificity. RESULTS: Overall, PET was 93% sensitive and 96% specific for metastases. A SUV(max) of 3.4 was 95% sensitive and 86% specific. A SUV(avg) of 3.1 was 95% sensitive and 90% specific. There was no significant difference between visual interpretation and SUV (SUV(max) or SUV(avg)). Among CT+ and CT- lesions, PET was 100% sensitive and 96% specific; CT was 86% sensitive and 100% specific. In the CT-Ind group, PET was 88% sensitive and 96% specific. CONCLUSION: PET accurately characterized adrenal lesions. Visual interpretation was as accurate as SUV. FDG-PET was most useful in the 52.5% of cancer patients with inconclusive adrenal lesions on CT.

Adrenal Gland Neoplasms↗

A metaanalysis of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography in the staging and restaging of patients with lymphoma.

BACKGROUND: In recent years, the use of positron emission tomography (PET) has become widespread for the staging and follow-up of several malignancies. In the current study, the authors conducted a metaanalysis of the published literature to evaluate the diagnostic performance of 18F-2-deoxy-2-fluoro-D-glucose PET (FDG-PET) in the staging of patients with lymphoma. METHODS: The authors conducted a systematic MEDLINE search of articles published between January 1995 and June 2004. Studies that evaluated FDG-PET with a dedicated camera and that reported sufficient data to permit the calculation of sensitivity and specificity were included in the analysis. Two reviewers independently reviewed the eligibility of the studies and abstracted data (sample population; characteristics of FDG-PET; and the number of true-positive results, true-negative results, false-positive results, and false-negative results). The authors estimated the pooled sensitivity, false-positive rate, and maximum joint sensitivity and specificity. RESULTS: Twenty studies were eligible for the metaanalysis. Fourteen studies included patient-based data, comprising a sample size of 854 subjects, and 7 studies included lesion-based data, totaling 3658 lesions. Among those studies with patient-based data, the median sensitivity was 90.3% and the median specificity was 91.1%. The pooled sensitivity was 90.9% (95% confidence interval [95% CI], 88.0-93.4) and the pooled false-positive rate was 10.3% (95% CI, 7.4-13.8). The maximum joint sensitivity and specificity was 87.8% (95% CI, 85.0-90.7). The pooled sensitivity and false-positive rate appeared to be higher in patients with Hodgkin disease compared with those with non-Hodgkin lymphoma. CONCLUSIONS: The results of the current study indicate that FDG-PET is a valuable tool for the staging and restaging of patients with lymphoma; showing a high positivity and specifity. Clinicians may consider adding FDG-PET to the staging workup of patients with lymphoma.

Fluorodeoxyglucose F18↗

Positherapy: targeted nuclear therapy of breast cancer with 18F-2-deoxy-2-fluoro-D-glucose.

Breast cancer remains a major cause of cancer death in women in the United States. Novel therapies are needed for patients when standard treatments are ineffective. We have recently shown on a cellular level the therapeutic potential of positrons in malignancy. Here, we report for the first time positron therapy with (18)F-2-deoxy-2-fluoro-D-glucose ((18)F-FDG) in a breast cancer animal model to affect tumor growth rate and survival (positherapy). We used xenografted mammary tumors in nude mice using Notch mammary cancer cells which also express ras oncogene. Notch xenografted tumors actively took up (18)F-FDG with a tumor to normal tissue ratio of 3.24. Tumor-bearing mice were treated with 2.5 mCi (18)F-FDG, which is equivalent to the physiological human maximum tolerated dose. Positherapy resulted in both significant prolongation of survival and decrease in tumor growth rate in comparison with nontreated controls. Immunoblot of Notch tumors showed the presence of glucose transporters (GLUT) 1, 4, and 8. Substantial differences between GLUT1, GLUT4, and GLUT8 were observed in their distribution within the tumor mass. Whereas GLUT4 and GLUT8 were distributed relatively homogeneously throughout the tumor, GLUT1 was confined to necrotic areas. Immunofluorescence double labeling was used to determine cellular localization of GLUTs. GLUT1 was expressed mostly at the cell membrane. GLUT4 and GLUT8 were mostly localized to cytoplasmic compartments with some GLUT4 expressed at or near the cell membrane in close proximity to GLUT1. Thus, GLUT1 was likely responsible for the (18)F-FDG uptake by tumor cells with some possible contribution from GLUT4. These results are important for the development of positherapy with (18)F-FDG for refractory metastatic breast and other cancers.

Animals↗

A meta-analysis of FDG-PET for the evaluation of breast cancer recurrence and metastases.

OBJECTIVE: To evaluate the diagnostic performance of 18F-2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) in the evaluation of breast cancer recurrence and metastases. DATA SOURCES: Articles published in medical journals during January 1995-June 2004 were identified by a systematic Medline search, supplemented by a manual search of the references listed in original and review articles. STUDY SELECTION: Studies that evaluated FDG-PET with a dedicated camera for the diagnosis of breast cancer recurrence or metastases, and reporting sufficient data to permit calculation of sensitivity and specificity, were included in the analysis. DATA EXTRACTION: Two reviewers independently reviewed the eligibility and abstracted data regarding the sample population, technical imaging characteristics of FDG-PET, and the number of true positives, true negatives, false positives and false negatives. Differences between readers were resolved by consensus. DATA SYNTHESIS: We used meta-analytic methods to estimate the pooled sensitivity, false positive rate, and the maximum joint sensitivity and specificity. Eighteen studies met the inclusion criteria. Sixteen studies included patient-based data, comprising a sample size of 808 subjects, and eight studies included lesion-based data, totaling 1013 lesions. Among the studies with patient-based data, the median sensitivity was 92.7%, and the median specificity was 81.6%. The pooled sensitivity was 90% [95% confidence interval (86.8-93.2)], and the pooled false positive rate was 11% [95% confidence interval (7.8-14.6)], after the exclusion of outliers. The maximum joint sensitivity and specificity, was 88% [95% confidence interval (86.0-90.6)]. CONCLUSION: These results indicate that FDG-PET is a valuable tool for detecting breast cancer recurrence and metastases.

Breast Neoplasms↗

Intra-individual variability of cardiac uptake on serial whole-body 18F-FDG PET.

OBJECTIVE: To measure the variability of cardiac uptake on serial whole-body F-FDG PET scans. METHODS: Two hundred and eighteen whole-body PET scans were performed in 47 patients with different primary malignancies between October 1996 and April 2003 on a dedicated PET system. The number of scans per patient ranged between four and nine. Two experienced nuclear medicine physicians reviewed the scans retrospectively using the non-attenuation corrected images to assess the cardiac FDG uptake. Patients with cardiac uptake less or equal to lung uptake were assigned in the "low" uptake group, and those with cardiac uptake more than the lung uptake were assigned to the "high" uptake group. The reproducibility of cardiac uptake on serial whole-body PET scans and the effect of age, sex, weight, diabetes and primary diagnosis on cardiac uptake was evaluated. RESULTS: There was very good reproducibility (intra-class correlation coefficient=0.77) of individual cardiac FDG uptake on serial whole-body PET scans. Diabetics (n=6) in comparison to non-diabetics were less likely to have high cardiac uptake (odds ratio (OR)=0.24, P<0.05). Patients with lymphoma (n=12) in comparison to patients with other primary diagnoses were more likely to have high cardiac uptake (OR=8.6, P<0.05). There was no association between cardiac uptake and age, sex or weight. CONCLUSION: Cardiac FDG uptake on whole-body PET does not appear to change significantly over time. It is likely that uptake is determined by individual characteristics; these likely include diabetes and primary diagnosis of lymphoma.

Adult↗

Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer.

BACKGROUND: Novel approaches are needed for breast cancer patients in whom standard therapy is not effective. 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was evaluated as a potential radiomolecular therapy agent in breast cancer animal models and, retrospectively, in patients with metastatic breast cancer. METHODS: Polyoma middle T antigen (PyMT) and mouse mammary tumor virus-NeuT transgenic mice with tumors 0.5-1 cm in diameter were imaged with 18F-FDG, and tumor to liver ratios (TLRs) were calculated. The radiotoxicity of 18F-FDG administration was determined in healthy mice. PyMT mice with small (0.15-0.17 cm) and large (more than 1 cm) tumors were treated with 2-4 mCi of 18F-FDG, and control C3H/B6 mice with 3 mCi of 18F-FDG. At 10 days after treatment the tumors and control mammary glands were analyzed for the presence of apoptotic and necrotic cells. Five patients with breast cancer and metastatic disease were evaluated and standardized uptake values (SUVs) in tumors, maximum tolerated dose, and the doses to the tumor were calculated. RESULTS: Doses up to 5 mCi proved to be non-radiotoxic to normal organs. The 18F-FDG uptake in mouse tumors showed an average TLR of 1.6. The treatment of mice resulted in apoptotic cell death in the small tumors. Cell death through the necrotic pathway was seen in large tumors, and was accompanied by tumor fragmentation and infiltration with leukocytes. Normal mammary tissues were not damaged. A human 18F-FDG dose delivering 200 rad to the red marrow (less than 5% damage) was calculated to be 4.76 Ci for a 70 kg woman, and the dose to the tumors was calculated to be 220, 1100 and 2200 rad for SUVs of 1, 5 and 10, respectively. CONCLUSION: We have shown that positrons delivered by 18F-FDG to mammary tumors have a tumoricidal effect on cancer cells. The study of breast cancer patients suggests that the tumor and normal organ dosimetry of 18F-FDG makes it suitable for therapy of this malignancy.

Animals↗

The role of positron emission tomography in gastrointestinal imaging.

Although the use of PET in studies of the gastrointestinal tract is still relatively new, its value is clear. The future will provide a better definition of the indications for PET, refinement of the technology, and its relative value compared with other modalities such as peptide and antibody imaging, CT, MR imaging, and US.

Antibodies, Neoplasm↗

18F-fluorodeoxyglucose positron emission tomography in small-cell lung cancer.

Positron emission tomography (PET) imaging is not used routinely in small-cell lung cancer (SCLC) but has been proven useful in non-small-cell lung cancer. The performance of (18)F-fluorodeoxyglucose (FDG)-PET in patients with SCLC was evaluated in this study. Fifteen patients with proven SCLC were evaluated (8 men and 7 women; mean age, 68 years; range, 50-81 years). Among the 15 patients with SCLC, 3 were newly diagnosed and 12 had received chemotherapy or radiation therapy before PET. Five patients underwent surgery (3 newly diagnosed and 2 after therapy) after PET scan, and 14 received chemotherapy, radiation therapy, or both. The patient who was not treated with chemotherapy or radiation therapy underwent surgery only. All patients had computed tomographic (CT) scans before PET and had clinical follow-up for at least 2 months after PET. The patients received 3.4 to 4.15 mCi of (18)F-FDG intravenously after fasting for at least 4 hours. Whole-body PET scans were acquired approximately 50 min after injection by using an ADAC Laboratories C-PET plus scanner. Among the 12 patients treated before PET, 2 were found with solitary pulmonary nodules positive on PET. Subsequent surgical resection and pathology showed 1 true positive and 1 false positive (postradiation pneumonitis). Six of these 12 patients had extrapulmonary metastases or large intense hilar or pulmonary uptake on PET, or both. Four of these 12 had no evidence of abnormal FDG uptake and were considered true negatives. The 3 patients with newly diagnosed SCLC were all true positives on PET, confirmed by surgery. One false negative on CT scan was attributed to postradiation fibrosis. These preliminary data suggest that whole-body FDG-PET can provide the basis for determining which treatment modality would be the most appropriate during the early stages of SCLC, when surgery is still an option, and it is a useful tool to assess the effect of treatment in patients with this disease. A more accurate assessment of SCLC will be possible if FDG-PET scan is combined with CT during the early evaluation of these patients.

Aged↗