David Bushnell

Standard Imaging Techniques for Neuroendocrine Tumors

Several diagnostic imaging techniques have been used successfully for evaluating patients with neuroendocrine tumors (NETs). These techniques include computed tomography (CT), magnetic resonance imaging, positron emission tomography/CT, single-photon emission CT (SPECT), and SPECT/CT. This article reviews the various imaging methods and their respective advantages and limitations for use in different types of NETs, in particular carcinoid tumors.

Feasibility and advantage of adding 131 I-MIBG to 90 Y-DOTATOC for treatment of patients with advanced stage neuroendocrine tumors

BackgroundPeptide receptor radionuclide therapy (PRRT) is an effective form of treatment for patients with metastatic neuroendocrine tumors (NETs). However, delivering sufficient radiation dose to the tumor to result in a high percentage of long-term tumor remissions remains challenging because of the limits imposed on administered activity levels by radiation damage to normal tissues. The goal of this study was to evaluate the dosimetric advantages of adding 131I meta-iodobenzylguanidine (131I-MIBG) to 90Y DOTA Phe1-Tyr3-octreotide (90Y-DOTATOC) in patients with advanced stage midgut NETs.MethodsTen patients were imaged simultaneously with 131I-MIBG and 111In-pentetreotide (as a surrogate for 90Y-DOTATOC) on days 1, 2, and 3 post-administration. Blood samples were obtained at the same time points. Using dosimetry measures from this data and our previously published methodology for calculating optimal combined administered activity levels for therapy, we determined the amount of 131I-MIBG that could be added to 90Y-DOTATOC without exceeding normal organ dose limits (marrow and kidneys) along with the expected increase in associated tumor dose, if any.ResultsWe found that a median value of 34.6 GBq of 131I-MIBG could be safely added to 90Y-DOTATOC (delivered over multiple cycles) by reducing the maximum total deliverable 90Y-DOTATOC by a median value of 24.5%. Taking this treatment approach, we found that there would be a median increase in deliverable tumor dose of 4,046 cGy in six of the ten subjects. Of note, there were a small number of metastases that were positive for only one or the other of these radiopharmaceuticals within the same subject.ConclusionsWe conclude that approximately half of the patients with midgut NETs that are eligible for PRRT could reasonably be expected to benefit from the addition of 131I-MIBG to 90Y-DOTATOC.

Localization of Unknown Primary Site with 68Ga-DOTATOC PET/CT in Patients with Metastatic Neuroendocrine Tumor

Localization of the site of the unknown primary tumor is critical for surgical treatment of patients presenting with neuroendocrine tumor (NET) with metastases. Methods: Forty patients with metastatic NET and unknown primary site underwent 68Ga-DOTATOC PET/CT in a single-site prospective study. The 68Ga-DOTATOC PET/CT was considered true-positive if the positive primary site was confirmed by histology or follow-up imaging. The scan was considered false-positive if no primary lesion was found corresponding to the 68Ga-DOTATOC–positive site. All negative scans for primary tumor were considered false-negative. A scan was classified unconfirmed if 68Ga-DOTATOC PET/CT suggested a primary, however, no histology was obtained and imaging follow-up was not confirmatory. Results: The true-positive, false-positive, false-negative, and unconfirmed rates for unknown primary tumor were 38%, 7%, 50%, and 5%, respectively. Conclusion: 68Ga-DOTATOC PET/CT is an effective modality in the localization of unknown primary in patients with metastatic NET.

Detectability of simulated brain activation using dual radioisotope SPECT based on size and intensity of the focal hyperactivity

RATIONALE AND OBJECTIVESnSimultaneous single-photon emission computed tomography (SPECT) neuroimaging with both technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and iodine-123 (123I) N-isopropyl-iodoamphetamine is a recently introduced method with potential for assessing activation phenomena in the brain. However, there is limited information on the accuracy of the technique for detecting focal cortical sites of neuroactivation. We determined, in vitro, what levels of activation could be detected as a function of the size of the activated region.nnnMETHODSnA Lucite brain phantom was filled with both 123I and 99mTc so as to simulate both a nonactivated state (123I) along with focal sites of activation (99mTc). Simulated activations ranged from 0 to 18% in volumes of 7, 14, 20, and 27 cm3. Imaging was performed with a triple-detector gamma camera using a 10% symmetric window at 140 keV and 10% asymmetric window around 159 keV. No correction was made for gamma cross-talk. To determine whether a simulated activation was detected, the 99mTc: 123I count ratios in the activated regions were compared by t test with ratios in nonactivated regions of similar volume. Detection sensitivities also were calculated as the fraction of the activated 99mTc: 123I ratios that were greater than the mean + 2 standard deviations of the corresponding nonactivated ratios.nnnRESULTSnAll sites of simulated activations of 10% or greater were detected. The detection sensitivity was 100% (95% confidence interval, 90-100%) for the two largest chambers with simulated activations of 13-18%. Activations in the 3-6% range, in the same-sized chambers, were detected with a limited sensitivity (67% with a confidence interval of 45-84%). In the 14-cm3 chamber, simulated activations in the 13-18% range were detected with 90% sensitivity (confidence interval, 74-98%). In general, the detection sensitivity was greater for larger chambers and higher levels of simulated activation.nnnCONCLUSIONnWe conclude that the dual-radioisotope technique using triple-detector SPECT systems and low-energy all-purpose (LEAP) collimators should be highly reliable for identifying focal brain activations above 13% that cover at least 14 cm3 of brain cortex. Smaller, less intense sites of activation will be detected with reduced frequency. These conclusions are based on our assessment of only the physical parameters involved in this methodology and other factors (e.g., the possibility that the relation between cerebral radiotracer concentration and regional cerebral blood flow) may affect the results obtained with patients.