Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

OBJECTIVES: To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. BACKGROUND: RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. METHODS: Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. RESULTS: Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. CONCLUSION: RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

Assessment of operability by means of CTPA and perfusion SPECT in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) can potentially be cured by pulmonary thrombendarterectomy (PEA), the criteria for differentiation between operable and non-operable patients are not standardized. PURPOSE: To retrospectively evaluate the value of rigidly registered computed tomography pulmonary angiography (CTPA) and single photon emission CT (SPECT) in differentiating for PEA. MATERIAL AND METHODS: Forty-nine patients with CTEPH (21 men; age, 58 ± 13 years) were evaluated by an interdisciplinary expert board using all available diagnostic information and their consensus statement as gold standard. For SPECT a lobe based perfusion score was visually assessed using the score of 0 (lack of perfusion) to 1 (normal perfusion) calculating percentage of vascular obstruction (PVO). By CTPA, vascular obstruction index (OI) of central, peripheral, and global PA-bed were determined. The accuracy of the alignment between CTPA and SPECT was determined by fusion score (FS) ranging from 1 (no alignment) to 5 (exact alignment). Angiography provided PA pressure (PAP), pulmonary vascular resistance (PVR), and PA wedge pressure (PAWP). Receiver operating characteristics (ROC) analysis was performed. RESULTS: Twenty-nine patients were considered surgically amenable, and 20 patients were inoperable. Mean PAP, PVR, and PAWP were 48 ± 11 mmHg, 868 ± 461 dynes*sec*cm(-5), and 11 ± 5 mmHg, without differences between surgical and non-surgical patients (P > 0.5). In all patients accurate registration was reached (FS = 4.1 ± 0.7; range, 2-5). PVO and central OI separated PEA-amenable patients (P ≤ 0.001) resulting in the area under the curve of 0.828 (cutoff for PVO: 37.8% with a sensitivity of 82% and specificity of 79%) and 0.755 (cutoff for central OI: 29% with a sensitivity and specificity of 86.2% and 79%) for operability. CONCLUSION: An accurate interpretation of rigidly registered CTPA and perfusion SPECT may contribute to stratification of operability in patients with CTEPH.

PET-based delineation of tumour volumes in lung cancer: comparison with pathological findings.

PURPOSE: The objective of the study was to validate an adaptive, contrast-oriented thresholding algorithm (COA) for tumour delineation in (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for non-small cell lung cancer (NSCLC) in comparison with pathological findings. The impact of tumour localization, tumour size and uptake heterogeneity on PET delineation results was also investigated. METHODS: PET tumour delineation by COA was compared with both CT delineation and pathological findings in 15 patients to investigate its validity. Correlations between anatomical volume, metabolic volume and the pathology reference as well as between the corresponding maximal diameters were determined. Differences between PET delineations and pathological results were investigated with respect to tumour localization and uptake heterogeneity. RESULTS: The delineated volumes and maximal diameters measured on PET and CT images significantly correlated with the pathology reference (both r > 0.95, p < 0.0001). Both PET and CT contours resulted in overestimation of the pathological volume (PET 32.5 ± 26.5%, CT 46.6 ± 27.4%). CT volumes were larger than those delineated on PET images (CT 60.6 ± 86.3 ml, PET 48.3 ± 61.7 ml). Maximal tumour diameters were similar for PET and CT (51.4 ± 19.8 mm for CT versus 53.4 ± 19.1 mm for PET), slightly overestimating the pathological reference (mean difference CT 4.3 ± 3.2 mm, PET 6.2 ± 5.1 mm). PET volumes of lung tumours located in the lower lobe were significantly different from those determined from pathology (p = 0.037), whereas no significant differences were observed for tumours located in the upper lobe (p = 0.066). Only minor correlation was found between pathological tumour size and PET heterogeneity (r = -0.24). CONCLUSION: PET tumour delineation by COA showed a good correlation with pathological findings. Tumour localization had an influence on PET delineation results. The impact of tracer uptake heterogeneity on PET delineation should be considered carefully and individually in each patient. Altogether, PET tumour delineation by COA for NSCLC patients is feasible and reliable with the potential for routine clinical application.

Simultaneous occurrence of typical carcinoid and non-small-cell lung cancer in the same lung lobe: value of nuclear medicine.

The present report demonstrates the usefulness of nuclear medicine in differentiating different pulmonary tumors. A 79-year-old woman presented with a suspicious peripherally located lesion of the right lower lobe in the costophrenic angle. During bronchoscopic evaluation, a centrally located intrabronchial lesion was found, which was positive on a subsequent In-111 octreotide examination. The histologic examination of this central lesion confirmed a typical bronchial carcinoid. The FDG PET examination revealed a high uptake just in the peripherally located lesion, which was then confirmed to be non-small-cell lung cancer. This is the first report of nuclear medicine methods evaluating simultaneous occurrence of a typical bronchial carcinoid and a non-small-cell lung cancer in the same lung lobe.

F-18-FDG-PET confined radiotherapy of locally advanced NSCLC with concomitant chemotherapy: results of the PET-PLAN pilot trial.

PURPOSE: The integration of fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the process of radiotherapy (RT) planning of locally advanced non-small-cell lung cancer (NSCLC) may improve diagnostic accuracy and minimize interobserver variability compared with target volume definition solely based on computed tomography. Furthermore, irradiating only FDG-PET-positive findings and omitting elective nodal regions may allow dose escalation by treating smaller volumes. The aim of this prospective pilot trial was to evaluate the therapeutic safety of FDG-PET-based RT treatment planning with an autocontour-derived delineation of the primary tumor. METHODS AND MATERIALS: Eligible patients had Stages II-III inoperable NSCLC, and simultaneous, platinum-based radiochemotherapy was indicated. FDG-PET and computed tomography acquisitions in RT treatment planning position were coregistered. The clinical target volume (CTV) included the FDG-PET-defined primary tumor, which was autodelineated with a source-to-background algorithm, plus FDG-PET-positive lymph node stations. Limited by dose restrictions for normal tissues, prescribed total doses were in the range of 66.6 to 73.8 Gy. The primary endpoint was the rate of out-of-field isolated nodal recurrences (INR). RESULTS: As per intent to treat, 32 patients received radiochemotherapy. In 15 of these patients, dose escalation above 66.6 Gy was achieved. No Grade 4 toxicities occurred. After a median follow-up time of 27.2 months, the estimated median survival time was 19.3 months. During the observation period, one INR was observed in 23 evaluable patients. CONCLUSIONS: FDG-PET-confined target volume definition in radiochemotherapy of NSCLC, based on a contrast-oriented source-to-background algorithm, was associated with a low risk of INR. It might provide improved tumor control because of dose escalation.

FP-CIT SPECT does not predict the progression of motor symptoms in Parkinson's disease.

BACKGROUND/AIMS: FP-CIT (fluoropropyl-2ß-carbomethoxy-3ß-4-iodophenyl-nortroptane) SPECT is a well-established nuclear medicine method to support the clinical diagnosis of Parkinson's disease (PD). In this study, we examined the prognostic value of FP-CIT SPECT concerning the PD motor symptoms. METHODS: All 38 PD patients (age 57 ± 7 years, Hoehn & Yahr stage 1.6 ± 0.8, mean ± SD) underwent a baseline visit and a follow-up visit 3-7 years (5.2 ± 1.3 years) after the baseline visit. Cerebral [(123)I]FP-CIT SPECT was performed only once at the baseline visit. At both visits the motor symptoms bradykinesia, rigidity, resting tremor, postural tremor and axial symptoms were quantified by means of the UPDRS motor scale. RESULTS: There was no significant correlation between the initial striatal FP-CIT uptake and the annual progress of any motor symptom (= difference [(motor symptom at follow-up visit) - (motor symptom at baseline visit)]/time (in years) between assessments). CONCLUSION: The initial striatal FP-CIT SPECT does not predict the velocity of progress of PD motor symptoms within an interval of 3-7 years.

Myocardial MIBG scintigraphy may predict the course of motor symptoms in Parkinson's disease.

BACKGROUND: The metaiodobenzylguanidine (MIBG) scintigraphy is a well established nuclear medicine method to support the clinical diagnosis of Parkinson's disease. In this study we examined the predictive value of the MIBG scintigraphy concerning the severity and progression of the parkinsonian motor symptoms. PATIENTS AND METHODS: This study included 40 patients with idiopathic Parkinson's disease (age 56 ± 9 years, Hoehn and Yahr stage 1.4 ± 0.7, mean ± standard deviation). All patients underwent a baseline visit and a follow-up visit 3-8 years (5.3 ± 1.6 years) after the baseline visit. (123)I-MIBG scintigraphy was performed only once at the baseline visit. At both visits the motor symptoms bradykinesia, rigidity, resting tremor, postural tremor and axial symptoms were quantified by means of the motor part of the Unified Parkinson's disease rating scale. RESULTS: The myocardial MIBG uptake correlated significantly with the annual progress of rigidity (r=-0.41, p<0.05; Pearson's correlation) and axial symptoms (r=-0.49, p<0.01). There was no significant correlation (p>0.05) between the initial myocardial MIBG uptake and the annual progress of the other motor symptoms. CONCLUSION: The MIBG scintigraphy may predict the velocity of progress of rigidity and axial symptoms in the following 3-8 years. Such a prediction is not possible for the other motor symptoms resting tremor, postural tremor and bradykinesia.

Impact of rigid and nonrigid registration on the determination of 18F-FDG PET-based tumour volume and standardized uptake value in patients with lung cancer.

PURPOSE: Assessment of the metabolically active tumour tissue by FDG PET is evolving for use in the diagnosis of non-small-cell lung cancer (NSCLC), in the planning of radiotherapy, and in follow-up and response evaluation. For exact evaluation accurate registration of PET and CT data is required. The registration process is usually based on rigid algorithms; however, nonrigid algorithms are increasingly being used. The influence of the registration method on FDG PET-based standardized uptake value (SUVmax) and metabolic tumour volume (MTV) definition has not yet been evaluated. We compared intra- and interindividual differences in SUV and MTV between rigid- and nonrigid-registered PET and CT acquired during different breathing manoeuvres. METHODS: The study group comprised 28 radiotherapy candidates with histologically proven NSCLC who underwent FDG PET acquisition and three CT acquisitions (expiration - EXP, inspiration - INS, mid-breath-hold - MID). All scans were registered with both a rigid (R) and a nonrigid (NR) procedure resulting in six fused datasets: R-INS, R-EXP, R-MID, NR-INS, NR-EXP and NR-MID. For the delineation of MTVs a contrast-oriented contouring algorithm developed in-house was used. To accelerate the delineation a semiautomatic software prototype was utilized. RESULTS: Tumour mean SUVmax did not differ for R and NR registration (R 17.5 ± 7, NR 17.4 ± 7; p=0.2). The mean MTV was higher by 3 ± 12 ml (p=0.02) in the NR group than in the R group, as was the mean tumour diameter (by 0.1 ± 0.2 cm; p<0.01). With respect to the three different breathing manoeuvres, there were no differences in MTV in the R group (p > 0.7). In intraindividual comparison there were no significant differences in MTVs concerning the registration pairs R-EXP (68 ± 88 ml) vs. NR-EXP (69 ± 85 ml) und R-MID (68 ± 86 ml) vs. NR-MID (69 ± 83 ml) (both p > 0.4). However, the MTVs were larger after NR registration during inspiration (R-INS 68 ± 82 vs. NR-INS 78 ± 93 ml; p=0.02). CONCLUSION: The use of nonrigid algorithms may lead to a change in MTV, whose extent is influenced by the breathing manoeuvre on CT. Nonrigid registration methods cannot be recommended for the definition of MTV if the CT scan is performed during inspiration. The choice of registration algorithm has no significant impact on SUVmax.

Prospective study of p-[123I]iodo-L-phenylalanine and SPECT for the evaluation of newly diagnosed cerebral lesions: specific confirmation of glioma.

PURPOSE: The differentiation between gliomas, metastases and gliotic or inflammatory lesions by imaging techniques remains a challenge. Gliomas frequently exhibit increased uptake of radiolabelled amino acids and are thus amenable to PET or SPECT imaging. Recently, p-[123I]iodo-L-phenylalanine (IPA) was validated for the visualization of glioma by SPECT and received orphan drug status. Here we investigated its diagnostic performance for differentiating indeterminate brain lesions. METHODS: This prospective open study included 67 patients with newly diagnosed brain lesions suspicious for glioma (34 without and 33 with contrast enhancement in the MRI scan). Patients received 250 MBq IPA intravenously after overnight fasting. SPECT images at 30 min and 3 h post-injection were iteratively reconstructed and visually interpreted after image fusion with an MRI brain scan (fluid-attenuated inversion recovery sequence or T1-weighted contrast-enhanced image). Findings were correlated with results of stereotactic or open biopsies or serial imaging. RESULTS: Twenty-seven low-grade (2 WHO I, 25 WHO II) and 24 high-grade gliomas (1 WHO III, 23 WHO IV), 3 metastases originating from lung cancer as well as 13 non-neoplastic lesions were proven. All non-neoplastic lesions and all metastases were negative with IPA SPECT. Forty gliomas were true-positive (TP) and 11 false-negative (FN) findings (8 WHO II, 1 WHO III, 2 WHO IV) occurred. There were no false-positive (FP) findings. For the differentiation of primary brain tumours and non-neoplastic lesions, sensitivity and specificity were 78 and 100%. In 34 lesions without contrast enhancement in MRI, IPA SPECT resulted in 17 TP, 8 true-negative, 9 FN and no FP findings (sensitivity 65%, specificity 100%). CONCLUSION: In patients with suspected glioma, IPA SPECT shows a high specificity, but especially in low-grade gliomas FN findings may occur. Due to the high positive predictive value a positive finding allows a suspected glioma to be confirmed.

PET scans in radiotherapy planning of lung cancer.

Especially for non-small cell lung cancer, FDG-PET has in the majority of the patients led to the safe decrease of radiotherapy volumes, enabling radiation-dose escalation and, experimentally, redistribution of radiation doses within the tumor. In limited-disease small cell lung cancer, the role of FDG-PET is emerging.

High rates of durable responses with anti-CD22 fractionated radioimmunotherapy: results of a multicenter, phase I/II study in non-Hodgkin's lymphoma.

PURPOSE: Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. RESULTS: At the maximum total (90)Y dose of 45 mCi/m(2) (1,665 MBq/m(2)), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and (90)Y doses, even in poor-risk categories (refractory to last anti-CD20-containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total (90)Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m(2) total (90)Y-dose [1,110 MBq/m(2)]). Further, patients with FL refractory to prior anti-CD20-containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. CONCLUSION: Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.

Risk stratification of solitary pulmonary nodules by means of PET using (18)F-fluorodeoxyglucose and SUV quantification.

PURPOSE: (18)F-fluorodeoxyglucose (FDG) PET is the most accurate imaging modality in characterizing a solitary pulmonary nodule (SPN). Besides visual image interpretation, semiquantitative analysis using standardized uptake values (SUV) is performed to improve diagnostic accuracy. Mostly, an SUV threshold of 2.5 is applied to differentiate between benign and malignant lesions. In this study we analysed the use different SUV thresholds to predict the post-test probability of malignancy for the individual patient considering his pre-test probability. Furthermore, we investigated the prognostic value of SUV in SPN for survival. METHODS: This retrospective study included 140 consecutive patients who underwent FDG PET for evaluation of SPN. Visual interpretation was performed by two readers. For semiquantitative analysis, maximum SUV (SUV(max)) was measured in all SPN. A final diagnosis was obtained by pathological examination or follow-up of more than 2 years. In a nomogram, positive and negative predictive values (PPV and NPV) were plotted against the hypothetical SUV threshold to determine the optimum SUV threshold. Survival was analysed using the Kaplan-Meier method and log-rank test. RESULTS: The prevalence of malignancy was 57%. The FDG uptake in malignant SPNs was higher than in benign SPNs (SUV 9.7 +/- 5.5 vs 2.6 +/- 2.5, p < 0.01). More than 90% of SPNs with an SUV below 2.0 were benign (sensitivity, specificity, NPV of 96, 55 and 92%). The highest diagnostic accuracy was achieved with an SUV of 4.0 (sensitivity, specificity and accuracy of 85%). Visual interpretation achieved corresponding values of 94, 70 and 84%, respectively. In lung cancer higher FDG uptake (SUV(max) >or= 9.5) was associated with shorter survival (median survival 20 months) and low FDG uptake with longer survival (>75 months). CONCLUSION: FDG PET allows assessment of the individual risk for malignancy in SPNs by considering tumoural SUV and pre-test probability. Higher FDG uptake in lung cancer as measured by SUV analysis is a prognostic factor. In patients with low FDG uptake in an SPN and increased risk during surgery omission of diagnostic thoracotomy may be warranted.

Nonrigid versus rigid registration of thoracic 18F-FDG PET and CT in patients with lung cancer: an intraindividual comparison of different breathing maneuvers.

UNLABELLED: In lung cancer, (18)F-FDG PET, CT, and (18)F-FDG PET/CT are used for noninvasive staging and therapy planning. Even with improved image registration techniques-especially in the modern hybrid PET/CT scanners-inaccuracies in the fusion process may occur, leading to errors in image interpretation. The aim of this study was to investigate by an intraindividual analysis whether, in comparison with a rigid algorithm, a nonrigid registration algorithm improves the quality of fusion between (18)F-FDG PET and CT. METHODS: Sixteen patients with histologically proven non-small cell lung cancer underwent a thoracic (18)F-FDG PET acquisition in radiotherapy treatment position and 3 CT acquisitions (expiration, inspiration, and mid breath-hold) on the same day. All scans were registered with rigid and nonrigid procedures, resulting in 6 fused datasets: rigid inspiration, rigid expiration, rigid mid breath-hold, nonrigid inspiration, nonrigid expiration, and nonrigid mid breath-hold. The quality of alignment was assessed by 3 experienced readers at 8 anatomic landmarks: lung apices, aortic arch, heart, spine, sternum, carina, diaphragm, and tumor using an alignment score ranging from 1 (no alignment) to 5 (exact alignment). RESULTS: Nonrigid PET/CT showed better alignment than rigid PET/CT (3.5 +/- 0.7 vs. 3.3 +/- 0.7, P < 0.001). Regarding the breathing maneuver, no difference between nonrigid mid breath-hold and rigid mid breath-hold was observed. In contrast, the alignment quality significantly improved from rigid expiration to nonrigid expiration (3.4 +/- 0.7 vs. 3.6 +/- 0.7, P < 0.001) and from rigid inspiration to nonrigid inspiration (3.1 +/- 0.7 vs. 3.3 +/- 0.7, P < 0.001). With regard to individual landmarks, an improvement in fusion quality through the use of nonrigid registration was obvious at the lung apices, carina, and aortic arch. CONCLUSION: The alignment quality of thoracic (18)F-FDG PET/CT exhibits a marked dependence on the breathing maneuver performed during the CT acquisition, as demonstrated in an intraindividual comparison. Nonrigid registration is a significant improvement over rigid registration if the CT is performed during full inspiration or full expiration. The best fusion results are obtained with the CT performed at mid breath-hold using rigid registration, without an improvement using nonrigid algorithms.

Efficacy of systemic radionuclide therapy with p-131I-iodo-L-phenylalanine combined with external beam photon irradiation in treating malignant gliomas.

UNLABELLED: p-(131)I-iodo-L-phenylalanine ((131)I-IPA) is a tumor-specific amino acid derivative that demonstrated antiproliferative and tumoricidal effects on experimental gliomas. This study tested the efficacy of (131)I-IPA combined with external beam photon radiotherapy as a new therapeutic approach against gliomas. METHODS: Glioma cells derived from the rat F98 glioma or human Tx3868 or A1207 glioblastoma cell lines were stereotactically inoculated into the brains of Fischer 344 rats or RNU rats. Tumor formation was verified radiologically. On day 8, groups of glioma-bearing rats of each tumor model underwent whole-brain radiotherapy with 8 Gy, an intravenous administration of (131)I-IPA (30 MBq), or combined treatment, aiming for a total of 12 rats per group. Another 12 animals were treated with physiologic saline and served as control. RESULTS: Control rats had a combined median survival (+/-SD) of 21 +/- 6 d. All revealed metabolically and histologically large tumor masses. Efficacy of radiotherapy alone or a monotherapy with 30 MBq of (131)I-IPA was statistically insignificant on the syngeneic Fischer-F98 model (P >or= 0.45 and P = 0.10, respectively). In contrast, a subset of long-term survivors (>120 d) was observed in RNU rats bearing Tx3868 and A1207 glioblastoma xenografts (18%-25% and 35%-45% for radiotherapy and (131)I-IPA, respectively). Combined (131)I-IPA and radiotherapy treatment significantly prolonged median survival for the syngeneic Fischer-F98 glioma model (P < 0.01) and human glioblastoma-bearing RNU rats alike (P < 0.05). On day 120 after monotherapy with (131)I-IPA, 45% of the RNU rats were still alive, but after 8 Gy of photon radiotherapy only 18%-25% of the RNU and none of the Fischer rats survived. In comparison, 55%-75% survival rates were registered after combined treatment on day 120 for all animal models. CONCLUSION: These data convincingly demonstrated that systemic radionuclide therapy with (131)I-IPA combined with external photon radiotherapy is a safe and highly effective treatment for experimental gliomas, which may merit a clinical trial to ascertain its potential in patients with gliomas. Because only a low (131)I-IPA activity and low radiotherapy doses were applied, further optimizations including higher radiation doses and conventional fractionated radiotherapy are warranted.

FDG-PET-based radiotherapy planning in lung cancer: optimum breathing protocol and patient positioning--an intraindividual comparison.

PURPOSE: Fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET) and PET/computed tomography (CT) are increasingly used for radiotherapy (RT) planning in patients with non-small-cell lung carcinoma. The planning process often is based on separately acquired FDG-PET/CT and planning CT scans. We compared intraindividual differences between PET acquired in diagnostic (D-PET) and RT treatment position (RT-PET) coregistered with planning CTs acquired using different breathing protocols. METHODS AND MATERIALS: Sixteen patients with non-small-cell lung carcinoma underwent two PET acquisitions (D-PET and RT-PET) and three planning CT acquisitions (expiration [EXP], inspiration [INS], and mid-breath hold [MID]) on the same day. All scans were rigidly coregistered, resulting in six fused data sets: D-INS, D-EXP, D-MID, RT-INS, RT-EXP, and RT-MID. Fusion accuracy was assessed by three readers at eight anatomic landmarks, lung apices, aortic arch, heart, spine, sternum, carina, diaphragm, and tumor, by using an alignment score ranging from 1 (no alignment) to 5 (exact alignment). RESULTS: The RT-PET showed better alignment with any CT than D-PET (p < 0.001). With regard to breathing, RT-MID showed the best mean alignment score (3.7 +/- 1.0), followed by RT-EXP (3.5 +/- 0.9) and RT-INS (3.0 +/- 0.8), with all differences significant (p < 0.001). Comparing alignment scores with regard to anatomic landmarks, the largest deviations were found at the diaphragm, heart, and apices. Overall, there was fair agreement (kappa = 0.48; p < 0.001) among the three readers. CONCLUSIONS: Significantly better fusion of PET and planning CT can be reached with PET acquired in the RT position. The best intraindividual fusion results are obtained with the planning CT performed during mid-breath hold. Our data justify the acquisition of a separate planning PET in RT treatment position if only a diagnostic PET scan is available.

Combining 153Sm-lexidronam and docetaxel for the treatment of patients with hormone-refractory prostate cancer: first experience.

PURPOSE: 153Sm-lexidronam has been used for the palliation of symptoms from painful bone metastases for years, while docetaxel has recently been shown to improve the survival of patients with hormone-refractory prostate cancer (HRPC). The first clinical experience with the combination of both treatment modalities is reported. METHODS: Between 2005 and 2006, 12 patients with muliple bone metastases from HRPC were treated with a single application of 37 MBq/kg body weight 153Sm-lexidronam and 6 weekly infusions of 35 mg/m2 docetaxel. Data on survival, prostate-specific antigen (PSA) response, symptom palliation, toxicity, and scintigraphic follow-up are provided. RESULTS: Mean follow-up was 11.4 (range, 1.1-25.8) months, overall 1-year survival was 48.6%, and median survival was 11.5 months. A PSA response of >50% was documented in 50% of patients. The average pain score (visual analog scale: 1-10) was reduced from 5.1 to 1.4 (p = 0.016) with decrease of > or =2 in 58.3% of patients. The average World Health Organization medication level dropped from 1.6 to 1.1 (p = 0.5). Overall toxicity was moderate, but 1 patient died due to neutropenic sepsis. CONCLUSIONS: Our analysis demonstrates feasibility and therapeutic potential for the combination treatment and merits prospective investigation. Further studies will be planned with respect to the potentially synergistic hematologic toxicity of bone-seeking radiopharmaceuticals and chemotherapy.

A contrast-oriented algorithm for FDG-PET-based delineation of tumour volumes for the radiotherapy of lung cancer: derivation from phantom measurements and validation in patient data.

PURPOSE: An easily applicable algorithm for the FDG-PET-based delineation of tumour volumes for the radiotherapy of lung cancer was developed by phantom measurements and validated in patient data. METHODS: PET scans were performed (ECAT-ART tomograph) on two cylindrical phantoms (phan1, phan2) containing glass spheres of different volumes (7.4-258 ml) which were filled with identical FDG concentrations. Gradually increasing the activity of the fillable background, signal-to-background ratios from 33:1 to 2.5:1 were realised. The mean standardised uptake value (SUV) of the region-of-interest (ROI) surrounded by a 70% isocontour (mSUV(70)) was used to represent the FDG accumulation of each sphere (or tumour). Image contrast was defined as C=(mSUV(70)-BG)/BG where BG is the mean background - SUV. For the spheres of phan1, the threshold SUVs (TS) best matching the known sphere volumes were determined. A regression function representing the relationship between TS/(mSUV(70) - BG) and C was calculated and used for delineation of the spheres in phan2 and the gross tumour volumes (GTVs) of eight primary lung tumours. These GTVs were compared to those defined using CT. RESULTS: The relationship between TS/(mSUV(70) - BG) and C is best described by an inverse regression function which can be converted to the linear relationship TS=a x mSUV(70)+b x BG. Using this algorithm, the volumes delineated in phan2 differed by only -0.4 to +0.7 mm in radius from the true ones, whilst the PET-GTVs differed by only -0.7 to +1.2 mm compared with the values determined by CT. CONCLUSION: By the contrast-oriented algorithm presented in this study, a PET-based delineation of GTVs for primary tumours of lung cancer patients is feasible.

Intra-individual comparison of p-[123I]-iodo-L-phenylalanine and L-3-[123I]-iodo-alpha-methyl-tyrosine for SPECT imaging of gliomas.

OBJECTIVES: Radioactive amino-acids accumulate in gliomas even with an intact blood-brain-barrier. L-3-[(123)I]-iodo-alpha-methyl-tyrosine (IMT) is well established for SPECT imaging of gliomas. Recently, we introduced p-[(123)I]-iodo-L-phenylalanine (IPA) for the characterisation of brain lesions. This study compares both tracers in glioma patients. METHODS: Eleven patients with gliomas (1 WHO grade 1, 5 grade 2, 1 grade 3, 2 grade 4 gliomas, 1 unconfirmed upgrading and 1 post-therapeutic non-neoplastic lesion) underwent SPECT imaging with IPA (early and delayed acquisitions at 30 min and 3 h) and IMT (early only). Maximum tumour-to-brain ratios (TBR) were calculated using region-of-interest analysis to assess uptake of IMT and IPA. Imaging results were compared to histopathological findings. RESULTS: Early TBRs of IMT and IPA were strongly correlated (r = 0.828, p = 0.002). TBRs were higher for IMT than IPA (1.95+/-0.50 versus 1.79+/-0.42; p < 0.05), but independent from tumour cell density (p > 0.1). Visual interpretation by different observers was more concordant for IMT-SPECT than IPA-SPECT (kappa 1.0 versus 0.774). No differences in early TBRs were observed between low-grade and high-grade gliomas for IMT (1.97+/-0.53 versus 2.21+/-0.44, p > 0.5) or IPA (1.70+/-0.23 versus 2.21+/-0.56, p = 0.167) with a trend to higher TBRs in low-grade tumours for IMT (p = 0.093). In contrast to the known wash-out of IMT, we observed persistent accumulation of IPA in gliomas. CONCLUSIONS: IPA shows lower TBRs than IMT, especially in low-grade tumours, so IMT should be preferred for the delineation of low-grade gliomas by SPECT imaging. Due to its prolonged retention, however, IPA remains promising for therapeutic use in gliomas after labelling with I-131.