Carina Mari Aparici

Comparison of Iodine-123 Metaiodobenzylguanidine (MIBG) Scan and [18F]Fluorodeoxyglucose Positron Emission Tomography to Evaluate Response After Iodine-131 MIBG Therapy for Relapsed Neuroblastoma

PURPOSE Children with relapsed neuroblastoma have poor survival. It is crucial to have a reliable method for evaluating functional response to new therapies. In this study, we compared two functional imaging modalities for neuroblastoma: metaiodobenzylguanidine (MIBG) scan for uptake by the norepinephrine transporter and [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake for glucose metabolic activity. PATIENTS AND METHODS Patients enrolled onto a phase I study of sequential infusion of iodine-131 ((131)I) MIBG (NANT-2000-01) were eligible for inclusion if they had concomitant FDG-PET and MIBG scans. (131)I-MIBG therapy was administered on days 0 and 14. For each patient, we compared all lesions identified on concomitant FDG-PET and MIBG scans and gave scans a semiquantitative score. RESULTS The overall concordance of positive lesions on concomitant MIBG and FDG-PET scans was 39.6% when examining the 139 unique anatomic lesions. MIBG imaging was significantly more sensitive than FDG-PET overall and for the detection of bone lesions (P < .001). There was a trend for increased sensitivity of FDG-PET for detection of soft tissue lesions. Both modalities showed similar improvement in number of lesions identified from day 0 to day 56 scan and in semiquantitative scores that correlated with overall response. FDG-PET scans became completely negative more often than MIBG scans after treatment. CONCLUSION MIBG scan is significantly more sensitive for individual lesion detection in relapsed neuroblastoma than FDG-PET, though FDG-PET can sometimes play a complementary role, particularly in soft tissue lesions. Complete response by FDG-PET metabolic evaluation did not always correlate with complete response by MIBG uptake.

In Vivo Tumor Grading of Prostate Cancer Using Quantitative 111In-Capromab Pendetide SPECT/CT

We have developed an in vivo method to quantify antibody uptake using 111In-capromab pendetide SPECT combined with CT (SPECT/CT). Our goal was to evaluate this method for potential grading of prostate tumors. Methods: Our phantom experiments focused on the robustness of an advanced iterative reconstruction algorithm that involves corrections for photon attenuation, scatter, and geometric blurring caused by radionuclide collimators. The conversion factors between image values and tracer concentrations (in Bq/mL) were calculated from a uniform phantom filled with an aqueous solution of 111InCl3 using the same acquisition protocol and reconstruction parameters as for patient studies. In addition, the spatial resolution of the reconstructed images was measured from a point source phantom. The measured spatial resolution was modeled into a point-spread function, and the point-spread function was implemented in a deconvolution-based partial-volume-error correction algorithm. The recovery capability to correctly estimate true tracer concentrations was tested using prostatelike and bladderlike lesion phantoms fitted in the modified National Electrical Manufacturers Association/International Electrotechnical Commission body phantom. Patients with biopsy-proven prostate cancer (n = 10) who underwent prostatectomy were prospectively enrolled in the preoperative SPECT/CT studies at the San Francisco Veterans Affairs Medical Center. The CT portion of SPECT/CT was used to generate CT-based attenuation maps and as an anatomic localization tool for clinical interpretation. Pathologic Gleason grades were compared with in vivo antibody uptake value (AUV) normalized by injected dose, effective half-life, and injection-scan time difference. AUVs were calculated in each lobe of the prostate gland with cylindric volumes of interest having dimensions of 1.5 cm in both diameter and height. Results: Reconstructed SPECT images further corrected by the deconvolution-based partial-volume-error correction could recover tracer concentrations up to 90% of true values in measurements of phantom volumes as small as 7.77 mL. From patient studies, there was a statistically significant correlation (ρ = 0.71, P = 0.033) between higher AUVs (from either left or right lobe) and higher components of pathologic Gleason scores. Conclusion: Our results strongly indicate potential for noninvasive prostate tumor grading using quantitative 111In-capromab pendetide SPECT/CT.

Functional Imaging for Prostate Cancer: Therapeutic Implications

Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities computed tomography (CT) or magnetic resonance imaging (single photon emission computed tomography [SPECT]/CT, positron emission tomography [PET]/CT, and PET/magnetic resonance imaging), are promising tools for the management of prostate cancer, particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regard to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, although the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging, including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects.

Mapping of Lymphatic Drainage from the Prostate Using Filtered 99mTc-Sulfur Nanocolloid and SPECT/CT

We have developed a practice procedure for prostate lymphoscintigraphy using SPECT/CT and filtered 99mTc-sulfur nanocolloid, as an alternative to the proprietary product 99mTc-Nanocoll, which is not approved in the United States. Methods: Ten patients were enrolled for this study, and all received radiotracer prepared using a 100-nm membrane filter at a commercial radiopharmacy. Whole-body scans and SPECT/CT studies were performed within 1.5–3 h after the radiotracer had been administered directly into 6 locations of the prostate gland under transrectal ultrasound guidance. The radiation dose was estimated from the first 3 patients. Lymphatic drainage mapping was performed, and lymph nodes were identified. Results: The estimated radiation dose ranged from 3.9 to 5.2 mSv/MBq. The locations of lymph nodes draining the prostate gland were similar to those found using the proprietary product. Conclusion: When the proprietary radiolabeled nanocolloid indicated for lymphoscintigraphy is not available, prostate lymph node mapping and identification are still feasible using filtered 99mTc-sulfur nanocolloid.

Frequency and clinical implications of incidental new primary cancers detected on true whole-body 18F-FDG PET/CT studies.

Objective To determine the frequency of additional primary malignancies in patients undergoing staging/restaging with PET/computed tomography (CT) and to determine the frequency with which these unsuspected findings change clinical management. Methods This is a retrospective review of 556 patients who had undergone a total of 804 PET/CTs for staging/restaging. Lesions that were at an atypical location for a metastasis from the primary malignancy (indication for the study) and had a maximum standardized uptake value greater than 2.5 were considered suspicious. Suspicious lesions were followed up by a combination of clinical examination, biopsy, and additional and/or follow-up imaging. Results Forty-three (7.7%) patients had lesions that were suspicious for a newly discovered primary malignancy that was different from the known/suspected malignancy (indication for study). Eight (1.4% of 556) of these patients had biopsy confirmation of an additional synchronous or metachronous primary malignancy. However, these suspicious lesions changed the clinical management for 18 (3.2% of 556) patients. Patients with early-stage disease (stages 1 and 2) based on the malignancy for which the study was conducted were three times more likely to have these suspicious lesions biopsied, evaluated by clinical examination or by additional immediate imaging than were patients with advanced-stage disease (stages 3 and 4); however, this difference was not statistically significant (P=0.08). Conclusion Unsuspected additional primary malignancies are rarely identified in patients undergoing staging/restaging with PET/CT but have the potential to significantly impact clinical management.

Investigation of dynamic SPECT measurements of the arterial input function in human subjects using simulation, phantom and human studies

Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic (94)Tc-methoxyisobutylisonitrile ((94)Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K(1) for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K(1). For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from (94)Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of (99m)Tc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The spatiotemporal maximum-likelihood expectation-maximization (4D ML-EM) reconstructions gave more accurate reconstructions than did standard frame-by-frame static 3D ML-EM reconstructions. The SPECT/P results showed that 4D ML-EM reconstruction gave higher and more accurate estimates of K(1) than did 3D ML-EM, yielding anywhere from a 44% underestimation to 24% overestimation for the three patients. The SPECT/D results showed that 4D ML-EM reconstruction gave an overestimation of 28% and 3D ML-EM gave an underestimation of 1% for K(1). For the patient study the 4D ML-EM reconstruction provided continuous images as a function of time of the concentration in both ventricular cavities and myocardium during the 2 min infusion. It is demonstrated that a 2 min infusion with a two-headed SPECT system rotating 180° every 54 s can produce measurements of blood pool and myocardial TACs, though the SPECT simulation studies showed that one must sample at least every 30 s to capture a 1 min infusion input function.

Focal Colonic FDG Activity with PET/CT: Guidelines for Recommendation of Colonoscopy.

Focal 18 F-fluorodeoxyglucose (FDG) colonic activity can be incidentally seen in positron emission tomography/computed tomography (PET/CT) scans. Its clinical significance is still unclear. The purpose of this study was to assess the significance of focal FDG activity in PET/CT scans by correlating the imaging findings to colonoscopy results, and come up with some guidelines for recommendation of follow-up colonoscopy. A total of 133 patients who underwent both 18 F-FDG PET/CT for different oncological indications and colonoscopy within 3 months were retrospectively studied. Imaging, colonoscopy and pathology results were analyzed. Of the 133 FDG-PET/CT scans, 109/133 (82%) did not show focal colonic FDG activity, and 24/133 (18%) did. Of the 109/133 PET/CTs without focal colonic FDG activity, 109/109 (100%) did not have evidence of colon cancer after colonoscopy and histology. Of the 24/133 PET/CTs with focal colonic FDG activity, 10/24 (42%) had pathologic confirmation of colon cancer and 14/24 (58%) did not have evidence of colon cancer after colonoscopy and histological analysis. Sensitivity was 10/10 (100%), specificity 109/123 (89%), positive predictive value (PPV) 10/24 (42%) and negative predictive value (NPV) 109/109 (100%). Incidental focal 18 FDG activity in PET/CT imaging shows a high sensitivity, specificity and NPV for malignancy, with a not so high PPV of 42%. Although some people would argue that a 42% chance of malignancy justifies colonoscopy, this maybe is not possible in all cases. However, the high sensitivity of the test does not allow these studies to be overlooked. We provide our recommendations as per when to send patients with focal FDG colonic activity to have further characterization with colonoscopy.

Normal SUV values measured from NaF18- PET/CT bone scan studies.

Objectives Cancer and metabolic bone diseases can alter the SUV. SUV values have never been measured from healthy skeletons in NaF18-PET/CT bone scans. The primary aim of this study was to measure the SUV values from normal skeletons in NaF18-PET/CT bone scans. Methods A retrospective study was carried out involving NaF18- PET/CT bone scans that were done at our institution between January 2010 to May 2012. Our excluding criteria was patients with abnormal real function and patients with past history of cancer and metabolic bone diseases including but not limited to osteoporosis, osteopenia and Paget’s disease. Eleven studies met all the criteria. Results The average normal SUVmax values from 11 patients were: cervical vertebrae 6.84 (range 4.38–8.64), thoracic vertebrae 7.36 (range 6.99–7.66), lumbar vertebrae 7.27 (range 7.04–7.72), femoral head 2.22 (range 1.1–4.3), humeral head 1.82 (range 1.2–2.9), mid sternum 5.51 (range 2.6–8.1), parietal bone 1.71 (range 1.3–2.4). Conclusion According to our study, various skeletal sites have different normal SUV values. SUV values can be different between the normal bones and bones with tumor or metabolic bone disease. SUV can be used to quantify NaF-18 PET/CT studies. If the SUV values of the normal skeleton are known, they can be used in the characterization of bone lesions and in the assessment of treatment response to bone diseases.

Validation of FDG Uptake in the Arterial Wall as an Imaging Biomarker of Atherosclerotic Plaques with 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG-PET/CT)

From the literature, the prevalence of fluorodeoxyglucose (FDG) uptake in large artery atherosclerotic plaques shows great heterogeneity. We retrospectively reviewed 100 consecutive patients who underwent FDG‐positron emission tomography‐computed tomography (PET/CT) imaging of their whole body, to evaluate FDG uptake in the arterial wall.

Factors Affecting Uptake of NaF-18 by the Normal Skeleton

Background The primary aim of this study was to examine if factors such as renal function, height, weight and age could affect the uptake of sodium fluoride-18 (NaF-18) by the normal bone. This is the first study to examine the possible factors that can influence NaF-18 uptake in the normal bone. Methods A retrospective study was done on NaF-18 PET/CT bone scans from January 2010 to May 2012 at our institution. All NaF-18 PET/CT studies used the same clinical protocol. Our excluding criteria were patients with abnormal renal function and patients with past history of cancer and metabolic bone diseases. Spearman’s correlation was used to analyze the data. Results From our study (n = 11 patients), no correlation was found between SUVmax and serum creatinine and between SUVmax and age. However, significant correlations were found between SUVmax and height (cm) and between SUVmax and weight (kg) for thoracic 5, 7, 12 and lumbar 2 vertebral levels. Conclusion Based on our findings, SUVmax values in NaF-18 PET/CT bone scans can vary depending on the patient’s height, weight and bone region. This information can be helpful in diagnosing and monitoring bone pathologies and can help explain the clinical findings.