Attenuation correction (AC) of whole-body PET data in combined PET/MRI tomographs is expected to be a technical challenge. In this study, a potential solution based on a segmented attenuation map is proposed and evaluated in clinical PET/CT cases. Methods: Segmentation of the attenuation map into 4 classes (background, lungs, fat, and soft tissue) was hypothesized to be sufficient for AC purposes. The segmentation was applied to CT-based attenuation maps from 18 F-FDG PET/CT oncologic examinations of 35 patients with 52 18 F-FDG-avid lesions in the lungs (n 5 15), bones (n 5 21), and neck (n 5 16). The standardized uptake values (SUVs) of the lesions were determined from PET images reconstructed with nonsegmented and segmented attenuation maps, and an experienced observer interpreted both PET images with no knowledge of the attenuation map status. The feasibility of the method was also evaluated with 2 patients who underwent both PET/CT and MRI. Results: The use of a segmented attenuation map resulted in average SUV changes of 8% 6 3% (mean 6 SD) for bone lesions, 4% 6 2% for neck lesions, and 2% 6 3% for lung lesions. The largest SUV change was 13.1%, for a lesion in the pelvic bone. There were no differences in the clinical interpretations made by the experienced observer with both types of attenuation maps. Conclusion: A segmented attenuation map with 4 classes derived from CT data had only a small effect on the SUVs of 18 F-FDGavid lesions and did not change the interpretation for any patient. This approach appears to be practical and valid for MRI-based AC.Key Words: instrumentation; PET/CT; PET/MRI; attenuation correction J Nucl Med 2009; 50:520-526 DOI: 10.2967/jnumed.108.054726 Int he same way in which PET/CT has been shown to be a powerful multimodality imaging tool, there are compelling reasons for combining PET and MRI. PET/MRI would have the following advantages: improved soft-tissue contrast; the possibility of performing truly simultaneous instead of sequential acquisitions; and the availability of sophisticated MRI sequences, such as diffusion and perfusion imaging, functional MRI, and MR spectroscopy, which can add important information. Moreover, the use of PET/MRI would result in a significant decrease in radiation exposure, which is of foremost importance for serial follow-up and pediatric imaging.Thus, a combined PET/MRI scanner would provide an alternative to a combined PET/CT scanner for whole-body oncologic imaging (1,2); improved accuracy could be achieved in the detection, staging, and characterization of several cancers (3-10). Moreover, the combination of PETand MRI is perfectly suited to neurologic imaging and offers new possibilities for cardiovascular imaging (11,12). Consequently, much research effort is being directed toward the development of combined imaging devices, and the initial results are promising (13-18).However, a still-unsolved technical challenge for combined whole-body PET/MRI is the correction of attenuation and scatter in the PET data (19). For this purpose, an...
The combination of magnetic resonance imaging (MR) and positron emission tomography (PET) scanners can provide a powerful tool for clinical diagnosis and investigation. Among the challenges of developing a combined scanner, obtaining attenuation maps for PET reconstruction is of critical importance. This requires accounting for the presence of MR hardware in the field of view. The attenuation introduced by this hardware cannot be obtained from MR data. We propose the creation of attenuation models of MR hardware, to be registered into the MR-based attenuation map prior to PET reconstruction. Two steps were followed to assess the viability of this method. First, transmission and emission measurements were performed on MR components (RF coils and medical probes). The severity of the artifacts in the reconstructed PET images was evaluated. Secondly, a high-exposure computed tomography (CT) scan was used to obtain a model of a head coil. This model was registered into the attenuation map of PET/CT scans of a uniform phantom fitted with the coil. The resulting PET images were compared to the PET/CT reconstruction in the absence of coils. The artifacts introduced by misregistration of the model were studied. The transmission scans revealed 17% count loss due to the presence of head and neck coils in the field of view. Important sources of attenuation were found in the lock, signal cables and connectors. However, the worst source of attenuation was the casing between both coils. None of the measured medical probes introduced a significant amount of attenuation. Concerning the attenuation model of the head coil, reconstructed PET images with model-based correction were comparable to the reference PET/CT reconstruction. However, inaccuracies greater than 1-2 mm in the axial positioning of the model led to important artifacts. In conclusion, the results show that model-based attenuation correction is possible. Using a high-exposure scan to create an attenuation model of the coils has been proved feasible. However, adequate registration of the model is mandatory.
Background: Various trivalent radiometals are well suited for labeling of DOTA-conjugated variants of Glu-ureido-based prostate-specific membrane antigen (PSMA) inhibitors. The DOTA-conjugate PSMA-617 has proven high potential in PSMA radioligand therapy (PSMA-RLT) of prostate cancer as well as PET imaging when labeled with lutetium-177 and gallium-68 respectively. Considering the relatively short physical half-life of gallium-68 this positron emitter precludes prolonged acquisition periods, as required for pre-therapeutic dosimetry or intraoperative applications. In this context, the positron emitter scandium-44 is an attractive alternative for PET imaging. We report the synthesis of [44Sc]Sc-PSMA-617 as radiopharmaceutical with generator produced scandium-44, its in vitro characterization and clinical translation as part of a first in-human study.Methods: Scandium-44 was obtained from a 44Ti/44Sc radionuclide generator. PSMA-617 was labeled with 142.4±12.7 MBq of scandium-44 in analogy to [68Ga]Ga-PSMA-617 and evaluated in vitro and in cell studies using PSMA+ LNCaP cells. A first-in-human investigation was subsequently carried out in a cohort of 4 patients (mean age 70±1.8 a) registered for [177Lu]Lu-PSMA-617 therapy. 50.5±9.3 MBq (40 µg, 38.4 nmol) [44Sc]Sc-PSMA-617 were applied via intravenous injection (i.v.), respectively. A Siemens Biograph 2 PET/CT system was used to acquire initial dynamic PET data (30 min) of abdomen in list mode followed by static PET/CT data (skull to mid-thigh) at 45 min, 2 and 18 h post-injection (p.i.). For quantitative analysis, dynamic images were reconstructed as 6 data sets of 300 s each. The noise ratio was measured in liver, lung and an additional region outside the body. SUV values in different organs and lesions were measured and compared to [68Ga]Ga-PSMA-11 data of the same patients. Residence times and organ absorbed doses were calculated using OLINDA/EXM software.Results: Quantitative radiochemical yields of ≥98 % were achieved using 18 nmol of PSMA-617 after 20 min at 95 °C with apparent molar activity of 6.69±0.78 MBq/nmol. Following purification, >99 % radiochemical purity was obtained. [44Sc]Sc-PSMA-617 showed high stability (>95 %) in serum for 24 h. The binding affinity and internalization fraction were determined in PSMA+ LNCaP cells (IC50 = 4.72±0.7 nM and internalization fraction: 15.78±2.14 % IA/106 LNCaP cells) and compared to [68Ga]Ga-PSMA-11 (12.0±2.8 nM and 9.47±2.56 % IA/106 LNCaP cells). Physiological tracer uptake was observed in kidneys, liver, spleen, small intestine, urinary bladder, and salivary glands and pathological uptake in both soft and skeletal metastases. SUV values were significantly lower in the kidneys (14.0) compared to [68Ga]Ga-PSMA-11 OET (30.5). All other measured SUV values did not show a statistically significant difference. Tumor to liver ratios were found to lie between 1.9 and 8.3 for [68Ga]Ga-PSMA-11 and between 2.5 and 8.8 for [44Sc]Sc-PSMA-617 after 120 min. For [44Sc]Sc-PSMA-617 the ratios were higher and no statistically sig...
The importance of personalized medicine has been growing, mainly due to a more urgent need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for specific molecular targeting, both for diagnostics and therapy. The visualization of potential targets can help predict if a patient will benefit from a particular treatment. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents has been continually increasing. In this article, important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with a well-known radioiodine therapy in patients with thyroid cancer and then progresses through various approaches for the treatment of advanced cancer with targeted therapies. The aim of this review was to provide a summary of background knowledge and current applications, and to identify the advantages of targeted therapies and imaging in nuclear medicine practices.
18 F-FDG PET/CT is effective in the assessment of therapy response. Changes in glucose uptake or tumor size are used as a measure. Tumor heterogeneity was found to be a promising predictive and prognostic factor. We investigated textural parameters for their predictive and prognostic capability in patients with rectal cancer using histopathology as the gold standard. In addition, a comparison to clinical outcome was performed. Methods: Twenty-seven patients with rectal cancer underwent 18 F-FDG PET/CT before, 2 wk after the start, and 4 wk after the completion of neoadjuvant chemoradiotherapy. In all PET/CT scans, conventional parameters (tumor volume, diameter, maximum and mean standardized uptake values, and total lesion glycolysis [TLG]) and textural parameters (coefficient of variation [COV], skewness, and kurtosis) were determined to assess tumor heterogeneity. Values on pretherapeutic PET/CT as well as changes early in the course of therapy and after therapy were compared with histopathologic response. In addition, the prognostic value was assessed by correlation with time to progression and survival time. Results: The COV showed a statistically significant capability to assess histopathologic response early in therapy (sensitivity, 68%; specificity, 88%) and after therapy (79% and 88%, respectively). Thereby, the COV had a higher area under the curve in receiver-operating-characteristic analysis than did any analyzed conventional parameter for early and late response assessment. The COV showed a statistically significant capability to evaluate disease progression and to predict survival, although the latter was not statistically significant. Conclusion: Tumor heterogeneity assessed by the COV, being superior to the investigated conventional parameters, is an important predictive factor in patients with rectal cancer. Furthermore, it can provide prognostic information. Therefore, its application is an important step for personalized treatment of rectal cancer.
Purpose: To evaluate the dependency of the sensitivity of [11 C]choline positron emission tomography/ computed tomography (PET/CT) for detecting and localizing primary prostate cancer (PCa) on tumor configuration in the histologic specimen. Experimental Design: Forty-three patients with biopsy-proven PCa were included. They underwent radical prostatectomy within 31 days after [11 C]choline PET/CT. The transaxial image slices and the histologic specimens were analyzed by comparing the respective slices. Maximum standardized uptake values (SUV max ) were calculated in each segment and correlated with histopathology. The tumor configuration in the histologic specimen was grouped as: I, unifocal; II, multifocal; III, rind-like shaped; IV, size <5 mm. Data analysis included the investigation of detection of PCa by SUV max , the assessment of the influence of potential contributing factors on tumor prediction, and the evaluation of whether SUV could discriminate cancer tissue from benign prostate hyperplasia (BPH), prostatitis, HGPIN (high-grade prostate intraepithelial neoplasm), or normal prostate tissue. General estimation equation models were used for statistical analysis.Results: Tumor configuration in histology was classified as I in 21 patients, as II in 9, as III in 5, and as IV in 8. The prostate segment involved by cancer is identified in 79% of the patients. SUV max was located in the same side of the prostate in 95% of patients. Tumor configuration was the only factor significantly negatively influencing tumor prediction (P < 0.001). PCa-SUV max (median SUV max ¼ 4.9) was not significantly different from BPH-SUV (median SUV max ¼ 4.5) and prostatitis-SUV (median SUV max ¼ 3.9), P ¼ 0.102 and P ¼ 0.054, respectively.Conclusions: The detection and localization of PCa in the prostate with [ 11 C]choline PET/CT is impaired by tumor configuration. Additionally, in our patient population, PCa tissue could not be distinguished from benign pathologies in the prostate.
BackgroundTextural features in FDG-PET have been shown to provide prognostic information in a variety of tumor entities. Here we evaluate their predictive value for recurrence and prognosis in NSCLC patients receiving primary stereotactic radiation therapy (SBRT).Methods45 patients with early stage NSCLC (T1 or T2 tumor, no lymph node or distant metastases) were included in this retrospective study and followed over a median of 21.4 months (range 3.1–71.1). All patients were considered non-operable due to concomitant disease and referred to SBRT as the primary treatment modality. Pre-treatment FDG-PET/CT scans were obtained from all patients. SUV and volume-based analysis as well as extraction of textural features based on neighborhood gray-tone difference matrices (NGTDM) and gray-level co-occurence matrices (GLCM) were performed using InterView Fusion™ (Mediso Inc., Budapest). The ability to predict local recurrence (LR), lymph node (LN) and distant metastases (DM) was measured using the receiver operating characteristic (ROC). Univariate and multivariate analysis of overall and disease-specific survival were executed.Results7 out of 45 patients (16%) experienced LR, 11 (24%) LN and 11 (24%) DM. ROC revealed a significant correlation of several textural parameters with LR with an AUC value for entropy of 0.872. While there was also a significant correlation of LR with tumor size in the overall cohort, only texture was predictive when examining T1 (tumor diameter < = 3 cm) and T2 (>3 cm) subgroups. No correlation of the examined PET parameters with LN or DM was shown.In univariate survival analysis, both heterogeneity and tumor size were predictive for disease-specific survival, but only texture determined by entropy was determined as an independent factor in multivariate analysis (hazard ratio 7.48, p = .016). Overall survival was not significantly correlated to any examined parameter, most likely due to the high comorbidity in our cohort.ConclusionsOur study adds to the growing evidence that tumor heterogeneity as described by FDG-PET texture is associated with response to radiation therapy in NSCLC. The results may be helpful into identifying patients who might profit from an intensified treatment regime, but need to be verified in a prospective patient cohort before being incorporated into routine clinical practice.
BackgroundPreclinical biodistribution and dosimetric analysis of [177Lu]Lu-DOTAZOL suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [177Lu]Lu-DOTAZOL in patients with metastatic skeletal disease.MethodFour patients with metastatic skeletal disease (age range, 64–83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.3 mCi) of [177Lu]Lu-DOTAZOL. Biodistribution was assessed with serial planar whole body scintigraphy at 20 min and 3, 24, and 167 h post injection (p.i.) and blood samples at 20 min and 3, 8, 24, and 167 h p.i. Percent of injected activity in the blood, kidneys, urinary bladder, skeleton, and whole body was determined. Bone marrow self-dose was determined by an indirect blood-based method. Urinary bladder wall residence time was calculated using Cloutier’s dynamic urinary bladder model with a 4-h voiding interval. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) software was used to determine residence times in source organs by applying biexponential curve fitting and to calculate organ absorbed dose.ResultsQualitative biodistribution analysis revealed early and high uptake of [177Lu]Lu-DOTAZOL in the kidneys with fast clearance showing minimal activity by 24 h p.i. Activity in the skeleton increased gradually over time. Mean residence times were found to be highest in the skeleton followed by the kidneys. Highest mean organ absorbed dose was 3.33 mSv/MBq for osteogenic cells followed by kidneys (0.490 mSv/MBq), red marrow (0.461 mSv/MBq), and urinary bladder wall (0.322 mSv/MBq). The biodistribution and normal organ absorbed doses of [177Lu]Lu-DOTAZOL are consistent with preclinical data.Conclusion[177Lu]Lu-DOTAZOL shows maximum absorbed doses in bone and low kidney doses, making it a promising agent for radionuclide therapy of bone metastasis. Further studies are warranted to evaluate the efficacy and safety of radionuclide therapy with [177Lu]Lu-DOTAZOL in the clinical setting.
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