Lymphocyte Function at Baseline Could Be a New Predictor of Tumor Burden following Six Cycles of Radium-223 Therapy in Patients with Metastasized, Castration-Resistant Prostate Cancer.

Previous data indicate that one cycle of treatment with radium-223 (223Ra) did not significantly impair lymphocyte function in patients with metastasized, castration-resistant prostate cancer. The aim of the current study was to assess in 21 patients whether six cycles of this therapy had an effect on lymphocyte proliferation and interferon-γ and interleukin (IL)-10 ELISpot results. Lymphocyte proliferation after stimulation with microbial antigens and the production of interferon-γ continuously decreased after six cycles of radionuclide therapy, reaching statistical significance (p < 0.05) at months 1, 2, 4, and/or 6 after therapy. One month after the last cycle of therapy, 67% of patients showed a decrease in tumor burden. The tumor burden correlated negatively with IL-10 secretion at baseline, e.g., after stimulation with tetanus antigen (p < 0.0001, r = -0.82). As determined by receiver operating characteristic (ROC) curve analysis, tetanus-specific IL-10 spots at baseline had the highest predictive value (p = 0.005) for tumor burden at month 6, with an area under the curve (AUC) of 0.90 (sensitivity 100%, specificity 78%). In conclusion, we observed an additive effect of treatment with 223Ra on immune function and found that IL-10 secretion at baseline predicted tumor burden at month 6 after treatment.

Impact of germline polymorphisms in genes regulating glucose uptake on positron emission tomography findings and outcome in diffuse large B-cell lymphoma: results from the PETAL trial.

BACKGROUND: [18F]Fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging procedure in diffuse large B-cell lymphoma (DLBCL). Disease presentation, FDG-PET/CT performance, and outcome may be influenced by germline single nucleotide polymorphisms (SNP) in genes regulating glucose uptake. METHODS: Clinical variables, FDG-PET findings, and outcome were analysed in relation to SNPs in 342 DLBCL patients participating in the 'Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas' (PETAL) trial. Genes analysed included SLC2A1 (SNPs rs1385129, referred to as HaeIII; rs710218, HpyCH4V; rs841853, XbaI), VEGFA (rs3025039), HIF1A (rs11549465, P582S; rs11549467, A588T), and APEX1 (rs1130409, D148E). Statistical significance was assumed at p ≤ 0.05. RESULTS: The SLC2A1 HaeIII and HpyCH4V SNPs were tightly linked and statistically significantly associated with baseline maximum standardized uptake value (SUVmax) and Ann Arbor stage, with slightly lower SUVmax (HaeIII, median 18.9, interquartile range [IQR] 11.5-26.6, versus 21.6, IQR 14.4-29.7; p = 0.019) and more frequent stage IV disease (HaeIII, 44.5% versus 30.8%; p = 0.011) in minor allele carriers. As previously reported for lung cancer, the association was dependent upon the coexistent APEX1 D148E genotype. The HIF1A A588T SNP was associated with total metabolic tumour volume (TMTV) and time-to-progression, with significantly lower TMTV (median 16 cm3, IQR 7-210, versus 146 cm3, IQR 34-510; p = 0.034) and longer time-to-progression in minor allele carriers (log-rank p = 0.094). Time-to-progression was also associated with the SLC2A1 XbaI and APEX1 D148E SNPs, with shorter time-to-progression in homozygous and heterozygous SLC2A1 XbaI (HR 1.456; CI 0.930-2.280; p = 0.099) and homozygous APEX1 D148E minor allele carriers (HR 1.6; CI 1.005-2.545; p = 0.046). In multivariable analyses including SNPs, International Prognostic Index factors, sex, and B symptoms, HIF1A A588T, SLC2A1 XbaI, and APEX1 D148E retained statistical significance for time-to-progression, and SLC2A1 XbaI was also significantly associated with overall survival. CONCLUSIONS: Common SNPs in genes regulating glucose uptake may impact SUVmax, tumour distribution, tumour volume, and outcome in DLBCL. The effects on SUVmax are of low magnitude and appear clinically negligible. The results are consistent with findings in other types of cancer. They need to be confirmed in an independent DLBCL population of sufficient size. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov NCT00554164; EudraCT 2006-001641-33. Registration date November 5, 2007, https://www. CLINICALTRIALS: gov/ct2/show/NCT00554164.

Interim PET Evaluation in Diffuse Large B-Cell Lymphoma Using Published Recommendations: Comparison of the Deauville 5-Point Scale and the ΔSUVmax Method.

The value of interim 18F-FDG PET/CT (iPET)-guided treatment decisions in patients with diffuse large B-cell lymphoma (DLBCL) has been the subject of much debate. This investigation focuses on a comparison of the Deauville score and the change-in-SUVmax (ΔSUVmax) approach-2 methods to assess early metabolic response to standard chemotherapy in DLBCL. Methods: Of 609 DLBCL patients participating in the PET-Guided Therapy of Aggressive Non-Hodgkin Lymphomas trial, iPET scans of 596 patients originally evaluated using the ΔSUVmax method were available for post hoc assessment of the Deauville score. A commonly used definition of an unfavorable iPET result according to the Deauville score is an uptake greater than that of the liver, whereas an unfavorable iPET scan with regard to the ΔSUVmax approach is characterized as a relative reduction of the SUVmax between baseline and iPET staging of less than or equal to 66%. We investigated the 2 methods' correlation and concordance by Spearman rank correlation coefficient and the agreement in classification, respectively. We further used Kaplan-Meier curves and Cox regression to assess differences in survival between patient subgroups defined by the prespecified cutoffs. Time-dependent receiver-operating-characteristic curve analysis provided information on the methods' respective discrimination performance. Results: Deauville score and ΔSUVmax approach differed in their iPET-based prognosis. The ΔSUVmax approach outperformed the Deauville score in terms of discrimination performance-most likely because of a high number of false-positive decisions by the Deauville score. Cutoff-independent discrimination performance remained low for both methods, but cutoff-related analyses showed promising results. Both favored the ΔSUVmax approach, for example, for the segregation by iPET response, where the event-free survival hazard ratio was 3.14 (95% confidence interval, 2.22-4.46) for ΔSUVmax and 1.70 (95% confidence interval, 1.29-2.24) for the Deauville score. Conclusion: When considering treatment intensification, the currently used Deauville score cutoff of an uptake above that of the liver seems to be inappropriate and associated with potential harm for DLBCL patients. The ΔSUVmax criterion of a relative reduction in SUVmax of less than or equal to 66% should be considered as an alternative.

Impact of complete surgical resection on outcome in aggressive non-Hodgkin lymphoma treated with immunochemotherapy.

BACKGROUND: Surgical resection is considered to be of purely diagnostic value in aggressive lymphoma. Evidence for an impact on outcome is scant and restricted to retrospective observations. METHODS: In the "Positron Emission Tomography-guided Therapy of Aggressive non-Hodgkin Lymphomas" (PETAL) trial, patients with a negative baseline positron emission tomography (PET) scan were documented in a prospective observational substudy. Baseline PET-negative patients with the absence of lymph node enlargement on computed tomography and a negative bone marrow biopsy were considered to have undergone complete lymphoma resection. RESULTS: Eighty-two of 1,041 patients (7.9%) had a negative baseline PET scan, and 67 were included in this analysis. All were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), plus rituximab for CD20-positive lymphomas. Among 52 patients with diffuse large B-cell lymphoma (DLBCL), 48 had completely resected disease. Their outcome tended to be better than that of 115 baseline PET-positive stage I DLBCL patients treated in the main part of the PETAL trial (2-year progression-free survival 92.7% [95% confidence interval 84.7-100] versus 88.4% [82.5-94.3], P = .056; 2-year overall survival 92.7% [84.7-100] versus 93.7% [89.2-98.2], P = .176), but this was restricted to patients below the age of 60 years (2-year progression-free survival 100% versus 92.2% [84.8-99.6], P = .031; 2-year overall survival 100% versus 95.9% [90.2-100], P = .075). In peripheral T-cell lymphoma, eight of 11 patients had completely resected disease. In contrast to DLBCL, complete resection was not associated with improved outcome compared to the control. CONCLUSION: Young patients with early stage DLBCL may benefit from complete lymphoma resection prior to immunochemotherapy.

Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial.

The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV41max ) and SUV4 thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUVmax approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)-positive lymphoma were analyzed separately from patients with ALK-negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression-free survival, with thresholds best dichotomizing the population, of 232 cm3 using SUV41max and 460 cm3 using SUV4 . For iPET response, the respective thresholds were 46.9% SUVmax reduction and Deauville score 1-4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV41max and SUV4 , and 29% and 25% for iPET response by ΔSUVmax and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135-4.624) for SUV41max and 3.206 (1.524-6.743) for SUV4 . At iPET, it was 3.910 (1.891-8.087) for ΔSUVmax and 4.371 (2.079-9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651-22.336]). Due to small numbers and events, PET did not predict survival in ALK-positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK-negative T-cell lymphoma for early allogeneic transplantation or innovative therapies.

Metabolic tumor volume, cancer cell fraction, and prognosis - the case of T-cell/histiocyte-rich large B-cell lymphoma.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare aggressive lymphoma characterized by a paucity of neoplastic B-cells and a majority of reactive T-cells with or without histiocytes. In the 'Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas' trial (clinicaltrials.gov NCT00554164; EudraCT 2006-001641-33), its frequency was less than 3%. While cancer cell content by quantitative histology was 10-times lower, baseline total metabolic tumor volume (TMTV) by 18-fluorodesoxyglucose positron emission tomography was 10-times higher in THRLBCL than in diffuse large B-cell lymphoma (DLBCL). When THRLBCL and DLBCL populations were matched for TMTV, the survival curves were superimposable. However, when the populations were matched for cancer cell volume by multiplying TMTV by cancer cell fraction, outcome in THRLBCL was worse than in DLBCL. Whether genetic differences between cancer cells, tumor-promoting properties of non-neoplastic cells, or both are responsible for inferior cancer cell volume-related outcome in THRLBCL, remains to be elucidated.

Supporting data for positron emission tomography-based risk modelling using a fixed-instead of a relative thresholding method for total metabolic tumor volume determination.

Total metabolic tumor volume (TMTV) was measured in 510 patients with DLBCL participating in the PETAL trial. The present data provide information about the prognostic impact of total metabolic tumor volume using the fixed standardized uptake value (SUV4) instead of the relative SUV41max thresholding method. A Bland-Altman plot was created to compare both methods. For TMTV assessed by the SUV4 method a Cox regression was applied to determine its effect on time to progression, progression-free survival, and overall survival. Kaplan-Meier curves and corresponding hazard ratios were used to estimate the effect of TMTV alone or in combination with interim positron emission tomography response on patients' survival. The data relate to the research article entitled "Dynamic risk assessment based on positron emission tomography scanning in diffuse large B-cell lymphoma: post-hoc analysis from the PETAL trial" [1].

Dynamic risk assessment based on positron emission tomography scanning in diffuse large B-cell lymphoma: Post-hoc analysis from the PETAL trial.

BACKGROUND: Valid prognostic tools are needed to guide risk-adjusted treatment approaches in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: We assessed total metabolic tumor volume (TMTV) and standardized uptake value (SUV)-based interim positron emission tomography (iPET) response in 510 patients with DLBCL participating in the positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL) trial (NCT00554164). TMTV was analyzed with a relative (SUV41max) and a fixed thresholding method (SUV4), and iPET was evaluated using the ΔSUVmax procedure. We determined associations between TMTV and international prognostic index (IPI) factors using Welch's t-test, investigated effects of TMTV, iPET response, and the IPI factors on time to progression (TTP), progression-free survival (PFS), and overall survival (OS) by Cox regression, and estimated the outcome using Kaplan-Meier curves. FINDINGS: TMTV was associated with all IPI factors except age. Irrespective of the thresholding method used, TMTV and iPET response were correlated with TTP, PFS, and OS, and remained the only independent outcome predictors in Cox regression analysis. By dichotomizing TMTV (cut-off: 328 cm³ by SUV41max) and iPET response (cut-off: 66% SUVmax reduction), we defined three groups at different risk of treatment failure (low [57.1% of patients]: low TMTV/good iPET response; intermediate [37.8%]: high TMTV/good iPET response or low TMTV/poor iPET response; and high [5.1%]: high TMTV/poor iPET response), with corresponding 2-year probabilities of 93.8% vs. 67.3% vs. 38.5% for TTP, 90.9% vs. 62.5% vs. 29.9% for PFS, and 95.5% vs. 77.4% vs. 37.1% for OS. INTERPRETATION: The PET-based risk model proposed may help identify patients who may benefit from treatment modifications or novel approaches.

Six versus eight doses of rituximab in patients with aggressive B cell lymphoma receiving six cycles of CHOP: results from the "Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas" (PETAL) trial.

Standard first-line treatment of aggressive B cell lymphoma comprises six or eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus eight doses of rituximab (R). Whether adding two doses of rituximab to six cycles of R-CHOP is of therapeutic benefit has not been systematically investigated. The Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial investigated the ability of [18F]-fluorodesoxyglucose PET scanning to guide treatment in aggressive non-Hodgkin lymphomas. Patients with B cell lymphomas and a negative interim scan received six cycles of R-CHOP with or without two extra doses of rituximab. For reasons related to trial design, only about a third underwent randomization between the two options. Combining randomized and non-randomized patients enabled subgroup analyses for diffuse large B cell lymphoma (DLBCL; n = 544), primary mediastinal B cell lymphoma (PMBCL; n = 37), and follicular lymphoma (FL) grade 3 (n = 35). With a median follow-up of 52 months, increasing the number of rituximab administrations failed to improve outcome. A non-significant trend for improved event-free survival was seen in DLBCL high-risk patients, as defined by the International Prognostic Index, while inferior survival was observed in female patients below the age of 60 years. Long-term outcome in PMBCL was excellent. Differences between FL grade 3a and FL grade 3b were not apparent. The results were confirmed in a Cox proportional hazard regression model and a propensity score matching analysis. In conclusion, adding two doses of rituximab to six cycles of R-CHOP did not improve outcome in patients with aggressive B cell lymphomas and a fast metabolic treatment response.

[Selective intraarterial radiotherapy (SIRT) of malignant liver tumors]. / Selektive intraarterielle Radiotherapie (SIRT) maligner Lebertumoren.

Die Leitlinie soll medizinisches Fachpersonal und onkologisch tätige Ärzte bei der Auswahl geeigneter Patienten, der Planung, Vorbereitung und Durchführung einer SIRT zur Behandlung primärer und sekundärer maligner Lebertumoren unterstützen. Schwerpunkte sind personelle, technische und organisatorische Anforderungen an das Therapiezentrum einschließlich Strahlenschutz, d. h. insbesondere die Notwendigkeit einer interdisziplinären Patientenselektion in Tumorboards und die Anforderungen an das Team, das die Therapie durchführt und einen Medizinphysikexperten einbeziehen muss. Die Zielsetzung der Therapie, die erforderlichen Daten und Voruntersuchungen für die Indikationsstellung und Therapieplanung und ihre Implikationen für die Vermeidung von Komplikationen werden dargestellt, ebenso Anforderungen an die Aufklärung des Patienten. Die Nachsorge wird beschrieben und auf die Notwendigkeit einer interdisziplinären Zusammenarbeit auch mit heimatnahen behandelnden Ärzten hingewiesen.

Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer.

PURPOSE: Therapy with the alpha-emitter radium-223 chloride (223Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if 223Ra therapy induces an impairment of cellular antimicrobial immune responses. METHODS: In 11 patients receiving 223Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. RESULTS: Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. CONCLUSIONS: The results argue against an impairment of lymphocyte function after 223Ra therapy. Thus, immune responses against pathogens should remain unaffected.

Identification and Tumour-Binding Properties of a Peptide with High Affinity to the Disialoganglioside GD2.

Neuroectodermal tumours are characterized by aberrant processing of disialogangliosides concomitant with high expression of GD2 or GD3 on cell surfaces. Antibodies targeting GD2 are already in clinical use for therapy of neuroblastoma, a solid tumour of early childhood. Here, we set out to identify peptides with high affinity to human disialoganglioside GD2. To this end, we performed a combined in vivo and in vitro screen using a recombinant phage displayed peptide library. We isolated a phage displaying the peptide sequence WHWRLPS that specifically binds to the human disialoganglioside GD2. Binding specificity was confirmed by mutational scanning and by comparative analyses using structurally related disialogangliosides. In vivo, significant enrichment of phage binding to xenografts of human neuroblastoma cells in mice was observed. Tumour-specific phage accumulation could be blocked by intravenous coinjection of the corresponding peptide. Comparative pharmacokinetic analyses revealed higher specific accumulation of 68Ga-labelled GD2-binding peptide compared to 111In-labelled peptide in xenografts of human neuroblastoma. In contrast to 124I-MIBG, which is currently evaluated as a neuroblastoma marker in PET/CT, 68Ga-labelled GD2-specific peptide spared the thyroid but was enriched in the kidneys, which could be partially blocked by infusion of amino acids.In summary, we here report on a novel tumour-homing peptide that specifically binds to the disialoganglioside GD2, accumulates in xenografts of neuroblastoma cells in mice and bears the potential for tumour detection using PET/CT. Thus, this peptide may serve as a new scaffold for diagnosing GD2-positive tumours of neuroectodermal origin.

The Treatment of Well-Differentiated Thyroid Carcinoma.

BACKGROUND: Recent decades have seen a rise in the incidence of well-differentiated (mainly papillary) thyroid carcinoma around the world. In Germany, the age-adjusted incidence of well-differentiated thyroid carcinoma in 2010 was 3.5 per 100 000 men and 8.7 per 100 000 women per year. METHODS: This review is based on randomized, controlled trials and multicenter trials on the treatment of well-differentiated thyroid carcinoma that were retrieved by a selective literature search, as well as on three updated guidelines issued in the past two years. RESULTS: The recommended extent of surgical resection depends on whether the tumor is classified as low-risk or high-risk, so that papillary microcarcinomas, which carry a highly favorable prognosis, will not be overtreated. More than 90% of localized, well-differentiated thyroid carcinomas can be cured with a combination of surgery and radioactive iodine therapy. Radioactive iodine therapy is also effective in the treatment of well-differentiated thyroid carcinomas with distant metastases, yielding a 10-year survival rate of 90%, as long as there is good iodine uptake and the tumor goes into remission after treatment; otherwise, the 10-year survival rate is only 10%. In the past two years, better treatment options have become available for radioactive-iodine-resistant thyroid carcinoma. Phase 3 studies of two different tyrosine kinase inhibitors have shown that either one can markedly prolong progression-free survival, but not overall survival. Their more common clinically significant side effects are hand-foot syndrome, hypertension, diarrhea, proteinuria, and weight loss. CONCLUSION: Slow tumor growth, good resectability, and susceptibility to radioactive iodine therapy lend a favorable prognosis to most cases of well-differentiated thyroid carcinoma. The treatment should be risk-adjusted and interdisciplinary, in accordance with the current treatment guidelines. Even metastatic thyroid carcinoma has a favorable prognosis as long as there is good iodine uptake. The newly available medical treatment options for radioactive-iodine-resistant disease need to be further studied.

Cabozantinib in progressive medullary thyroid cancer.

PURPOSE: Cabozantinib, a tyrosine kinase inhibitor (TKI) of hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2, and rearranged during transfection (RET), demonstrated clinical activity in patients with medullary thyroid cancer (MTC) in phase I. PATIENTS AND METHODS: We conducted a double-blind, phase III trial comparing cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomly assigned (2:1) to cabozantinib (140 mg per day) or placebo. The primary end point was progression-free survival (PFS). Additional outcome measures included tumor response rate, overall survival, and safety. RESULTS: The estimated median PFS was 11.2 months for cabozantinib versus 4.0 months for placebo (hazard ratio, 0.28; 95% CI, 0.19 to 0.40; P < .001). Prolonged PFS with cabozantinib was observed across all subgroups including by age, prior TKI treatment, and RET mutation status (hereditary or sporadic). Response rate was 28% for cabozantinib and 0% for placebo; responses were seen regardless of RET mutation status. Kaplan-Meier estimates of patients alive and progression-free at 1 year are 47.3% for cabozantinib and 7.2% for placebo. Common cabozantinib-associated adverse events included diarrhea, palmar-plantar erythrodysesthesia, decreased weight and appetite, nausea, and fatigue and resulted in dose reductions in 79% and holds in 65% of patients. Adverse events led to treatment discontinuation in 16% of cabozantinib-treated patients and in 8% of placebo-treated patients. CONCLUSION: Cabozantinib (140 mg per day) achieved a statistically significant improvement of PFS in patients with progressive metastatic MTC and represents an important new treatment option for patients with this rare disease. This dose of cabozantinib was associated with significant but manageable toxicity.

Performance of a high-sensitivity dedicated cardiac SPECT scanner for striatal uptake quantification in the brain based on analysis of projection data.

PURPOSE: The authors have previously reported the advantages of high-sensitivity single-photon emission computed tomography (SPECT) systems for imaging structures located deep inside the brain. DaTscan (Isoflupane I-123) is a dopamine transporter (DaT) imaging agent that has shown potential for early detection of Parkinson disease (PD), as well as for monitoring progression of the disease. Realizing the full potential of DaTscan requires efficient estimation of striatal uptake from SPECT images. They have evaluated two SPECT systems, a conventional dual-head gamma camera with low-energy high-resolution collimators (conventional) and a dedicated high-sensitivity multidetector cardiac imaging system (dedicated) for imaging tasks related to PD. METHODS: Cramer-Rao bounds (CRB) on precision of estimates of striatal and background activity concentrations were calculated from high-count, separate acquisitions of the compartments (right striata, left striata, background) of a striatal phantom. CRB on striatal and background activity concentration were calculated from essentially noise-free projection datasets, synthesized by scaling and summing the compartment projection datasets, for a range of total detected counts. They also calculated variances of estimates of specific-to-nonspecific binding ratios (BR) and asymmetry indices from these values using propagation of error analysis, as well as the precision of measuring changes in BR on the order of the average annual decline in early PD. RESULTS: Under typical clinical conditions, the conventional camera detected 2 M counts while the dedicated camera detected 12 M counts. Assuming a normal BR of 5, the standard deviation of BR estimates was 0.042 and 0.021 for the conventional and dedicated system, respectively. For an 8% decrease to BR = 4.6, the signal-to-noise ratio were 6.8 (conventional) and 13.3 (dedicated); for a 5% decrease, they were 4.2 (conventional) and 8.3 (dedicated). CONCLUSIONS: This implies that PD can be detected earlier with the dedicated system than with the conventional system; therefore, earlier identification of PD progression should be possible with the high-sensitivity dedicated SPECT camera.

Improved regional activity quantitation in nuclear medicine using a new approach to correct for tissue partial volume and spillover effects.

We have developed a new method of compensating for effects of partial volume and spillover in dual-modality imaging. The approach requires segmentation of just a few tissue types within a small volume-of-interest (VOI) surrounding a lesion; the algorithm estimates simultaneously, from projection data, the activity concentration within each segmented tissue inside the VOI. Measured emission projections were fitted to the sum of resolution-blurred projections of each such tissue, scaled by its unknown activity concentration, plus a global background contribution obtained by reprojection through the reconstructed image volume outside the VOI. The method was evaluated using multiple-pinhole µSPECT data simulated for the MOBY mouse phantom containing two spherical lung tumors and one liver tumor, as well as using multiple-bead phantom data acquired on µSPECT and µCT scanners. Each VOI in the simulation study was 4.8 mm (12 voxels) cubed and, depending on location, contained up to four tissues (tumor, liver, heart, lung) with different values of relative (99m)Tc concentration. All tumor activity estimates achieved bias after ∼ 15 ordered-subsets expectation maximization (OSEM) iterations (×10 subsets) , with better than 8% precision ( ≤ 25% greater than the Cramer-Rao lower bound). The projection-based fitting approach also outperformed three standardized uptake value (SUV)-like metrics, one of which was corrected for count spillover. In the bead phantom experiment, the mean ± standard deviation of the bias of VOI estimates of bead concentration were 0.9±9.5%, comparable to those of a perturbation geometric transfer matrix (pGTM) approach (-5.4±8.6%); however, VOI estimates were more stable with increasing iteration number than pGTM estimates, even in the presence of substantial axial misalignment between µCT and µSPECT image volumes.

Influence of various geometric factors on the iodine-131 uptake measurement for solitary thyroid nodules.

AIM: The influence of various geometric factors on I uptake measurements for solitary thyroid nodule was systematically investigated to derive an approach, based on routinely performed ultrasound examinations, to correct for the effect of geometric variations. METHODS: The influence of size, shape, and position of a thyroid nodule, neck-to-detector distance and neck curvature on the uptake value was analyzed with a three-dimensional model. Uptake measurements using a tissue-equivalent neck phantom were carried out to verify the calculated correction factors and also to check the influence of scatter. Sonograms of 92 patients with solitary nodules were analyzed to correct for geometric variations. RESULTS: The correction factors were independent of the size and shape of the nodule, and the activity distribution of the solitary nodules can be approximated by a point source. The correction factors were mainly determined by the nodular depth and by the accuracy of the neck-to-detector distance and were affected to a lesser extent by the lateral position of the nodule as well as the curvature of the neck. The effect of scatter can be neglected if the energy window largely excludes Compton scatter, as is the case in the I uptake measurement. The ultrasound-derived correction factors ranged from 0.85 to 1.25. CONCLUSION: The proposed approach is capable of correcting for the geometric variation for a solitary nodule and can be easily applied in routine clinics. The accuracy of absorbed dose in radioiodine therapy can be improved in particular for nodules located well beneath the neck surface.