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1.  Combined SPECT and Multidetector CT for Prostate Cancer Evaluations 
111In-capromab pendetide is an imaging probe for noninvasive detection of prostate cancer dissemination, and can be difficult to interpret because of low photon statistics resulting in noisy images with limited anatomical precision. We examined if a 16-slice multidetector computed tomography (MDCT) combined with single photon emission computed tomography (SPECT) could increase the impact on the clinical management and improve confidence in SPECT image interpretations in comparison to a relatively low-mA (limited resolution) CT. 17 scans were reviewed from a SPECT combined with low-mA CT scanner; 21 scans were reviewed from a SPECT combined with 16-slice MDCT scanner. Reports of the clinical interpretations from the imaging studies, additional examinations performed by referring physicians as a follow-up to the imaging results, and long-term clinical and laboratory follow-ups were used to define confidence of the SPECT/CT readings and impact of the readings on the patient management. The impact was defined as: the occurrence of the 111In-capromab pendetide interpretation resulted in additional imaging studies or biopsies. MDCT improved the quality and confidence in the characterization of small lymph nodes with or without uptake of 111In-capromab pendetide. The increased confidence with MDCT in SPECT/CT readings was evident in all cases reviewed in this study, and the impact on the clinical management was higher (8 out of 21) using SPECT/MDCT than the impact using SPECT combined with low-mA CT (2 out of 17). The dual-modality SPECT/CT provides a quantifiable benefit when MDCT is used instead of low-mA CT, particularly for prostate cancer evaluations using 111In-capromab pendetide.
PMCID: PMC3260786  PMID: 22267999
prostate cancer; capromab pendetide; SPECT/CT; MDCT; prostate specific membrane antigen (PSMA)
2.  Response, Survival and Toxicity after 131I-MIBG Therapy for Neuroblastoma in Pre-Adolescents, Adolescents and Adults 
Cancer  2011;117(18):4286-4293.
BACKGROUND
Adolescent and adult patients with neuroblastoma appear to have a more indolent disease course but a lower survival than their younger counterparts. The majority of neuroblastoma tumors specifically accumulate the radiolabeled norepinephrine analogue 131I-metaiodobenzylguanidine (MIBG). 131I-MIBG has therefore become increasingly used as targeted radiotherapy for relapsed or refractory neuroblastoma. The aim of this study was to characterize the toxicity and activity of this therapy in older patients.
METHODS
We performed a retrospective analysis of 39 consecutive patients ages 10 years and older with relapsed or refractory neuroblastoma who were treated with 131I-MIBG monotherapy at UCSF under Phase I, Phase II, and compassionate access protocols.
RESULTS
Sixteen patients were ≥18 years old at MIBG treatment initiation, whereas twenty-three were 10–17 years old. The median cumulative administered dose of 131I-MIBG was 17.8 mCi/kg. The majority of treatments led to grade 3 or 4 hematologic toxicities which were similar in frequency among age strata. Three patients subsequently developed hematologic malignancy or myelodysplasia. The overall rate of complete plus partial response was 46%. Patients ≥18 years old at time of first MIBG treatment had a significantly higher response rate compared to patients 10–17 years old (56% vs 39%, p=0.023). Median overall survival was 23 months with a trend toward longer overall survival for the ≥18 year old subgroup (p = 0.12).
CONCLUSIONS
Our findings suggest that 131I-MIBG is a highly effective salvage agent for adolescents and adults with neuroblastoma.
doi:10.1002/cncr.25987
PMCID: PMC3125487  PMID: 21387264
neuroblastoma; adult; adolescent; MIBG; radiopharmaceutical
3.  Lymphatic drainage mapping of prostate using filtered 99mTc-sulfur nanocolloid and SPECT/CT 
We have developed a practice procedure of prostate lymphoscintigraphy using SPECT/CT and filtered 99mTc-sulfur nanocolloid.
Methods
A total of 10 patients were enrolled for this study, and all administred with the 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 hours after the radiotracer administration directly into six locations of the prostate gland under a transrectal ultrasound guide. Radiation dose was estimated from the first 3 patients. The lymphatic drainage mapping and identification of lymph nodes were performed.
Results
Radiation dose estimates of filtered 99mTc-sulfur nanocollid from the first three patients were in the range of 3.9–5.2 mSv/MBq. Our results showed the locations of lymph nodes drainged from the prostate gland are similar to those found using 99mTc-Nanocoll.
Conclusion
Without the proprietary radiolabeled nanocolloid indicated for lymphoscintigraphy, prostate lymph node mapping and identification were feasible using filtered 99mTc-sulfur nanocolloid.
doi:10.2967/jnumed.110.085944
PMCID: PMC3129454  PMID: 21680690
prostate cancer; sulfur colloid; SPECT/CT; lymphatic mapping; sentinel node
4.  Thyroid and Hepatic Function After High Dose 131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Neuroblastoma 
Pediatric blood & cancer  2010;56(2):191-201.
Background
131I-Metaiodobenzylguanidine (131I-MIBG) provides targeted radiotherapy for children with neuroblastoma, a malignancy of the sympathetic nervous system. Dissociated radioactive iodide may concentrate in the thyroid, and MIBG is concentrated in the liver after MIBG therapy. The aim of our study was to analyze the effects of 131I-MIBG therapy on thyroid and liver function.
Procedure
Pre and post therapy thyroid and liver functions were reviewed in a total of 194 neuroblastoma patients treated with 131I-MIBG therapy. The cumulative incidence over time was estimated for both thyroid and liver toxicities. The relationship to cumulative dose/kg, number of treatments, time from treatment to follow-up, sex, and patient age was examined.
Results
In patients who presented with Grade 0 or Grade 1 thyroid toxicity at baseline, 12±4% experienced onset or worsening to Grade 2 hypothyroidism and one patient developed Grade 2 hyperthyroidism by two years after 131I-MIBG therapy. At two years post 131I-MIBG therapy, 76±4% patients experienced onset or worsening of hepatic toxicity to any grade, and 23±5% experienced onset of or worsening to Grade 3 or 4 liver toxicity. Liver toxicity usually was transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies.
Conclusion
The prophylactic regimen of potassium iodide and potassium perchlorate with 131I-MIBG therapy resulted in a low rate of significant hypothyroidism. Liver abnormalities following 131I-MIBG therapy were primarily reversible and did not result in late toxicity. 131I-MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction.
doi:10.1002/pbc.22767
PMCID: PMC3006009  PMID: 20830775
Neuroblastoma; 131I-MIBG; Hypothyroidism
5.  Combined SPECT and multidetector CT for prostate cancer evaluations 
111In-capromab pendetide is an imaging probe for noninvasive detection of prostate cancer dissemination, and can be difficult to interpret because of low photon statistics resulting in noisy images with limited anatomical precision. We examined if a 16-slice multidetector computed tomography (MDCT) combined with single photon emission computed tomography (SPECT) could increase the impact on the clinical management and improve confidence in SPECT image interpretations in comparison to a relatively low-mA (limited resolution) CT. 17 scans were reviewed from a SPECT combined with low-mA CT scanner; 21 scans were reviewed from a SPECT combined with 16-slice MDCT scanner. Reports of the clinical interpretations from the imaging studies, additional examinations performed by referring physicians as a follow-up to the imaging results, and long-term clinical and laboratory follow-ups were used to define confidence of the SPECT/CT readings and impact of the readings on the patient management. The impact was defined as: the occurrence of the 111In-capromab pendetide interpretation resulted in additional imaging studies or biopsies. MDCT improved the quality and confidence in the characterization of small lymph nodes with or without uptake of 111In-capromab pendetide. The increased confidence with MDCT in SPECT/CT readings was evident in all cases reviewed in this study, and the impact on the clinical management was higher (8 out of 21) using SPECT/MDCT than the impact using SPECT combined with low-mA CT (2 out of 17). The dual-modality SPECT/CT provides a quantifiable benefit when MDCT is used instead of low-mA CT, particularly for prostate cancer evaluations using 111In-capromab pendetide.
PMCID: PMC3260786  PMID: 22267999
Prostate cancer; capromab pendetide; SPECT/CT; MDCT; prostate specific membrane antigen (PSMA)
6.  In vivo Tumor Grading of Prostate Cancer using Quantitative 111In-Capromab Pendetide SPECT/CT 
We have developed an in vivo antibody uptake quantification method using 111In-capromab pendetide single photon emission computed tomography combined with computed tomography (SPECT/CT) technology. Our goal is to evaluate this noninvasive antibody quantification method for potential prostate tumor grading.
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 uniform phantom filled with 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 (PSF), and the PSF was implemented in a deconvolution-based partial volume error (PVE) correction algorithm. The recovery capability to correctly estimate true tracer concentration values was tested using prostate-like and bladder-like lesion phantoms fitted in the modified NEMA/IEC 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 VA Medical Center. The CT portion of SPECT/CT was used for CT-based attenuation map generation as well as an anatomical 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 prostate gland with cylindrical volumes of interest (VOIs) having dimensions of 1.5 cm both in diameter and height.
Results
Reconstructed SPECT images further corrected by the deconvolution-based PVE correction could recover true tracer concentrations in volumes as small as 7.77 ml up to 90% in phantom measurements. 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 noninvasive prostate tumor grading potential using quantitative 111In-capromab pendetide SPECT/CT for prostate cancer evaluation.
doi:10.2967/jnumed.109.067108
PMCID: PMC2821016  PMID: 20008977
prostate cancer; capromab pendetide; SPECT; SPECT/CT; quantification; tracer quantification; quantitative SPECT; prostate specific membrane antigen (PSMA)
7.  Comparison of Iodine-123 Metaiodobenzylguanidine (MIBG) Scan and [18F]Fluorodeoxyglucose Positron Emission Tomography to Evaluate Response After Iodine-131 MIBG Therapy for Relapsed Neuroblastoma 
Journal of Clinical Oncology  2009;27(32):5343-5349.
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 [18F]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 (131I) MIBG (NANT-2000-01) were eligible for inclusion if they had concomitant FDG-PET and MIBG scans. 131I-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.
doi:10.1200/JCO.2008.20.5732
PMCID: PMC2773221  PMID: 19805691
8.  Phase II Study of High-Dose [131I]Metaiodobenzylguanidine Therapy for Patients With Metastatic Pheochromocytoma and Paraganglioma 
Journal of Clinical Oncology  2009;27(25):4162-4168.
Purpose
To evaluate the safety and efficacy of high-dose [131I]metaiodobenzylguanidine ([131I]MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL).
Methods
Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [131I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [131I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [131I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [131I]MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [123I]MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A.
Results
The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4).
Conclusion
Although serious toxicity may occur, the survival and response rates achieved with high-dose [131I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.
doi:10.1200/JCO.2008.21.3496
PMCID: PMC2734428  PMID: 19636009
9.  Phase I Trial of Oral Irinotecan and Temozolomide for Children With Relapsed High-Risk Neuroblastoma: A New Approach to Neuroblastoma Therapy Consortium Study 
Journal of Clinical Oncology  2009;27(8):1290-1296.
Purpose
Irinotecan and temozolomide have single-agent activity and schedule-dependent synergy against neuroblastoma. Because protracted administration of intravenous irinotecan is costly and inconvenient, we sought to determine the maximum-tolerated dose (MTD) of oral irinotecan combined with temozolomide in children with recurrent/resistant high-risk neuroblastoma.
Patients and Methods
Patients received oral temozolomide on days 1 through 5 combined with oral irinotecan on days 1 through 5 and 8 through 12 in 3-week courses. Daily oral cefixime was used to reduce irinotecan-associated diarrhea.
Results
Fourteen assessable patients received 75 courses. Because neutropenia and thrombocytopenia were initially dose-limiting, temozolomide was reduced from 100 to 75 mg/m2/d for subsequent patients. Irinotecan was then escalated from 30 to 60 mg/m2/d. First-course grade 3 diarrhea was dose-limiting in one of six patients treated at the irinotecan MTD of 60 mg/m2/d. Other toxicities were mild and reversible. The median SN-38 lactone area under the plasma concentration versus time curve at this dose was 72 ng · hr/mL. One patient with bulky soft tissue disease had a complete response through six courses. Six additional patients received a median of seven courses (range, three to 22 courses) before progression.
Conclusion
This all-oral regimen was feasible and well tolerated in heavily pretreated children with resistant neuroblastoma, and seven (50%) of 14 assessable patients had response or disease stabilization for three or more courses in this phase I trial. SN-38 lactone exposures were similar to those reported with protracted intravenous irinotecan. The dosages recommended for further study in this patient population are temozolomide 75 mg/m2/d plus irinotecan 60 mg/m2/d when given with cefixime.
doi:10.1200/JCO.2008.18.5918
PMCID: PMC2667827  PMID: 19171709
10.  Iodine-131—Metaiodobenzylguanidine Double Infusion With Autologous Stem-Cell Rescue for Neuroblastoma: A New Approaches to Neuroblastoma Therapy Phase I Study 
Journal of Clinical Oncology  2009;27(7):1020-1025.
Purpose
Iodine-131—metaiodobenzylguanidine (131I-MIBG) provides targeted radiotherapy with more than 30% response rate in refractory neuroblastoma, but activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum-tolerated dose of 131I-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem-cell rescue (ASCR) 2 weeks after the second dose.
Patients and Methods
The 131I-MIBG dose was escalated using a 3 + 3 phase I trial design, with levels calculated by cumulative red marrow radiation index (RMI) from both infusions. Using dosimetry, the second infusion was adjusted to achieve the target RMI, except at level 4, where the second infusion was capped at 21 mCi/kg.
Results
Twenty-one patients were enrolled onto the study at levels 1 to 4, with 18 patients assessable for toxicity and 20 patients assessable for response. Cumulative 131I-MIBG given to achieve the target RMI ranged from 22 to 50 mCi/kg, with cumulative RMI of 3.2 to 8.92 Gy. No patient had a dose-limiting toxicity. Reversible grade 3 nonhematologic toxicity occurred in six patients at level 4, establishing the recommended cumulative dose as 36 mCi/kg. The median time to absolute neutrophil count more than 500/μL after ASCR was 13 days (4 to 27 days) and to platelet independence was 17 days (6 to 47 days). Responses included two partial responses, eight mixed responses, three stable disease, and seven progressive disease. Responses by semiquantitative MIBG score occurred in eight patients, soft tissue responses occurred in five of 11 patients, but bone marrow responses occurred in only two of 13 patients.
Conclusion
The lack of toxicity with this approach allowed dramatic dose intensification of 131I-MIBG, with minimal toxicity and promising activity.
doi:10.1200/JCO.2007.15.7628
PMCID: PMC2738616  PMID: 19171714
11.  Presurgical Multimodality Neuroimaging in Electroencephalographic Lateralized Temporal Lobe Epilepsy 
Annals of neurology  1997;42(6):829-837.
The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.
doi:10.1002/ana.410420603
PMCID: PMC2709486  PMID: 9403474
12.  Design and Applications of a Multimodality Image Data Warehouse Framework 
A comprehensive data warehouse framework is needed, which encompasses imaging and non-imaging information in supporting disease management and research. The authors propose such a framework, describe general design principles and system architecture, and illustrate a multimodality neuroimaging data warehouse system implemented for clinical epilepsy research. The data warehouse system is built on top of a picture archiving and communication system (PACS) environment and applies an iterative object-oriented analysis and design (OOAD) approach and recognized data interface and design standards. The implementation is based on a Java CORBA (Common Object Request Broker Architecture) and Web-based architecture that separates the graphical user interface presentation, data warehouse business services, data staging area, and backend source systems into distinct software layers. To illustrate the practicality of the data warehouse system, the authors describe two distinct biomedical applications—namely, clinical diagnostic workup of multimodality neuroimaging cases and research data analysis and decision threshold on seizure foci lateralization. The image data warehouse framework can be modified and generalized for new application domains.
doi:10.1197/jamia.M0988
PMCID: PMC344584  PMID: 11971885

Results 1-12 (12)