Janet S. Reddin

Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease.

Objective: We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blood flow (CBF), to that of FDG-PET in distinguishing patients with Alzheimer disease (AD) from healthy, age-matched controls. Methods: Fifteen patients with AD (mean age 72 ± 6 years, Mini-Mental State Examination score [MMSE] 20 ± 6) and 19 age-matched controls (mean age 68 ± 6 years, MMSE 29 ± 1) underwent structural MRI. Participants were injected with 5 mCi of FDG during pseudocontinuous ASL scan, which was followed by PET scanning. Statistical parametric mapping and regions of interest (ROI) analysis were used to compare the ability of the 2 modalities in distinguishing patients from controls. Similarity between the 2 modalities was further assessed with linear correlation maps of CBF and metabolism to neuropsychological test scores. Results: Good agreement between hypoperfusion and hypometabolism patterns was observed, with overlap primarily in bilateral angular gyri and posterior cingulate. ROI results showed similar scales of functional deficit between patients and controls in both modalities. Both ASL and FDG-PET were able to distinguish neural networks associated with different neuropsychological tests with good overlap between modalities. Conclusions: Our voxel-wise results indicated that ASL-MRI provides largely overlapping information with FDG-PET. ROI analysis demonstrated that both modalities detected similar degrees of functional deficits in affected areas. Given its ease of acquisition and noninvasiveness, ASL-MRI may be an appealing alternative for AD studies.

Prediction of Survival by [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial

PURPOSE In this prospective National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models. RESULTS Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak. CONCLUSION Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.

Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer's disease

The utility of fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging in Alzheimers disease (AD) diagnosis has been well established. Recently, measurement of cerebral blood flow using arterial spin labeling magnetic resonance imaging (ASL‐MRI) has shown diagnostic potential in AD, although it has never been directly compared with FDG‐PET.

Feasibility of estimation of brain volume and 2-deoxy-2- 18 F-fluoro-D-glucose metabolism using a novel automated image analysis method: Application in Alzheimer's disease

The development of clinically-applicable quantitative methods for the analysis of brain fluorine-18 fluoro desoxyglucose-positron emission tomography ((18)F-FDG-PET) images is a major area of research in many neurologic diseases, particularly Alzheimers disease (AD). Region of interest visualization, evaluation, and image registration (ROVER) is a novel commercially-available software package which provides automated partial volume corrected measures of volume and glucose uptake from (18)F-FDG PET data. We performed a pilot study of ROVER analysis of brain (18)F-FDG PET images for the first time in a small cohort of patients with AD and controls. Brain (18)F-FDG-PET and volumetric magnetic resonance imaging (MRI) were performed on 14 AD patients and 18 age-matched controls. Images were subjected to ROVER analysis, and voxel-based analysis using SPM5. Volumes by ROVER were 35% lower than MRI volumes in AD patients (as hypometabolic regions were excluded in ROVER-derived volume measurement ) while average ROVER- and MRI-derived cortical volumes were nearly identical in control population. Whole brain volumes when ROVER-derived and whole brain metabolic volumetric products (MVP) were significantly lower in AD and accurately distinguished AD patients from controls (Area Under the Curve (AUC) of Receiver Operator Characteristic (ROC) curves 0.89 and 0.86, respectively). This diagnostic accuracy was similar to voxel-based analyses. Analysis by ROVER of (18)F-FDG-PET images provides a unique index of metabolically-active brain volume, and can accurately distinguish between AD patients and controls as a proof of concept. In conclusion, our findings suggest that ROVER may serve as a useful quantitative adjunct to visual or regional assessment and aid analysis of whole-brain metabolism in AD and other neurologic and psychiatric diseases.

Qualification of National Cancer Institute–Designated Cancer Centers for Quantitative PET/CT Imaging in Clinical Trials

The National Cancer Institute developed the Centers for Quantitative Imaging Excellence (CQIE) initiative in 2010 to prequalify imaging facilities at all of the National Cancer Institute–designated comprehensive and clinical cancer centers for oncology trials using advanced imaging techniques, including PET. Here we review the CQIE PET/CT scanner qualification process and results in detail. Methods: Over a period of approximately 5 y, sites were requested to submit a variety of phantoms, including uniform and American College of Radiology–approved phantoms, PET/CT images, and examples of clinical images. Submissions were divided into 3 distinct time periods: initial submission (T0) and 2 requalification submissions (T1 and T2). Images were analyzed using standardized procedures, and scanners received a pass or fail designation. Sites had the opportunity to submit new data for scanners that failed. Quantitative results were compared across scanners within a given time period and across time periods for a given scanner. Results: Data from 65 unique PET/CT scanners across 56 sites were submitted for CQIE T0 qualification; 64 scanners passed the qualification. Data from 44 (68%) of those 65 scanners were submitted for T2. From T0 to T2, the percentage of scanners passing the CQIE qualification on the first attempt rose from 38% for T1 to 67% for T2. The most common reasons for failure were SUV outside specifications, incomplete submission, and uniformity issues. Uniform phantom and American College of Radiology–approved phantom results between scanner manufacturers were similar. Conclusion: The results of the CQIE process showed that periodic requalification may decrease the frequency of deficient data submissions. The CQIE project also highlighted the concern within imaging facilities about the burden of maintaining different qualifications and accreditations. Finally, for quantitative imaging–based trials, further evaluation of the relationships between the level of the qualification (e.g., bias or precision) and the quality of the image data, accrual rates, and study power is needed.

13 Infection Scintigraphy

1. Which of the following is true of 67Ga citrate- and 111In-labeled leukocytes? (a) Both require the use of a medium-energy collimator. (b) Both can be used to effectively image neoplasms and infections. (c) Both have three gamma peaks available for imaging. (d) All of the above. (e) (a) and (b) only. 2. In general, the best radiopharmaceutical to use for a suspected abdominal abscess is: (a) 67Ga citrate (b) 111In-labeled leukocytes (c) 111In satumomab pendetide (d) 111In octreotide 3. For imaging of inflammation or infection, leukocytes may be labeled with: (a) 111In oxine (b) 99mTc exametazime (c) 67Ga citrate (d) All of the above (e) (a) and (b) only

11 Genitourinary System Scintigraphy

1. What is the imaging protocol that was most probably used to obtain the images in Fig. 1? (a) Consecutive 1 s images for 15 s (b) Consecutive 3 s images for 45 s (c) 15 consecutive 10 s images (d) 15 consecutive 15 s images 2. Which of the following describes the activity on delayed static images in a patient with testicular torsion? (a) Decreased (b) Normal (c) Increased (d) Variable 3. Clearance of 99mTc MAG3 is by: (a) Active transport (b) Tubular secretion (c) Glomerular filtration (d) None of the above 4. Which renal imaging agent allows imaging at 6 h after injection? (a) 99mTc MAG3 (b) 99mTc DTPA (c) 99mTc GH (d) 99mTc DMSA

12 Oncologic Scintigraphy

1. How should 99mTc sestamibi be administered when used for breast tumor imaging? (a) Intramammary injection (b) Via indwelling catheter (c) Via intravenous injection in the arm contralateral to involved breast (d) None of the above (e) (b) and (c) 2. What is the optimal scanning time for neoplasm when using 67Ga citrate? (a) 4 h (b) 6 h (c) 24 h (d) 48 h 3. Lymphoscintigraphy is used to: (a) Map lymphatic channels (b) Determine drainage pathways from malignant neoplasms (c) Identify the sentinel node (d) All of the above (e) (a) and (b) only 4. 111In pentetreotide is a: (a) Potassium analog (b) Monoclonal antibody (c) Somatostatin analog (d) Radiocolloid 5. A HAMA response occurs because: (a) A kit contains pyrogens. (b) Monoclonal antibodies are produced from mouse cells which the human body recognizes as a foreign protein. (c) A patient is allergic to 111In. (d) Monoclonal antibodies are produced from human cells that trigger an immune response in the patient. 6. A dose of 111In satumomab pendetide should be _____ before injection. (a) Shielded (b) Filtered (c) Assayed (d) All of the above (e) (a) and (c) only 7. 111In satumomab pendetide is used to image: (a) Extrahepatic metastases from colorectal and ovarian cancer (b) Breast tumors (c) Neuroendocrine tumors (d) Lymphatic channels 8. Advantages of 201Tl chloride over 67Ga citrate include: (a) Much shorter half-life. (b) Less uptake in inflammatory processes. (c) Imaging may take place sooner. (d) All of the above. (e) (b) and (c) only. 9. It is possible to use 99mTc sestamibi for breast tumor imaging because there is no uptake of sestamibi in the normal breast. (a) True (b) False 10. A monoclonal antibody is developed which displays cross-reaction. This means: (a) The antibody triggers an immune response in the patient. (b) The antibody will bind antigens other than the one it was formed with. (c) The antibody can be labeled with either 99mTc or 111In. (d) None of the above. 11. Examples of neuroendocrine tumor include: (a) Pituitary adenoma (b) Small-cell lung cancer (c) Neuroblastomas (d) All of the above (e) (a) and (c) only 12. Visualization of kidneys at 48 h is _____on a scan using 111In pentetreotide and _____on a 67Ga citrate scan. (a) Normal, abnormal (b) Abnormal, normal (c) Normal, normal (d) Abnormal, abnormal 13. 18FDG can be used to image tumors because the glycolytic rate is higher in tumor than in normal tissues. (a) True (b) False 14. Which of the following are true regarding 18FDG tumor imaging? (a) PET scanning is required. (b) The patient should fast before the exam. (c) Only brain tumors can be detected. (d) All of the above. (e) All except c. 15. On a Monday morning, a technologist learns that a patient needs to be scheduled for imaging with 67Ga citrate and also a lower GI. If the ordering physician wishes that both exams be done within the week, how should these studies be scheduled? (a) Lower GI on Monday morning and 67Ga citrate on Monday afternoon. (b) Lower GI on Monday morning and 67Ga citrate on Wednesday. (c) 67Ga injection on Monday morning followed by imaging each day and lower GI at noon on Friday. (d) Inject patient with 67Ga citrate on Monday morning, send for lower GI, and then perform first imaging of gallium on Monday afternoon. 16. Pheochromocytomas are imaged using: (a) 131I MIBG (b) 131I NP-59 17. The use of PET imaging in oncology takes advantage of the _____differences between normal and neoplastic tissue. (a) Structural (b) Metabolic (c) Density (d) Hormonal 18. Hodgkin’s disease is a type of: (a) Lung cancer (b) Lymphoma (c) AIDS (d) Lupus 19. Normal areas of uptake for 67Ga citrate include all of the following except: (a) Intestinal mucosa (b) Parathyroid glands (c) Liver (d) Epiphyses in pediatric patients 20. If a low-energy collimator is used for imaging 67Ga, what will the effect be? (a) There is increased septal penetration. (b) Poor spatial resolution. (c) Decreased sensitivity. (d) (a) and (c). (e) (a) and (b). 21. F-18 fluciclovine is currently an FDA-approved imaging agent for what type of cancer? (a) Thyroid cancer (b) Lung cancer (c) Liver cancer (d) Prostate cancer 22. What is the half-life of Ga-68 dotatate? (a) 68 min (b) 78 h (c) 6 h (d) 110 min 23. Recommended dose for imaging with Ga-68 dotatate? (a) 10 mCi (b) 15 mCi (c) 20 mCi (d) 0.054 mCi/kg up to 5.4 mCi 24. Gallium-68 is ___________ produced. (a) Generator (b) Cyclotron 25. Gallium-68 dotatate is indicated for imaging what type of cancers utilizing PET? (a) Small-cell lung cancer (b) Neuroendocrine tumors (c) Prostate cancer (d) Breast cancer 26. Recommended dose for imaging with F-18 fluciclovine? (a) 10 mCi (370 MBq) (b) 5 mCi (c) 20 mCi

Appendix 15 Answers to Chapter 15

1. (d) 131I is used to treat thyroid cancer and hyperthyroidism by ablation. Grave’s disease is the most common cause of hyperthyroidism. 2. (a) The intramuscular injection of nonradioactive B12 is given to preload the liver and to saturate receptor sites in plasma so that the portion of radioactive B12 absorbed will be passed through the urine. 3. (d) 32P chromic phosphate is a bluish green colloid and is used for intracavitary therapy. 32P sodium phosphate is a clear solution that is used to treat polycythemia vera and bone pain from metastasis and is administered intravenously. 32P is a beta emitter. 4. (b) As with all radioactive materials, 89Sr should be assayed prior to administration. However, the NRC allows administration of 89Sr unit doses without assay because not all dose calibrators assay them accurately. 5. (b) See explanation for question 3. 6. (c) 32P chromic phosphate is useful in treating malignant ascites. 32P sodium phosphate is used to treat polycythemia vera. 89Sr (as well as 32P sodium phosphate and 153Sm-EDTMP) is used to treat malignant bone pain by localizing where there is bone mineral turnover. 131I may be used to treat Grave’s disease. 7. (c) 89Sr chloride can be administered by direct venous access, but as it is a beta emitter, it is a better option to access the vein with an intravenous line and check the patency of the system before injection. If the dose is infiltrated into the tissue surrounding the vein, the tissue will be unnecessarily irradiated. 8. (b) 89Sr and 32P are beta emitters and will be effectively shielded with the plastic syringe. Using a lead syringe shield will cause bremsstrahlung. 9. (b) See explanation to question 6. 10. (b) Intrinsic factor is a glycoprotein. It is secreted by the gastric mucosa, and without it vitamin B12 cannot be absorbed. If a Schilling test shows a B12 deficiency, the test can be repeated with the intrinsic factor to determine if the lack of it is the cause of malabsorption. 11. (b) The radioactivity in the urine represents the amount of vitamin B12 absorbed. The labeled B12 is excreted through the urine, so if any urine is not collected, the percent excretion will be falsely low. 12. (c) The results from the first 24-h sample collected during Stage I are abnormal (normal is >8–10%), and the result from Stage II is 12%, which is normal. This indicates that the addition of intrinsic factor has corrected the malabsorption, meaning the patient has pernicious anemia, which is a vitamin B12 deficiency resulting from lack of intrinsic factor. There are other causes of B12 which include low intake, pancreatic insufficiency, and various medications. 13. (d) To calculate the percent excreted, one uses the following formula:

Appendix 2 Answers to Chapter 2

1. (b) 201Tl decays by electron capture with gamma emissions of 0.135 MeV and 0.167 MeV. 2. (c) Stannous chloride is a reducing agent which changes the valence state of Tc in pertechnetate. It has no effect on either the amount of Al3+ or the radiation dose. 3. (b) The half-life of 131I is 8.06 days. Since the time elapsed is about two half-lives, the original activity would be halved twice (50 mCi/2 = 25 mCi, 25 mCi/2 = 12.5 mCi). 4. (b) 20 mCi × 0.62 = 12.4 mCi 5. (d) To find the effective half-life, we use the formula