Richard E. Wendt

The Safety of Lymphatic Mapping in Pregnant Breast Cancer Patients Using Tc‐99m Sulfur Colloid

Abstract:  This investigation was undertaken to assess the risk to the embryo/fetus associated with sentinel lymph node biopsy and lymphoscintigraphy of the breast performed in pregnant patients. Approximately 92.5 MBq (2.5 mCi) of filtered Tc‐99m sulfur colloid was injected peritumorally the day before surgery in two nonpregnant women with breast cancer. The whole‐body distribution of the radiopharmaceutical was evaluated using a gamma camera 1 hour after injection. We then calculated the absorbed dose to the embryo/fetus for three theoretical extreme scenarios of biodistribution and pharmacokinetics: 1) all of the injected radiopharmaceutical remains in the breast and is eliminated only by physical decay; 2) all of the injected radiopharmaceutical is instantaneously transported to the urinary bladder, where it remains and is eliminated only by physical decay; and 3) the injected radiopharmaceutical behaves as though it were administered intravenously, that is, it has the biodistribution and pharmacokinetics of Tc‐99m sulfur colloid injected for a liver/spleen or bone marrow scan. The fetal radiation absorbed dose was then estimated for two Tc‐99m dosages: 18.5 MBq (0.5 mCi) and 92.5 MBq (2.5 mCi). The Medical Internal Radiation Dosimetry (MIRD) program was used to estimate the absorbed doses to the embryo/fetus for the first two scenarios. Published data were used to calculate the doses for the third scenario. A single breast is not among the source organs in the MIRD program, so the heart was used as a surrogate in the first scenario. In the two breast cancer patients, whole‐body gamma‐camera images obtained 1 hour after radiopharmaceutical injection revealed no radioactivity except in the vicinity of the injection site. In the theoretical scenarios, with 92.5 MBq, the highest absorbed doses to the embryo/fetus were as follows: scenario 1, 7.74 × 10−2 mGy at 9 months of pregnancy; scenario 2, 4.26 mGy during early pregnancy; and scenario 3, 0.342 mGy at 9 months of pregnancy. The maximum absorbed dose to the fetus of 4.3 mGy calculated for the worst‐case scenario is well below the 50 mGy that is believed to be the threshold absorbed dose for adverse effects. Thus breast lymphoscintigraphy during pregnancy appears to present a very low risk to the embryo/fetus. 

Changes in intervertebral disc cross-sectional area with bed rest and space flight

Study Design. We measured the cross-sectional area of the intervertebral discs of normal volunteers after an overmight rest; before, during, and after 5 or 17 weeks of bed rest; and before and after 8 days of weightiessness. Objectives. This study sought to determine the degree of expansion of the lumbar discs resulting from bed rest and space flight. Summary of Background Data. Weightlessness and bed rest, an analog for weightlessness, reduce the mechanical loading on the musculoskeletal system. When unioded, intervertebral discs will expand, increasing the nutrtional diffusion distance and altering the mechancial properties of the spine. Methods. Magnetic resonance imaging was used to measure the cross-sectional area and transverse relaxation time (T2) of the intervertebral discs. Results. Overnight or longer bed rest causes expansion of the disc area, which reaches an equilibrium value of about 22% (range 10–40%) above baseline within 4 days. Increases in disc area were associated with modest increases in disc T2. During bed rest, disc height increased approximately 1 mm, about one-half of previous estimates based on body height measurements. After 5 weeks of bed rest, disc area returned to baseline within a few days of ambulation, whereas after 17 weeks, disc area remained above baseline 6 weeks after reambulation. After 8 days of weightlessness, T2, disc area, and lumbar length were not significantly different from baseline values 24 hours after landing. Conclusions. Significant adaptive changes in the intervertebal discs can be expected during weightlessness. These changes, which are rapidly reversible after short duration flights, may be an important factor during and after long-duration missions.

AAPM Task Group 108: PET and PET/CT Shielding Requirements

The shielding of positron emission tomography (PET) and PET/CT (computed tomography) facilities presents special challenges. The 0.511 MeV annihilation photons associated with positron decay are much higher energy than other diagnostic radiations. As a result, barrier shielding may be required in floors and ceilings as well as adjacent walls. Since the patient becomes the radioactive source after the radiopharmaceutical has been administered, one has to consider the entire time that the subject remains in the clinic. In this report we present methods for estimating the shielding requirements for PET and PET/CT facilities. Information about the physical properties of the most commonly used clinical PET radionuclides is summarized, although the report primarily refers to fluorine-18. Typical PET imaging protocols are reviewed and exposure rates from patients are estimated including self-attenuation by body tissues and physical decay of the radionuclide. Examples of barrier calculations are presented for controlled and noncontrolled areas. Shielding for adjacent rooms with scintillation cameras is also discussed. Tables and graphs of estimated transmission factors for lead, steel, and concrete at 0.511 MeV are also included. Meeting the regulatory limits for uncontrolled areas can be an expensive proposition. Careful planning with the equipment vendor, facility architect, and a qualified medical physicist is necessary to produce a cost effective design while maintaining radiation safety standards.

Electrocardiographic gating and monitoring in NMR imaging

ECG gating and monitoring during NMR imaging may be achieved reliably by applying the principles in this tutorial. In order to use the ECG signal both for triggering and for patient monitoring it must have a prominent R-wave, while at the same time must have little artifact from gradient switches or the Lorentz voltage across the aorta, and not be significantly distorted by gradient switching artifacts. The twin goals of no image artifacts and minimal ECG artifacts may be achieved by the following means: (1) using ECG electrodes with minimal metal, (2) selecting electrodes and cables with no ferrous metals, (3) placing the limb electrodes close together, (4) placing the line between the limb electrodes and the leg electrode parallel to the magnetic flux lines and, if possible, parallel to the transverse component of the gradient flux lines, (5) keeping the area between the limb electrodes and the leg electrode small, (6) placing that area in the center of the imager and (7) twisting or braiding the cables. Following these principles allows artifact-free images and reliable ECG monitoring during ECG-gated NMR imaging examinations.

Dosimetry of high dose skeletal targeted radiotherapy (STR) with 166Ho-DOTMP

A study was undertaken to determine the maximum tolerated dose of (166)Ho-DOTMP that could be administered safely, without negatively impacting marrow re-engraftment, in patients with multiple myeloma treated with melphalan prior to transplant. Ho-166 DOTMP is a tetraphosphonate that localizes rapidly to bone surface. The Ho-166 physical half-life is 26.8 hr and the maximum beta energy is 1.8 MeV. Standard dosimetry models were adapted for radiation absorbed dose estimates using data obtained from whole body counting of the low abundance photons emitted by (166)Ho. Eighty-three patients received high dose (166)Ho-DOTMP followed by melphalan and transplant of peripheral blood stem cells. Twenty-five patients also received 8 Gy total body radiation (TBI). Dosages administered ranged from 460 to 4476 mCi (166)Ho-DOTMP. Marrow dose was derived using the assumption that all radioactivity not excreted by 20 hours was localized to the bone surfaces, and applying the Eckerman bone and marrow dose model to the calculated bone residence times. The dosimetry of the urinary bladder and kidneys was important because of the rapid excretion of the non-targeted radioactivity via the urinary pathway. The dynamic bladder model was used for bladder wall surface dose, and the ICRP 53 kinetic model was used to model kidney kinetics with an additional blood component included. Marrow doses ranged from 13 to 59 Gy and successful hematapoietic recovery occurred. Bladder doses ranged from 4.7 to 157 Gy. Hemorrhagic cystitis occurred in some patients who received more than 40 Gy to the bladder wall surface. Bladder irrigation was successful in protecting patients from bladder toxicity. Kidney doses ranged from 0.5-7.9 Gy. Kidney toxicity in the form of thrombotic microangiopathy with renal dysfunction was observed, with the severity being related to Ho-166-DOTMP radiation dose and probably the dose rate as well. In a future trial, kidney dosimetry will be assessed using early serial gamma camera imaging and modifications will be implemented to reduce renal toxicity.

Characterization of acute myocardial infarction by magnetic resonance imaging

The T2-weighted spin-echo technique is currently the most frequently used magnetic resonance imaging (MRI) method to visualize acute myocardial infarction. However, image quality is often degraded by ghost artifacts from blood flow, and respiratory and cardiac contractile motion. To enhance the usefulness of this technique for detailed characterization of infarction, a velocity-compensated spin-echo pulse sequence was tested by imaging a flow phantom, 6 normal subjects and 17 patients with acute myocardial infarction. After preliminary studies were performed in 7 patients to determine optimal imaging parameters, a standardized imaging protocol was used in the next 10. The location of myocardial infarction identified by the electrocardiogram and coronary anatomy was correctly identified in 10 of 10 patients. Distribution of the injury within the left ventricle was clearly visualized, and showed that patients often had a mixture of transmural and nontransmural injury. Heterogenous distribution of signal intensity within the infarction suggested the presence of hemorrhage. Papillary muscle involvement was readily apparent. Signal intensity of the infarction (brightest segment) was increased by 89 +/- 31% compared with the mean of the remote segments. The myocardial/skeletal muscle ratio was significantly (p less than 0.001) increased for the infarction segments compared with that for remote myocardium, allowing quantitative analysis of segmental signal intensity. The MRI wall motion study obtained as part of this protocol demonstrated wall thickening in 58% of the infarction segments and in 6 of 10 patients. This finding suggested the presence of reversibly injured myocardium. In conclusion, the results demonstrate the potential of MRI for detailed tissue characterization after acute myocardial infarction.

Observed intercamera variability in clinically relevant performance characteristics for Siemens Symbia gamma cameras

We conducted an evaluation of the intercamera (i.e., between cameras) variability in clinically relevant performance characteristics for Symbia gamma cameras (Siemens Medical Solutions, Malvern, PA) based on measurements made using nine separate systems. The significance of the observed intercamera variability was determined by comparing it to the intracamera (i.e., within a single camera) variability. Measurements of performance characteristics were based on the standards of the National Electrical Manufacturers Association and reports 6, 9, 22, and 52 from the American Association of Physicists in Medicine. All measurements were performed using T99mc (except C57o used for extrinsic resolution) and low‐energy, high‐resolution collimation. Of the nine cameras, four have crystals 3/8 in. thick and five have crystals 5/8 in. thick. We evaluated intrinsic energy resolution, intrinsic and extrinsic spatial resolution, intrinsic integral and differential flood uniformity over the useful field‐of‐view, count rate at 20% count loss, planar sensitivity, single‐photon emission computed tomography (SPECT) resolution, and SPECT integral uniformity. The intracamera variability was estimated by repeated measurements of the performance characteristics on a single system. The significance of the observed intercamera variability was evaluated using the two‐tailed F distribution. The planar sensitivity of the gamma cameras tested was found be variable at the 99.8% confidence level for both the 3/8‐in. and 5/8‐in. crystal systems. The integral uniformity and energy resolution were found to be variable only for the 5/8‐in. crystal systems at the 98% and 90% confidence level, respectively. All other performance characteristics tested exhibited no significant variability between camera systems. The measured variability reported here could perhaps be used to define nominal performance values of Symbia gamma cameras for planar and SPECT imaging. PACS numbers: 87.62.+n, 87.58.Pm, 87.58.Ce

Detection of viable myocardium in segments with fixed defects on thallium-201 scintigraphy: usefulness of magnetic resonance imaging early after acute myocardial infarction.

To determine if magnetic resonance imaging (MRI) can be used to detect tissue viability in segments with persistent 201T1 defects early following acute myocardial infarction, 24 patients underwent MRI and adenosine 201T1 single photon emission computed tomography (SPECT) imaging at approximately 6 days. Infarction was demonstrated on MRI using a velocity-compensated, T2-weighted spin-echo pulse sequence. Wall thickening was assessed using a gradient-echo pulse sequence obtained in the same anatomic position. Viable myocardium was defined by MRI as a segment with increased signal intensity and preserved wall thickening. A fixed defect on the 201T1 SPECT images was defined as the absence of any redistribution 4 hours after the 201T1 infusion. Of 11 patients with redistribution on the 201T1 images in the infarction region, 10 (91%) had preserved wall thickening by MRI. Of 13 patients with fixed defects on the 201T1 images in the infarction region, 6 (46%) had preserved wall thickening by MRI. Of 7 patients with absent thickening, all had one or more segments with absent perfusion on redistribution imaging. Wall thickening tended to occur in patients who received thrombolytic therapy or who underwent revascularization procedures prior to imaging. The results of the present study suggest that spin-echo MRI with motion compensation can be used to identify viable myocardium in patients with fixed defects on 201T1 SPECT following acute myocardial infarction.

Whole-Body Biodistribution Kinetics, Metabolism, and Radiation Dosimetry Estimates of 18F-PEG6-IPQA in Nonhuman Primates

We recently developed the radiotracer 4-[(3-iodophenyl)amino]-7-(2-[2-{2-(2-[2-{2-(18F-fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]-quinazoline-6-yl-acrylamide) (18F-PEG6-IPQA) for noninvasive detection of active mutant epidermal growth factor receptor kinase-expressing non–small cell lung cancer xenografts in rodents. In this study, we determined the pharmacokinetics, biodistribution, metabolism, and radiation dosimetry of 18F-PEG6-IPQA in nonhuman primates. Methods: Six rhesus macaques were injected intravenously with 141 ± 59.2 MBq of 18F-PEG6-IPQA, and dynamic PET/CT images covering the thoracoabdominal area were acquired for 30 min, followed by whole-body static images at 60, 90, 120, and 180 min. Blood samples were obtained from each animal at several time points after radiotracer administration. Radiolabeled metabolites in blood and urine were analyzed using high-performance liquid chromatography. The 18F-PEG6-IPQA pharmacokinetic and radiation dosimetry estimates were determined using volume-of-interest analysis of PET/CT image datasets and blood and urine time–activity data. Results: 18F-PEG6-IPQA exhibited rapid redistribution and was excreted via the hepatobiliary and urinary systems. 18F-PEG6 was the major radioactive metabolite. The critical organ was the gallbladder, with an average radiation-absorbed dose of 0.394 mSv/MBq. The other key organs with high radiation doses were the kidneys (0.0830 mSv/MBq), upper large intestine wall (0.0267 mSv/MBq), small intestine (0.0816 mSv/MBq), and liver (0.0429 mSv/MBq). Lung tissue exhibited low uptake of 18F-PEG6-IPQA due to the low affinity of this radiotracer to wild-type epidermal growth factor receptor kinase. The effective dose was 0.0165 mSv/MBq. No evidence of acute cardiotoxicity or of acute or delayed systemic toxicity was observed. On the basis of our estimates, diagnostic dosages of 18F-PEG6-IPQA up to 128 MBq (3.47 mCi) per injection should be safe for administration in the initial cohort of human patients in phase I clinical PET studies. Conclusion: The whole-body and individual organ radiation dosimetry characteristics and pharmacologic safety of diagnostic dosages of 18F-PEG6-IPQA in nonhuman primates indicate that this radiotracer should be acceptable for PET/CT studies in human patients.

Skeletal tumor burden on baseline 18F-fluoride PET/CT predicts bone marrow failure after 223Ra therapy

Purpose Determine if skeletal tumor burden on 18F-fluoride PET/CT (fluoride PET/CT) predicts the risk of bone marrow failure (BMF) after 223Ra dichloride therapy (223Ra). Methods Forty-one metastatic prostate cancer patients (43-89 years old; mean, 71 ± 9 years.) underwent fluoride PET/CT prior to 223Ra. Bone marrow failure was the primary end point and was defined as (1) development of hematologic toxicity (World Health Organization grade 3 or 4) associated with no recovery after 6 weeks or (2) death due to BMF after the last 223Ra dose. Bone marrow failure was correlated to fluoride PET/CT skeletal tumor burden (TLF10 [total lesion on fluoride PET/CT with SUVmax of 10 or greater]), use of chemotherapy, serum hemoglobin concentration, serum ALP, and serum prostate-specific antigen. Results The number of 223Ra cycles ranged from 2 to 6 (mean, 5). Of the 41 patients, 16 developed BMF (G3 = 12; G4 = 4). A significantly increased risk of developing BMF was observed in patients with TLF10 of 12,000 or greater (hazard ratio [HR], 11.09; P < 0.0001), hemoglobin of less than 10 g/dL (HR, 7.35; P = 0.0002), and AP > 146 UI/L (HR, 4.52; P = 0.0100). Neither concomitant (HR, 0.91; P = 0.88) nor subsequent use of chemotherapy (HR, 0.14; P = 0.84) increased the risk of BMF, nor was prostate-specific antigen greater than 10 &mgr;g/L (HR, 0.90; P = 0.86). Moreover, in a multivariable analysis, TLF10 was the only independent predictor of BMF (HR, 6.66; P = 0.0237). Conclusions 223Ra was beneficial and reduced the risk of death even in patients with a high skeletal tumor burden. Fluoride PET/CT is able to determine which patients will benefit from 223Ra and which will develop BMF.