Joseph C. Hung

Operational Characteristics of 11C-Choline Positron Emission Tomography/Computerized Tomography for Prostate Cancer with Biochemical Recurrence After Initial Treatment

PURPOSE We examined the performance of (11)C-choline positron emission tomography/computerized tomography for its ability to delineate prostate cancer distribution and extent after initial therapy. MATERIALS AND METHODS A consecutive series retrospective review was performed of all patients with prostate cancer who were evaluated using (11)C-choline positron emission tomography/computerized tomography from September 2007 to November 2010 at the Mayo Clinic. Statistical analysis was performed to determine the sensitivity, specificity, positive predictive value, negative predictive value and prostate specific antigen threshold for the detection of recurrent lesions. RESULTS In the study period 176 patients with biochemical recurrence after primary treatment failure underwent (11)C-choline positron emission tomography/computerized tomography. Using patient based analysis (11)C-choline positron emission tomography yielded a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 76%, 91% and 81%, respectively. Of the 176 positron emission tomography/computerized tomography scans performed 56 (32%) were deemed clinically useful as defined by the ability to identify lesions not delineated using conventional imaging, thereby prompting changes in clinical management. The optimal prostate specific antigen for lesion detection was 2.0 ng/ml. On multivariate analysis prostate specific antigen at positron emission tomography (HR 1.37, p = 0.04) and clinical stage at initial diagnosis of prostate cancer (HR 5.19, p = 0.0035) were significant predictors of positive (11)C-choline positron emission tomography/computerized tomography. CONCLUSIONS (11)C-choline positron emission tomography/computerized tomography performs well in men with biochemical recurrence after primary treatment failure. The optimal prostate specific antigen value for lesion detection is approximately 2.0 ng/ml. We found that (11)C-choline positron emission tomography/computerized tomography substantially enhances the rate of prostate cancer lesion detection by approximately 32% beyond what can be garnered using conventional imaging techniques and at a lower prostate specific antigen value.

18F-FDG labelling of human leukocytes

Radiolabelled leukocytes are useful for the imaging of inflammation and infection, and 18F-fluorodeoxyglucose (18F-FDG) is known to concentrate in metabolically active cells. We evaluated the feasibility of leukocyte labelling with 18F-FDG using ACD and heparin anticoagulants at 20°C and 37°C, with and without gentle mixing during incubation. With leukocytes (WBC) harvested from 20 ml blood, studies were performed using 18F-FDG in concentrations of 3.7-74 MBq (0.1-2.0 mCi). 18F-FDG WBC stability in platelet-poor plasma was assessed at 1-4 h. Satisfactory labelling efficiency was achieved with incubation in heparin-saline at 37°C for 30 min (62.7±1.6%), and was further enhanced by mixing during incubation (78.1±3.9%). Cell labelling was predominantly of granulocytes (78.5±1.4%). 18F-FDG WBC was relatively stable in platelet-poor plasma for up to 4 h, and no cell staining was observed in viability studies using trypan blue. These results indicate the feasibility of leukocyte labelling with 18F-FDG, providing an approach that may be useful in PET imaging of inflammation and infection.

Radiopharmaceutical-related pitfalls and artifacts.

The primary goal of this review article is to increase the readers knowledge and understanding of problems associated with the radiopharmaceuticals commonly used in daily practice. To achieve this objective, problems related to the commonly used radiopharmaceuticals are divided into pitfalls and artifacts related to radiopharmaceutical preparation (technetium-99m [99mTc]-labeled and non-99mTc-labeled radiopharmaceutical) and those related to radiopharmaceutical administration. For the radiopharmaceutical formulation-associated pitfalls and artifacts, problems are discussed in terms of factor categories, such as factors associated with radionuclides, factors associated with components, factors associated with preparation procedures, and miscellaneous factors. As for the pitfalls and artifacts caused by radiopharmaceutical administration, these problems are categorized into errors associated with administration technique and nontechnical errors. Clinical manifestations (ie, appearance upon imaging) from the numerous literature-based examples are presented. The effect of the causative factors and the reason each factor can result in radiopharmaceutical preparation and administration problems are discussed. In addition, the possible preventive actions are presented for each group. However, the cause of some pharmaceutical related problems may not be easily recognized, and thus it is difficult to develop preventive and/or corrective plans for these cases.

Biodistribution and dosimetry of [18F]fluorodeoxyglucose labelled leukocytes in normal human subjects

This study was performed in order to assess [18F]fluorodeoxyglucose white blood cell (18F-FDG WBC) dosimetry in normal human subjects. Using previously reported methods, mixed cell suspensions of autologous leukocytes were prepared from four normal volunteers. Leukocytes were labelled in heparin-saline by incubation with 18F-FDG at 37°C for 20 min. After washing and resuspension, 18F-FDG WBCs (225-315 MBq) were administered by intravenous injection. Whole-body imaging was performed at 0.5, 1, 2, 4 and 6 h using a GE Varicam with 511 keV collimation. Blood samples were obtained at corresponding times as well as fractionated urinary collection. Whole-body anterior and posterior images were used for calculation of organ dosimetry. Uptake of 18F-FDG WBCs occurred predominantly within the reticulo-endothelial system. Plasma activity, urinary excretion (9.9±2.3% at 6 h), and brain uptake (1.7±0.4%) were consistent with partial elution of 18F-FDG. Positron emission tomography imaging performed at5-6 h after injection yielded good quality images of reticulo-endothelial uptake. Whole-body and organ dosimetry for 18F-FDG WBCs in doses of 225-250 MBq are comparable with reported results for conventional doses of 111In oxine labelled leukocytes. Further studies of 18F-FDG WBC as an agent for positron emission tomography imaging of inflammatory disease appear warranted.

Evaluation of Macroaggregated Albumin Particle Sizes for Use in Pulmonary Shunt Patient Studies

OBJECTIVE To assess commercial macroaggregated albumin (MAA) reagent kits for compliance with particle-size parameters needed for proper clinical evaluation of pulmonary shunts (right-to-left). DESIGN Comparative trial. SETTING Nuclear pharmacy (laboratory setting). PATIENTS AND OTHER PARTICIPANTS Not applicable. INTERVENTIONS Minimally, 90% of the particles contained within an MAA reagent kit should be within the 10 to 90 microns range with minimal variation in particle size distribution and as few small particles (i.e., < 10 microns) as possible. Five separate vials from five commercial brands of MAA reagent kits were obtained, and 500 to 517 particles were analyzed for each sample. An additional study was performed on one of the MAA reagent kit brands, using five vials from each of five different lot numbers to determine the variability between lots. MAIN OUTCOME MEASURES Long axis (maximum, micron), short axis (minimum, micron), and the area (micron 2) of each MAA particle. RESULTS One MAA brand had the lowest percentage of unacceptable MAA particle sizes and maintained consistent particle sizes between vials. However, the same MAA reagent kit brand showed that only two of five lots had a low percentage of MAA particle sizes below the 10-micron limit. CONCLUSION Particle sizes varied among the five different brands of MAA reagent kits, as did different lots of the best-performing kit. This variability in particle sizes may affect the accuracy and reproducibility of pulmonary shunt patient studies.

Pulmonary Function Monitoring During Adenosine Myocardial Perfusion Scintigraphy in Patients With Chronic Obstructive Pulmonary Disease

OBJECTIVE To determine whether adenosine could be safely administered to patients with chronic obstructive pulmonary disease (COPD) for coronary vasodilatation during perfusion scintigraphy without causing bronchospasm. MATERIAL AND METHODS The study was divided into two phases. In the monitoring phase, patients with COPD were pretreated with an inhaled bronchodilator (albuterol) and had pulmonary function monitored during the infusion of a graduated dose of adenosine. Eligibility for entry into this phase of the study was determined on the basis of results of pulmonary function testing (PFT) during resting. Once we had shown that adenosine could be safely administered to patients with COPD, an implementation phase was begun. Entry did not require resting PFT, and patients were administered adenosine without monitoring of pulmonary function. Differences between patients with normal pulmonary function or mild COPD and those with more severe COPD were analyzed statistically. RESULTS Of 94 patients entered into the monitoring phase, none had obvious bronchospasm. The dosage of adenosine was reduced in four patients because of a decrease in forced expiratory volume in 1 second (FEV1) of 20% in comparison with baseline (FEV1 before administration of albuterol). The mean FEV1 decreased slightly from 1.83 L after administration of albuterol to 1.78 L during the maximal adenosine dose. Patients with a remote history of asthma, positive result of a methacholine challenge test, or mild COPD (FEV1 60 to 80% of the maximal predicted value for age) did not differ significantly in their response to infusion of adenosine from those with moderate or severe COPD (FEV1 30 to 59% of the maximum predicted for age). Of 117 patients in the implementation phase, 2 had bronchospasm during infusion of adenosine that was quickly terminated by stopping the administration in one patient and reducing the dose of adenosine in the other. CONCLUSION This study shows that adenosine can be safely administered intravenously to selected patients with known or suspected COPD to produce coronary vasodilatation for myocardial perfusion imaging. Patients who are within the guidelines established for this study should be considered for adenosine coronary vasodilatation with use of bronchodilator pretreatment, a graduated dose of adenosine, and regular chest auscultation during the infusion.

Activated charcoal as a potential radioactive marker for gastrointestinal studies.

The scintigraphic measurement of colonic transit is currently performed using 111In ion exchange resin pellets delivered to the colon in a capsule coated with a pH sensitive polymer, methacrylate, which dissolves in the distal ileum. However, in the USA, this requires an investigational drug permit. Our aim was to evaluate the in vitro binding characteristics of activated charcoal in milieus that mimicked gastric and small intestinal content. The in vitro incubation of activated charcoal was performed with Na99Tc(m)O4, 99Tc(m)-DTPA, 111InCl3, 111In-DTPA, 201TlCl and 67Ga-citrate in the pH range 2-4 and pH 7.2 at 37 degrees C. We estimated the association of radiopharmaceuticals with the activated charcoal over a 3 h in vitro incubation. With the exception of 67Ga-citrate, the association of activated charcoal with the other radiopharmaceuticals was approximately 100% throughout the 3 h incubation. In conclusion, activated charcoal appears to adsorb avidly with common radioisotopes, and appears promising as an alternative to resin ion exchange pellets used for the measurement of gastrointestinal transit by scintigraphy.

Optimal conditions of 99mTc eluate for the radiolabeling of 99mTc-sestamibi

Our nuclear pharmacy has reported that a failed radiochemical purity (RCP) (i.e., RCP < 90%) of 99mTc-sestamibi may be associated with the use of a first elution at later stages from a long-ingrowth time (i.e., > or = 72 h) wet-column generator. The primary purpose of this study was to evaluate the effects of 99mTc eluates from wet- and dry-column generators on the RCP of 99mTc-sestamibi under the above conditions. RCP values were found to be measurably higher and kit failure rates lower with the use of dry-column generator eluate. Using a dry-column generator eluate, Cardiolite kits were prepared with 11.10 GBq of 99mTc at 3, 4, and 5 h postelution and 5.55 GBq at 6, 10, 11, and 12 h postelution. Our data suggest that when 11.10 GBq of 99mTc from a dry-column generator with > or = 72-h ingrowth was used to prepare 99mTc-sestamibi, kit failure started to occur using 99mTc eluate at approximately 4 h postelution. When 5.55 GBq was used to reconstitute the kit, RCP failure began to occur using 99mTc eluate approximately 10 h postelution and wet-column generators; the failure rate can be reduced even further by avoiding the addition of high activities of 99mTc and long elution times.

The planning and design of a new PET radiochemistry facility

The objectives of the Mayo positron emission tomography (PET) radiochemistry facility are the production of PET drugs for clinical service of our in-house patients, commercial distribution of PET drug products, and development of new PET drugs. The factors foremost in the planning and design phases were the current regulatory climate for PET drug production, radiation safety issues, and effective production flow. A medium-energy cyclotron was preferred for its small footprint to allow a compact vault, its high-proton energy to offer a higher product radioactivity; and its research capabilities. A vault installation was chosen instead of a self-shielded machine for improved access and ease of maintenance. Adjacent to the cyclotron is an area that houses the support equipment and a large dedicated workshop to support machine maintenance and targetry development. The total floor area of the PET radiochemistry facility is 344.2 m(2) (3,705.5 ft(2)), of which the radiochemistry laboratory occupies 130.7 m(2) (1,407 ft(2)). To reduce environmental contamination of PET drug products, the laboratory contains a controlled-air environment class 10,000 (M5.5) clean room with access via an interlocking entry change area. A fully shielded isolator (class 100 [M3.5]) is located in the clean room. The PET drugs are delivered via shielded tubing between the synthesizer and isolator. Inside the isolator, there is an automated device for dispensing the PET drug into either a bulk-activity vial or a unit-dose syringe. The dispensed PET radiopharmaceutical then passes through a hatch to a dedicated area where it is packaged for in-house use or commercial distribution. Unit doses for in-house patients are transported via pneumatic tube to the PET imaging area 76.2 m (250 ft) away. There is extensive radiation area monitoring throughout the facility that continuously measures radiation levels. We believe that our new PET radiochemistry facility not only meets overall objectives, but also provides an ergonomic, efficient working environment for the production and development of PET drugs.

The radiation dosimetry and normal value study of 99mTc-HMPAO-labeled leukocytes.

RATIONALE AND OBJECTIVES.Indium-111 (111In)—labeled leukocyte scanning has been used frequently in patients suspected of having infections. Recently, technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) has been used to label leukocytes. This study was undertaken to determine the distribution and dosimetry of 99mTc-HMPAO leukocytes in healthy subjects. METHODS.Five healthy volunteers had leukocytes labeled with 99mTc-HMPAO. After injection of the labeled leukocytes, whole body images and blood and urine samples were obtained at multiple time points. RESULTS.Visual interpretation of the images demonstrated significant bowel activity as early as 2 hours and increasing with time such that on the 8- and 24-hour images, the amount of bowel activity would preclude using 99mTc-HMPAO leukocyte scanning for abdominal processes. The dosimetry for this study is similar to that of other studies and is in an acceptable diagnostic range. CONCLUSIONS.99mTc-HMPAO leukocyte studies are an acceptable alternative to 111In-labeled leukocyte studies in terms of dosimetry. Use of such studies in the abdomen should be limited to early images, usually before 2 hours, to avoid confusion with the normal route of excretion in the bowel.