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Unlabelled: Current standard practice for radioembolization treatment planning makes use of nuclear medicine imaging (NMI) of (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) arterial distributions for the assessment of lung shunting and extrahepatic uptake. Our aim was to retrospectively compare NMI with mapping angiography in the detection and localization of extrahepatic (99m)Tc-MAA and to evaluate the typical and atypical findings of NMI in association with catheter placement., Methods: One hundred seventy-four patients underwent diagnostic angiography in preparation for radioembolization. (99m)Tc-MAA was administered to the liver via a microcatheter positioned in the desired hepatic artery. Planar scintigraphy imaging followed by SPECT/CT imaging was obtained within 2 h. All images were reviewed for hepatic and extrahepatic (99m)Tc-MAA deposition and compared with the mapping angiogram., Results: Intrahepatic lobe shunting was present on NMI in only 2.9% of the cases but was present in 62.5% of the patients with portal vein thrombosis. Extrahepatic distributions included lungs (100%), the gallbladder (49%) if present, and locations involving hepaticoenteric arterial anatomy recognized on angiograms (16%). Free pertechnetate was identified on 38% of the nuclear medicine images. Three percent of nuclear medicine images showed alternative findings such as a thyroid nodule or metallic artifact., Conclusion: Patients being considered for radioembolization should undergo both angiography and scintigraphy for the assessment of hepaticoenteric arterial anatomy, hepatopulmonary shunting, and appropriate dosimetry considerations. Knowledge of the expected distribution of (99m)Tc-MAA with normal variants and potential nontarget delivery to adjacent structures is critical in improving clinical outcomes., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Preclinical studies suggest that bortezomib, through inhibition of nuclear factor-κB (NF-κB) activation, may enhance the effects of radioimmunotherapy. This phase I trial was designed to determine the maximum tolerated dose (MTD) of weekly bortezomib induction combined with Y-90-ibritumomab tiuxetan followed at the time of count recovery by weekly bortezomib consolidation in patients with relapsed/refractory follicular or transformed non-Hodgkin lymphoma. Grade 3 or 4 toxicities were observed in eight of nine treated patients, and all but one of these toxicities were hematologic. One patient had grade 3 cardiotoxicity. A dose limiting toxicity (DLT) of grade 4 thrombocytopenia was observed in two of three patients treated with bortezomib at 1.6 mg/m(2), resulting in a MTD of 1.3 mg/m(2). The overall response rate was 89% (two complete response [CR], six partial response [PR], one stable disease [SD]), with a median progression-free survival of 6.5 months (range: 3-22.5+ months). A phase II trial at the MTD is under way to better define the toxicity and effectiveness of this regimen.

Unlabelled: Radioembolization with 90Y microspheres represents a novel transarterial radiation treatment for liver tumors. The purpose of this pilot study was to evaluate the findings of postimplantation PET/CT of 90Y glass microspheres., Methods: Three patients with hepatocellular carcinoma and 2 patients with liver metastases (1 neuroendocrine, 1 colorectal) underwent PET/CT after radioembolization. Four patients underwent imaging at 1 mo to assess response and confirm PET/CT findings; 1 patient underwent PET/CT at 4 d after 90Y implantation. Patients were followed for adverse events., Results: Standard PET/CT enabled the localization of 90Y glass microspheres for all patients. None of the patients experienced adverse events related to nontarget deposition., Conclusion: Standard PET/CT may be used to assess the localization of 90Y glass microspheres. This approach provides a simple, rapid, and universally applicable method of confirming microsphere deposition. With further validation, this technique may potentially become the standard of care for confirming microsphere distribution.

Purpose: This study prospectively evaluated the use of lymphangiogram, computed tomography/magnetic resonance imaging, and positron emission tomography (PET) imaging of lymph node metastasis in patients receiving definitive chemoradiotherapy for cervical cancer., Materials and Methods: Twenty patients underwent lymphangiogram, computed tomography/magnetic resonance imaging, and PET. There was no histologic verification of metastasis. Four lymph node regions, including the internal, external, and common iliacs, and para-aortic, were scored as positive or negative for metastasis. Agreement between imaging was analyzed using multirater kappa and disease-free survival utilizing Kaplan Meier survival curves and log-rank test., Results: Agreement between imaging was most consistent in the common iliacs (P < 0.001) and least in the para-aortic region (P = 0.41). Disease-free survival (DFS) at one year was statistically associated with positive PET imaging (25%) versus negative PET imaging (86%) (P = 0.033) in the common iliac lymph node region. No other single lymph node region in any modality was statistically associated with DFS. One-year DFS in patients with any positive areas on PET imaging was 50% compared with 90% in patients with negative PET imaging (P = 0.02). Seven patients were noted to have no metastasis in any region by all 3 of the imaging modalities; the 1-year DFS in these 7 patients was 100% compared with 59% in the 13 patients with any positive nodal area (P = 0.05)., Conclusions: Positive lymphadenopathy on PET imaging was associated with reduced DFS.

Purpose: Therapeutic strategies to enhance the efficacy of radioimmunotherapy have not been explored. Motexafin gadolinium is a novel anticancer agent that targets redox-dependent pathways and enhances sensitivity of tumor cells to ionizing radiation., Experimental Design: We did preclinical studies examining motexafin gadolinium combined with rituximab and/or radiation in lymphoma cells. We subsequently completed a phase I clinical trial combining escalating doses of motexafin gadolinium concurrently with standard [(90)Y]ibritumomab tiuxetan for patients with relapsed/refractory non-Hodgkin's lymphoma., Results: In HF1 lymphoma cells, motexafin gadolinium and rituximab resulted in synergistic cytotoxicity (combination index, 0.757) through a mitochondrial-mediated caspase-dependent pathway, whereas cell death in Ramos and SUDHL4 cells was additive. Motexafin gadolinium/rituximab combined with radiation (1-3 Gy) resulted in additive apoptosis. Twenty-eight of 30 patients were evaluable on the phase I clinical trial. Median age was 65 years (47-87 years), and histologies were marginal-zone (n = 1), mantle-cell (n = 3), diffuse large cell (n = 6), and follicular lymphoma (n = 18). Of all patients, 86% were rituximab refractory. Therapy was well tolerated, and no dose-limiting toxicity was seen. Overall response rate was 57% [complete remission (CR), 43%], with median time-to-treatment failure of 10 months (1-48+ months) and median duration-of-response of 17 months. Of note, all responses were documented at 4 weeks. Furthermore, in rituximab-refractory follicular lymphoma (n = 14), overall response rate was 86% (CR, 64%), with a median time-to-treatment failure of 14 months (2-48+ months)., Conclusions: This represents the first report of a novel agent to be combined safely concurrently with radioimmunotherapy. Furthermore, tumor responses with [(90)Y]ibritumomab tiuxetan/motexafin gadolinium were prompt with a high rate of CRs, especially in rituximab-refractory follicular lymphoma.

Purpose: To correlate changes in 2-deoxy-2-[18F]fluoro-d-glucose (18-FDG) positron emission tomography (PET) (18-FDG-PET) uptake with response and disease-free survival with combined modality neoadjuvant therapy in patients with locally advanced rectal cancer., Methods and Materials: Charts were reviewed for consecutive patients with ultrasound-staged T3x to T4Nx or TxN1 rectal adenocarcinoma who underwent preoperative chemoradiation therapy at Fox Chase Cancer Center (FCCC) or Robert H. Lurie Comprehensive Cancer Center of Northwestern University with 18-FDG-PET scanning before and after combined-modality neoadjuvant chemoradiation therapy . The maximum standardized uptake value (SUV) was measured from the tumor before and 3 to 4 weeks after completion of chemoradiation therapy preoperatively. Logistic regression was used to analyze the association of pretreatment SUV, posttreatment SUV, and % SUV decrease on pathologic complete response (pCR), and a Cox model was fitted to analyze disease-free survival., Results: A total of 53 patients (FCCC, n = 41, RLCCC, n = 12) underwent pre- and postchemoradiation PET scanning between September 2000 and June 2006. The pCR rate was 31%. Univariate analysis revealed that % SUV decrease showed a marginally trend in predicting pCR (p = 0.08). In the multivariable analysis, posttreatment SUV was shown a predictor of pCR (p = 0.07), but the test results did not reach statistical significance. None of the investigated variables were predictive of disease-free survival., Conclusions: A trend was observed for % SUV decrease and posttreatment SUV predicting pCR in patients with rectal cancer treated with preoperative chemoradiation therapy. Further prospective study with a larger sample size is warranted to better characterize the role of 18-FDG-PET for response prediction in patients with rectal cancer.

Purpose: To determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 ((90)Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation., Patients and Methods: Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma (NHL). Individualized (90)Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of (90)Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation., Results: Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively., Conclusion: Dose-escalated (90)Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.

Objective: To examine the relationship of baseline homocysteine levels with bone mineral density (BMD) and incidence of fractures over 2 years in women with and without systemic lupus erythematosus (SLE)., Methods: Women with SLE (n = 100) and without SLE (n = 100) were matched according to age (+/- 5 yrs), race, and menopausal status. Data were collected from 1997 to 2004, including hip, lumbar spine (L-spine), and distal forearm BMD, serum homocysteine levels, and a self-administered questionnaire on osteoporosis risk factors, medications and symptomatic fractures at baseline and 2-year followup. Analyses were performed to compare homocysteine levels, BMD, and incident fractures and to evaluate the relationship of homocysteine with BMD and incident fractures in both groups., Results: Mean homocysteine +/- SD was higher (p < 0.001) in women with SLE (9.88 +/- 3.8 micromol/l) than in women without SLE (7.98 +/- 2.6 micromol/l). Women with SLE had significantly lower L-spine BMD Z-scores, while hip BMD Z-scores and distal forearm BMD T-scores were nonsignificantly lower than in women without SLE. No significant correlations were observed between homocysteine and BMD in either group. Thirteen women with SLE experienced new fractures, while 4 women without SLE had new fractures over 2 years (p = 0.035); however, there was no association between homocysteine levels and incident fractures in either group., Conclusion: Women with SLE had significantly greater baseline homocysteine, lower L-spine BMD, and more new fractures over 2 years, compared with women without SLE. Homocysteine levels were not significantly associated with BMD and did not predict new fractures in women with or without SLE over 2 years.

Somatostatin receptors have been identified in many tissues throughout the human body. Alterations in the expression of somatostatin receptors have been reported in many disease states including both tumorous and nontumorous conditions. Somatostatin receptor scintigraphy utilizing OctreoScan (Mallinckrodt Medical, Inc., St. Louis, MO), a radiolabled form of octreotide, has been reported to be a highly sensitive imaging technique for identifying pathology, such as neuroendocrine tumors, that are somatostatin receptor dense. Unfortunately, many conditions cause an increase in the quantity of somatostatin receptors and therefore may cause false positive Octreoscans. In this report, we discuss the alterations in somatostatin receptors that occur with Crohn's disease and describe a case of an OctreoScan-positive inflammatory mass mimicking a carcinoid tumor.

Objective: To determine the frequency of fractures and associated factors in women with systemic lupus erythematosus (SLE)., Methods: Women with SLE (n = 304) completed this cross-sectional study conducted from 1996 to 2002. Self-reported fractures occurring after the diagnosis of SLE were evaluated. Hip and/or lumbar spine bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry, and the results were expressed as BMD Z-scores. Multiple logistic regression analyses were performed to identify factors associated with fractures., Results: Of the 304 women with SLE, 12.5% experienced fractures. Those with fractures had significantly lower BMD Z-scores at the hip (Fracture group -0.55 vs No Fracture group -0.14, group difference 0.41; 95% CI 0.04 to 0.78), but not at the lumbar spine (Fracture group -0.25 vs No Fracture group -0.18, group difference 0.07; 95% CI -0.43 to 0.57). Among women with fractures, 60.5% and 63.2% had normal BMD Z-scores (BMD Z-score > -1.0) at the hip and lumbar spine, respectively, and 50.0% had normal BMD Z-scores at both anatomical sites. In multiple logistic regression analysis, each year of disease duration (adjusted OR 1.11; 95% CI 1.05 to 1.17) and use of osteoporosis medications (adjusted OR 4.75; 95% CI 1.62 to 13.94) were significantly associated with fractures., Conclusion: . Longer duration of SLE and use of osteoporosis medications were significantly associated with fractures. Although women with fractures had significantly lower BMD Z-scores at the hip, an unexpectedly high proportion of women with SLE having normal BMD Z-score experienced fractures following SLE diagnosis.

Objective: To determine the association between race/ethnicity and bone mineral density (BMD) in women with systemic lupus erythematosus (SLE)., Methods: Women with SLE (n = 298), including 77 African Americans and 221 whites, completed this cross-sectional study conducted from 1996 to 2002. Hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry. Study participants completed a self-administered questionnaire and a physician completed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). BMD results were expressed as Z scores. Analyses were performed to identify factors, including race/ethnicity, associated with low BMD defined as a Z score -1.0 or less at the hip or lumbar spine., Results: African Americans compared with whites were younger at study visit (mean +/- SD 39.7 +/- 8.4 years versus 42.9 +/- 11.6 years) and had higher SDI (mean +/- SD 1.8 +/- 2.0 versus 1.0 +/- 1.6), but similar proportions of women were postmenopausal (31.2% versus 38.0%). African Americans had significantly lower mean BMD Z scores at the hip (-0.49 versus -0.07; group difference -0.41; 95% confidence interval [95% CI] -0.70, -0.13) and at the lumbar spine (-1.03 versus 0.10; group difference -1.13; 95% CI -1.48, -0.78) compared with whites. African American race/ethnicity was strongly associated with low BMD at the lumbar spine (adjusted odds ratio 4.42; 95% CI 2.19, 8.91) but not at the hip, adjusting for factors associated with low BMD., Conclusion: African American women compared with white women with SLE had lower BMD at the hip and lumbar spine. African American race/ethnicity was associated with low BMD at the lumbar spine controlling for relevant clinical covariates.

Background: [18F]Fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan is widely used for the staging evaluation of nonsmall cell lung cancer, however, its use in small cell lung cancer (SCLC) remains investigational., Patient and Methods: We designed a prospective study to evaluate the role of PET in SCLC. Patients with SCLC underwent PET scanning as well as conventional imaging before and after treatment., Results: A total of 39 PET scan examinations were performed in 21 patients with SCLC; 18 studies were performed before first-line chemotherapy and 21 studies were done during or after treatment. PET findings were compared with findings on CT scans of the chest or abdomen and bone scan. Discordant findings were detected in 14 out of 383 comparisons (4%) for 10 anatomic sites. In the thorax and the abdomen, PET agreed with CT scan in 92% to 100% of examinations assessing potential disease sites, including the contralateral chest, liver, and adrenals. PET agreed with bone scan in detecting bony lesions in 27 out of 32 imaging studies (84%): in 4 out of 5 discordant cases, PET findings were true and in 1 case indeterminate. Staging at baseline (limited, n = 6; extensive, n = 12) was identical when PET and sum of other staging procedures were compared. Response assessment was concordant between PET and CT scans in 8 of 9 patients who had evaluation before and after first-line chemotherapy., Conclusions: PET is potentially useful for the initial staging and monitoring of patients with SCLC and it may be superior to bone scan in detecting bone metastasis. The cost effectiveness of PET scan in SCLC remains to be determined.

This report presents updated time-to-event variables from a multicenter phase II trial of reduced-dose 90Y ibritumomab tiuxetan in patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL) and mild thrombocytopenia (platelet counts of 100 to 149 x 10(9) platelets/L). Patients received a single course of ibritumomab tiuxetan radioimmunotherapy, with 90Y ibritumomab tiuxetan administered at 0.3 mCi/kg (compared to a standard dose of 0.4 mCi/kg). In 30 patients, the overall response rate was 83%, with complete responses (confirmed [CR] and unconfirmed [CRu]) of 47%. Median follow-up time is currently 36.5 months (range: 7.5-54.9+ months). Median duration of response was 11.5 months (range: 1.0-53.9 months), median time to progression was 9.4 months (range: 1.7-54.8+ months), and median time to next lymphoma therapy was 14.6 months (range: 2.3-54.9 months). Median overall survival time has not yet been reached. Long-term responses, defined as time to progression of 12 months or greater, have been seen in 14 of 30 patients (47%) overall, and 12 of 14 CR/CRu patients (86%). Toxicities were primarily hematologic and reversible. No additional long-term adverse events have been observed in the follow-up period, and treatment did not preclude subsequent lymphoma therapies., (Copyright Mary Ann Liebert, Inc.)

Paragangliomas are indolent tumors that arise from the chief cells of the paraganglia in the head and neck, mediastinum, and retroperitoneal regions. Less than 10% of paragangliomas metastasize. Paragangliomas are known to regress slowly and usually partially after radiation therapy, which has been attributed to the development of fibrosis within the abundant vascular elements of the tumor. Positron emission tomography (PET) scanning was used to monitor a 33-year-old woman with recurrent paraganglioma of the carotid body with lung and bone metastases before and after chemotherapy with cyclophosphamide, doxorubicin (Adriamycin), and dacarbazine. The patient derived clinical benefit from chemotherapy, with marked improvement of her systemic and respiratory symptoms, improvement of cancer-related anemia, and normalization of chromogranin A levels. A response was demonstrated on PET scan with decreased [18F] fluoro-2-deoxy-d-glucose uptake after chemotherapy, but no significant changes were detected on serial computed tomography (CT) scans. The patient has remained free of disease progression 24 months after chemotherapy completion. It is suggested that metabolic imaging with PET scans is superior to anatomical imaging with CT scans for the monitoring of patients with paragangliomas.

Unlabelled: Ibritumomab tiuxetan is an anti-CD20 murine IgG1 kappa monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates (111)In for imaging or dosimetry and (90)Y for radioimmunotherapy (RIT). Dosimetry and pharmacokinetic data from 4 clinical trials of (90)Y-ibritumomab tiuxetan RIT for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) were combined and assessed for correlations with toxicity data., Methods: Data from 179 patients were available for analysis. Common eligibility criteria included <25% bone marrow involvement by NHL, no prior myeloablative therapy, and no prior RIT. The baseline platelet count was required to be > or = 100,000 cells/mm(3) for the reduced (90)Y-ibritumomab tiuxetan administered dose (7.4-11 MBq/kg [0.2-0.3 mCi/kg]) or > or = 150,000 cells/mm(3) for the standard (90)Y-ibritumomab tiuxetan administered dose (15 MBq/kg [0.4 mCi/kg]). Patients were given a tracer administered dose of 185 MBq (5 mCi) (111)In-ibritumomab tiuxetan on day 0, evaluated with dosimetry, and then a therapeutic administered dose of 7.4-15 MBq/kg (0.2-0.4 mCi/kg) (90)Y-ibritumomab tiuxetan on day 7. Both ibritumomab tiuxetan administered doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve ibritumomab tiuxetan biodistribution. Residence times for (90)Y in blood and major organs were estimated from (111)In biodistribution, and the MIRDOSE3 computer software program was used, with modifications to account for patient-specific organ masses, to calculate radiation absorbed doses to organs and red marrow., Results: Median radiation absorbed doses for (90)Y were 7.42 Gy to spleen, 4.50 Gy to liver, 2.11 Gy to lung, 0.23 Gy to kidney, 0.62 Gy (blood-derived method) and 0.97 Gy (sacral image-derived method) to red marrow, and 0.57 Gy to total body. The median effective blood half-life was 27 h, and the area under the curve (AUC) was 25 h. No patient failed to meet protocol-defined dosimetry safety criteria and all patients were eligible for treatment. Observed toxicity was primarily hematologic, transient, and reversible. Hematologic toxicity did not correlate with estimates of red marrow radiation absorbed dose, total-body radiation absorbed dose, blood effective half-life, or blood AUC., Conclusion: Relapsed or refractory NHL in patients with adequate bone marrow reserve and <25% bone marrow involvement by NHL can be treated safely with (90)Y-ibritumomab tiuxetan RIT on the basis of a fixed, weight-adjusted dosing schedule. Dosimetry and pharmacokinetic results do not correlate with toxicity.

Mildly thrombocytopenic patients with relapsed or refractory low-grade non-Hodgkin lymphoma (NHL) have an increased risk of chemotherapy-induced myelosuppression following treatment. The safety and efficacy of radioimmunotherapy with a reduced dose of (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]; maximum 32 mCi [1.2 GBq]) was evaluated in 30 patients with mild thrombocytopenia (100-149 x 10(9) platelets/L) who had advanced, relapsed or refractory, low-grade, follicular, or transformed B-cell NHL. The ibritumomab tiuxetan regimen included an infusion of rituximab (250 mg/m(2)) and injection of (111)In ibritumomab tiuxetan (5 mCi [185 MBq]) for dosimetry evaluation, followed 1 week later with rituximab (250 mg/m(2)) and (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]). Patients (median age, 61 years; 90% stage III/IV at study entry; 83% follicular lymphoma; and 67% with bone marrow involvement) had a median of 2 prior therapy regimens (range, 1-9). Estimated radiation-absorbed doses were well below the study-defined maximum allowable for all 30 patients. With the use of the International Workshop criteria for NHL response assessment, the overall response rate was 83% (37% complete response, 6.7% complete response unconfirmed, and 40% partial response). Kaplan-Meier estimated median time to progression (TTP) was 9.4 months (range, 1.7-24.6). In responders, Kaplan-Meier estimated median TTP was 12.6 months (range, 4.9-24.6), with 35% of data censored. Toxicity was primarily hematologic, transient, and reversible. The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 33%, 13%, and 3%, respectively. Reduced-dose ibritumomab tiuxetan is safe and well tolerated and has significant clinical activity in this patient population.