Diagnostic accuracy of intraoperative perfusion-weighted MRI and 5-aminolevulinic acid in relation to contrast-enhanced intraoperative MRI and 11C-methionine positron emission tomography in resection of glioblastoma: a prospective study.

The aim of our study was to compare depicted pre-, intra-, and postoperative tumor volume of met-PET, perfusion-weighed MRI (PWI), and Gd-DTPA MRI. Further, to assess their sensitivity and specificity in correlation with histopathological specimen. Inclusion criteria of the prospective study were histological confirmed glioblastoma (GB), age > 18, and eligible for gross total resection (GTR). Met-PET was performed before and after surgery. Gd-DTPA MRI and PWI were performed before, during, and after surgery. A combined 5-aminolevulinic acid (5-ALA) and iMRI-guided surgery was performed. Volumetric analysis was evaluated for all imaging modalities except for 5-ALA. A total of 59 navigated biopsies were taken. Sensitivity and specificity were calculated for Gd-DTPA MRI, PWI, met-PET, and 5-ALA according to the histology of specimen. Met-PET depicted significantly larger tumor volume before surgery (p = 0.01) compared to PWI and Gd-DTPI MRI. We found no significant difference in tumor volume between met-PET and PWI after surgery (p = 0.059). Both PWI and met-PET showed significantly larger tumor volume after surgery when compared to Gd-DTPA (p = 0.018 and p = 0.003, respectively). Intraoperative PWI reading was impaired in 33.3% due to artifacts. Met-PET showed the highest sensitivity for detection of GB with 95%. The lowest sensitivity was found with Gd-DTPA MRI (50%), while 5-ALA and intraoperative PWI showed similar results (69 and 67%). Met-Pet is the imaging modality with the highest sensitivity to detect a residual tumor in GB. Intraoperative PWI seems to have a synergistic effect to Gd-DTPA and 5-ALA. However, its value may be limited by artifacts. Both pre- and intraoperative PWI cannot substitute met-PET in tumor detection.

Radiofluorination of PSMA-HBED via Al(18)F(2+) Chelation and Biological Evaluations In Vitro.

PURPOSE: Ga-68-labeled prostate-specific membrane antigen (PSMA) ligands have been used clinically for positron emission tomography (PET) imaging of prostate cancer. However, F-18-labeled compounds offer several advantages, including the potential for delayed imaging, high starting activities enabling multidose preparation, and improved spatial resolution in PET. For F-18 labeling of peptides conjugated with a suitable chelator, a fast and feasible method is the use of [Al(18)F](2+). In the present study, the radiofluorinations of a well-known PSMA ligand Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (PSMA-HBED) via [Al(18)F](2+) were performed with respect to various reaction parameters, along with the biological evaluations in a cell experiment. PROCEDURES: [Al(18)F]PSMA-HBED was prepared by adding Na[(18)F]F into a vial containing 0.026 µmol peptide (in 0.05 M NaOAc buffer) and 0.03 µmol AlCl3⋅6H2O (in 0.05 M NaOAc buffer). Then, it was stirred at different temperatures from 1 to 30 min. Afterwards, purification was carried out by solid phase extraction. Biological evaluations were performed in PSMA-positive cell lines LNCaP C4-2, along with a negative control using PC-3 cell lines. RESULTS: The best labeling results (81 ± 0.5 %, n = 4) were observed with 0.026 µmol peptide (30 °C, 5 min). For preclinical experiments, the production of [Al(18)F]PSMA-HBED at 35 °C including purification by solid phase extraction (SPE) succeeded within 45 min, resulting in a radiochemical yield of 49 ± 1.2 % (decay-corrected, n = 6, radiochemical purity ≥98 %) at EOS. The labeled peptide revealed serum stability for 4 h as well as a promising binding coefficient (K D) value of 10.3 ± 2.2 nM in cell experiments with PSMA-positive LNCaP C4-2 cells. CONCLUSION: An efficient and one-pot method for the radiosynthesis of [Al(18)F]PSMA-HBED was developed (0.26 µmol of precursor at 35 °C). In cell culture studies, the K D suggests [Al(18)F]PSMA-HBED as a potential PSMA ligand for future investigations in vivo and clinical applications afterwards.

Synthesis, Radiolabelling and In Vitro Characterization of the Gallium-68-, Yttrium-90- and Lutetium-177-Labelled PSMA Ligand, CHX-A''-DTPA-DUPA-Pep.

Since prostate-specific membrane antigen (PSMA) has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET) showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, KD values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively) and resulted in nearly quantitative radiochemical yields within 5 min.

Detection of lymph node metastasis in patients with nodal prostate cancer relapse using (18)F/(11)C-choline positron emission tomography/computerized tomography.

PURPOSE: We evaluated the diagnostic accuracy of choline positron emission tomography/computerized tomography for nodal relapse of prostate cancer according to topographical site and tumor infiltration size in lymph nodes. MATERIALS AND METHODS: A total of 72 patients with nodal prostate cancer relapse after primary therapy underwent pelvic and/or retroperitoneal salvage lymph node dissection. Salvage was done after whole body positron emission tomography/computerized tomography with (11)C-choline or (18)F-fluoroethylcholine showed positron emission tomography positive lymph nodes but no other detectable metastasis. Diagnostic accuracy was evaluated in 160 dissected lymph node regions (pelvic left/right and retroperitoneal), 498 subregions (common, external and internal iliac, obturator, presacral, aortic bifurcation, aortal, vena caval and interaortocaval) and 2,122 lymph nodes. RESULTS: Lymph node metastasis was present in 32% of resected lymph nodes (681 of 2,122), resulting in 238 positive subregions and 111 positive regions. Positron emission tomography/computerized tomography was positive for 110 regions and 209 subregions. Sensitivity, specificity, positive and negative predictive values, and accuracy were 91.9%, 83.7%, 92.7%, 82.0% and 89.4% (region based), 80.7%, 93.5%, 91.9%, 84.1% and 87.3% (subregion based), and 57.0%, 98.4%, 94.5%, 82.6% and 84.9% (lesion based), respectively. Of 393 positive lymph node metastases detected by this method 278 (70.7%) were in lymph nodes with a less than 10 mm short axis diameter. Imaging sensitivity was 13.3%, 57.4% and 82.8% for a tumor infiltration depth of 2 or greater to less than 3 mm, 5 or greater to less than 6 mm and 10 or greater to less than 11 mm, respectively. Lymph node metastasis site and the radiotracer ((11)C-choline/(18)F-fluoroethylcholine) had no substantial impact on diagnostic accuracy. CONCLUSIONS: Choline positron emission tomography/computerized tomography detects affected lymph node regions (pelvic left/right and retroperitoneal) in patients with prostate cancer relapse with high accuracy and it seems helpful for guiding salvage lymph node dissection. Sensitivity decreases with the size of metastatic infiltration in lymph nodes. This technique detects metastasis in a significant fraction of lymph nodes that are not pathologically enlarged on computerized tomography.

Accurate preoperative localization of parathyroid adenomas with C-11 methionine PET/CT.

BACKGROUND: Focused unilateral or minimally invasive parathyroidectomy for primary hyperparathyroidism (pHPT) depends on the successful preoperative localization of parathyroid adenomas. The aim of this prospective study was to determine the accuracy of C-11 methionine positron emission tomography/computed tomography (Met-PET/CT), a novel localization procedure for hyperfunctional parathyroid tissue. METHODS: Preoperative Met-PET/CT scans of the neck and mediastinum of 102 patients undergoing parathyroidectomy for pHPT were preoperatively evaluated by a radiologist and a nuclear medicine physician and prospectively documented. The results of Met-PET/CT were compared with intraoperative and histopathological findings. RESULTS: pHPT was caused by a single-gland adenoma in 97 patients, whereas 5 patients had multiglandular disease. Met-PET/CT correctly located a single-gland adenoma in 83 of 97 (86%) patients with pHPT (sensitivity 91%). The positive predictive value of Met-PET/CT in localizing a single-gland adenoma was 93%. Of the 5 patients with multiglandular disease, Met-PET/CT identified 2 hyperfunctioning parathyroid glands in 1 patient, 1 gland in 3 individuals, and was negative in the fifth patient (sensitivity 80%). A highly significant correlation was observed between true-positive findings and the size (mean = 1.81 ± 0.84 cm) and weight (mean = 1.50 ± 2.56 g) of parathyroid adenoma, whereas patients with false-negative findings had significantly smaller (mean = 1.09 ± 0.41 cm) and lighter (mean = 0.37 ± 0.29 g) glands (P < 0.001 and P = 0.001, respectively). CONCLUSIONS: This study demonstrates the high accuracy of Met-PET/CT in the preoperative localization of parathyroid adenomas in a large series of patients with pHPT.

Differences in predicted and actually absorbed doses in peptide receptor radionuclide therapy.

PURPOSE: An important assumption in dosimetry prior to radionuclide therapy is the equivalence of pretherapeutic and therapeutic biodistribution. In this study the authors investigate if this assumption is justified in sst2-receptor targeting peptide therapy, as unequal amounts of peptide and different peptides for pretherapeutic measurements and therapy are commonly used. METHODS: Physiologically based pharmacokinetic models were developed. Gamma camera and serum measurements of ten patients with metastasizing neuroendocrine tumors were conducted using (111)In-DTPAOC. The most suitable model was selected using the corrected Akaike information criterion. Based on that model and the estimated individual parameters, predicted and measured (90)Y-DOTATATE excretions during therapy were compared. The residence times for the pretherapeutic (measured) and therapeutic scenarios (simulated) were calculated. RESULTS: Predicted and measured therapeutic excretion differed in three patients by 10%, 31%, and 7%. The measured pretherapeutic and therapeutic excretion differed by 53%, 56%, and 52%. The simulated therapeutic residence times of kidney and tumor were 3.1 ± 0.6 and 2.5 ± 1.2 fold higher than the measured pretherapeutic ones. CONCLUSIONS: To avoid the introduction of unnecessary inaccuracy in dosimetry, using the same substance along with the same amount for pretherapeutic measurements and therapy is recommended.

Value of PET/CT and MR lymphography in treatment of prostate cancer patients with lymph node metastases.

PURPOSE: To determine the clinical value of two novel molecular imaging techniques: (11)C-choline positron emission tomography (PET)/computed tomography (CT) and ferumoxtran-10 enhanced magnetic resonance imaging (magnetic resonance lymphography [MRL]) for lymph node (LN) treatment in prostate cancer (PCa) patients. Therefore, we evaluated the ability of PET/CT and MRL to assess the number, size, and location of LN metastases in patients with primary or recurrent PCa. METHODS AND MATERIALS: A total of 29 patients underwent MRL and PET/CT for LN evaluation. The MRL and PET/CT data were analyzed independently. The number, size, and location of the LN metastases were determined. The location was described as within or outside the standard clinical target volume for elective pelvic irradiation as defined by the Radiation Therapy Oncology Group. Subsequently, the results from MRL and PET/CT were compared. RESULTS: Of the 738 LNs visible on MRL, 151 were positive in 23 of 29 patients. Of the 132 LNs visible on PET/CT, 34 were positive in 13 of 29 patients. MRL detected significantly more positive LNs (p < 0.001) in more patients than PET/CT (p = 0.002). The mean diameter of the detected suspicious LNs on MRL was significantly smaller than those detected by PET/CT, 4.9 mm and 8.4 mm, respectively (p < 0.0001). In 14 (61%) of 23 patients, suspicious LNs were found outside the clinical target volume with MRL and in 4 (31%) of 13 patients with PET/CT. CONCLUSION: In patients with PCa, both molecular imaging techniques, MRL and (11)C-choline PET/CT, can detect LNs suspicious for metastasis, irrespective of the existing size and shape criteria for CT and conventional magnetic resonance imaging. On MRL and PET/CT, 61% and 31% of the suspicious LNs were located outside the conventional clinical target volume. Therefore, these techniques could help to individualize treatment selection and enable image-guided radiotherapy for patients with PCa LN metastases.

Auger electron emitter against multiple myeloma--targeted endo-radio-therapy with 125I-labeled thymidine analogue 5-iodo-4'-thio-2'-deoxyuridine.

INTRODUCTION: Multiple myeloma (MM) is a plasma cell malignancy characterized by accumulation of malignant, terminally differentiated B cells in the bone marrow. Despite advances in therapy, MM remains an incurable disease. Novel therapeutic approaches are, therefore, urgently needed. Auger electron-emitting radiopharmaceuticals are attractive for targeted nano-irradiation therapy, given that DNA of malignant cells is selectively addressed. Here we evaluated the antimyeloma potential of the Auger electron-emitting thymidine analogue (125)I-labeled 5-iodo-4'-thio-2'-deoxyuridine ([(125)I]ITdU). METHODS: Cellular uptake and DNA incorporation of [(125)I]ITdU were determined in fluorodeoxyuridine-pretreated KMS12BM, U266, dexamethasone-sensitive MM1.S and -resistant MM1.R cell lines. The effect of stimulation with interleukin 6 (IL6) or insulin-like growth factor 1 (IGF1) on the intracellular incorporation of [(125)I]ITdU was investigated in cytokine-sensitive MM1.S and MM1.R cell lines. Apoptotic cells were identified using Annexin V. Cleavage of caspase 3 and PARP was visualized by Western blot. DNA fragmentation was investigated using laddering assay. Therapeutic efficiency of [(125)I]ITdU was proven by clonogenic assay. RESULTS: [(125)I]ITdU was shown to be efficiently incorporated into DNA of malignant cells, providing a promising mechanism for delivering highly toxic Auger radiation emitters into tumor DNA. [(125)I]ITdU had a potent antimyeloma effect in cell lines representing distinct disease stages and, importantly, in cell lines sensitive or resistant to the conventional therapeutic agent, but was not toxic for normal plasma and bone marrow stromal cells. Furthermore, [(125)I]ITdU abrogated the protective actions of IL6 and IGF1 on MM cells. [(125)I]ITdU induced massive damage in the DNA of malignant plasma cells, which resulted in efficient inhibition of clonogenic growth. CONCLUSION: These studies may provide a novel treatment strategy for overcoming resistance to conventional therapy in multiple myeloma.

New molecular markers for prostate tumor imaging: a study on 2-methylene substituted fatty acids as new AMACR inhibitors.

The development of prostate carcinoma is associated with alterations in fatty acid metabolism. α-Methylacyl-CoA racemase (AMACR) is a peroxisomal and mitochondrial enzyme that catalyses interconversion between the (S)/(R)-isomers of a range of α-methylacyl-CoA thioesters. AMACR is involved in the ß-oxidation of the dietary branched-chain fatty acids and bile acid intermediates. It is highly expressed in prostate (more than 95 %), colon (92 %), and breast cancers (44 %) but not in the respective normal or hyperplastic tissues. Thus, targeting of AMACR could be a new strategy for molecular imaging and therapy of prostate and some other cancers. Unlabeled 2-methylenacyl-CoA thioesters (12 a-c) were designed as AMACR binding ligands. The thioesters were tested for their ability to inhibit the AMACR-mediated epimerization of (25R)-THC-CoA and were found to be strong AMACR inhibitors. Radioiodinated (E)-(131) I-13-iodo-2-methylentridec-12-enoic acid ((131) I-7 c) demonstrated preferential retention in AMACR-positive prostate tumor cells (LNCaP, LNCaP C4-2wt and DU145) compared with both AMACR-knockout LNCaP C4-2 AMACR-siRNA and benign BPH1 prostate cell lines. A significant protein-bound radioactive fraction with main bands at 47 (sum of molecular weights of AMACR plus 12 c), 70, and 75 kDa was detected in LNCaP C4-2 wt cells. In contrast, only negligible amounts of protein-bound radioactivity were found in LNCaP C4-2 AMACR-siRNA cells.

Optimal preloading in radioimmunotherapy with anti-cD45 antibody.

PURPOSE: Anti-CD45 antibody is predominantly used in the treatment of acute leukemia. CD45 is stably expressed on all leukocytes and their precursors, and therefore the liver and spleen constitute major antigen sinks. Thus, as the red marrow is the target organ, in radioimmunotherapy with anti-CD45 antibody, preloading with unlabeled antibody is a method to increase the absorbed dose to the target cells. In a previous study, a method to individually determine the optimal preload for five patients with acute leukemia was developed. Here, this method is examined and improved using two pretherapeutic measurement series and a refined pharmacokinetic model. METHODS: To obtain the biodistribution of 111In-labeled anti-CD45 antibody under different saturation conditions, two measurement series one with and one without preloading were conducted in five patients. For each patient, two physiologically based pharmacokinetic models were fitted to the data and the corrected Akaike information criterion was used to identify the model, which was empirically most supported. The resultant parameter values were compared to values reported in the literature. To individually determine the optimal amount of unlabeled antibody for therapy, computer simulations for preloads ranging from 0 to 60 mg were performed based on the estimated parameters of each patient. The prediction power of the model was assessed by comparing the simulated therapeutic serum curves to the actual 90Y measurements. RESULTS: Visual inspection showed good fits and the adjusted R2 was >0.90 for all patients. All parameters were in a physiologically reasonable range. The relative deviation of the predicted area under the therapeutic serum curve and the measured curve was 15%-33%. The optimal preloading increased the marrow-over-liver selectivity up to 3.9 fold compared to the simulated biodistribution using a standard dose (0.5 mg/kg). CONCLUSIONS: The presented method can be used to individually determine the optimal preload and the corresponding residence times in radioimmunotherapy with anti-CD45 antibody.

Dependence of the anti-CD66 antibody biodistribution on the dissociation constant: a simulation study.

In radioimmunotherapy (RIT) with radiolabelled anti-CD66 antibody, the red bone marrow is selectively irradiated. A preceding study, employing a physiologically based pharmacokinetic model, has shown that currently about 50% of the anti-CD66 antibody is accumulated in the red marrow. In this work, the potential improvement of the biodistribution is quantified for other anti-CD66 antibodies with lower dissociation constants K(D). Biodistribution simulations were performed based on a recently published mathematical model for a 10- and 100-fold lower monovalent K(D). The therapeutic index was compared to the therapeutic index which is achieved using the actual antibody. The simulations indicate that a considerably increased therapeutic index can be obtained by decreasing the dissociation constant.A reduction of the K(D) to 10-fold or 100-fold lower values would lead to an improvement of the therapeutic index, by a factor of 2.4-5 and 2.4-6.5 respectively. To investigate the predicted improvement of the radioimmunotherapy, new anti-CD66 antibodies with lower dissociation constants should be developed.

Radiosynthesis of a new PSMA targeting ligand ([18F]FPy-DUPA-Pep).

Due to the specificity of expression of PSMA (prostate specific membrane antigen) particularly in prostate cancer cells (e.g. LNCaP), numerous PSMA ligands have been synthesized until now. In the current study, we synthesized DUPA-Pep having 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA) linked via 8-aminooctanoic acid to two phenylalanine residues and chose 6-[(18)F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester [(18)F]FPy-TFP as a prosthetic group for coupling. [(18)F]FPy-DUPA-Pep was obtained in a radiochemical yield of 48±0.9% (decay uncorrected) within 50 min with a chemical purity of >98%.

Radioimmunotherapy-based conditioning for hematopoietic cell transplantation in children with malignant and nonmalignant diseases.

Targeted irradiation of the bone marrow with radiolabeled monoclonal antibodies (radioimmunotherapy) represents a novel therapeutic approach with both myeloablative and antileukemic potential. In an open-label, single-center pilot study, 30 pediatric and adolescent patients undergoing hematopoietic cell transplantation for malignant (n = 16) and nonmalignant (n = 14) disorders received treatment with a 9°Y-labeled anti-CD66 monoclonal antibody. Patients with a high risk of relapse (n = 7) received additional treatment with standard conditioning based on either total body irradiation or busulfan to intensify the antileukemic effect. In patients with comorbidities (n = 23), radioimmunotherapy was combined with a reduced-intensity conditioning regimen to reduce systemic toxicity. Preferential irradiation of the bone marrow was achieved in all patients. Nonrelapse mortality was 4 (13%) of 30 patients. In patients with malignant diseases, the probabilities of overall and disease-free survival at 2 years were 0.69 (95% confidence interval 0.37-0.87) and 0.46 (95% confidence interval 0.19-0.70), respectively. In patients with nonmalignant diseases, the probability of both overall and disease-free survival at 2 years was 0.94 (95% confidence interval 0.63-0.99). This pilot study demonstrates that radioimmunotherapy is effective in achieving myeloablation with low additional toxicity when used in combination with standard or reduced-intensity conditioning in young patients.

The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer.

CONTEXT: Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management. OBJECTIVE: To critically analyse the current evidence for the use of choline PET/CT scanning in the management of patients with a progressive increase in PSA after radical treatment for PCa, evaluating its diagnostic accuracy in the detection of recurrences, the clinical predictors of positive PET/CT examinations, and the modalities' role as a guide for tailored therapeutic strategies. EVIDENCE ACQUISITION: Data on recently published (2003-2010) original articles, review articles, and editorials concerning the role of choline PET/CT in this scenario were analysed. EVIDENCE SYNTHESIS: The diagnostic accuracy of choline PET in detecting sites of PCa relapse has been investigated by several authors, and the overall reported sensitivity ranges between 38% and 98%. It has been demonstrated that choline PET technology's positive detection rate improves with increasing PSA values. The routine use of choline PET/CT cannot be recommended for PSA values <1 ng/ml. However, in addition to PSA serum value, PSA doubling time (PSA DT), and other clinical and pathologic features-including locally advanced tumour (pT3b-T4) or lymph node involvement at initial staging-should be considered to refer patients to choline PET/CT study. Choline PET/CT may be also proposed as a image guide either for experimental surgical or radiation therapy treatments. CONCLUSIONS: According to the current available data, choline PET/CT plays a role in the management of biochemical relapse. Its accuracy is correlated to PSA value, PSA DT, and other pathologic features. Choline PET/CT may be proposed as a guide for individualised treatment of recurrence.

Analysing saturable antibody binding based on serum data and pharmacokinetic modelling.

In radioimmunotherapy, organ dose calculations are frequently based on pretherapeutic biodistribution measurements, assuming equivalence between pretherapeutic and therapeutic biodistribution. However, when saturation of antibody binding sites is important, this assumption might not be justified. Residual antibody and different amounts of administered antibody may lead to a considerably altered therapeutic biodistribution. In this study we developed a method based on serum activity measurements to investigate this effect in radioimmunotherapy with (90)Y-labelled anti-CD66 antibody. Pretherapeutic and therapeutic serum activity data of ten patients with acute leukaemia were fitted to a set of four parsimonious pharmacokinetic models. All models included the key mechanisms of antibody binding, immunoreactivity and degradation; however, they differed with respect to linear or nonlinear binding and global or individual fitting of the model parameters. The empirically most supported model was chosen according to the corrected Akaike information criterion. The nonlinear models were most supported by the data (sum of probabilities approximately 100%). Using the presented method, we identified relevant saturable binding for radioimmunotherapy with (90)Y-labelled anti-CD66 antibody solely based on serum data. This general method may also be applicable to investigate other systems where saturation of binding sites might be important.

Cost-effectiveness of hybrid PET/CT for staging of non-small cell lung cancer.

UNLABELLED: Although the diagnostic effectiveness of integrated PET/CT for staging of non-small cell lung cancer (NSCLC) has already been proven, it remains to be determined if tumor staging with combined metabolic and anatomic imaging is also cost-effective. The objective of this study was to evaluate from a payers' perspective the cost-effectiveness of staging NSCLC with CT alone (representing the mainstay diagnostic test) and with integrated PET/CT. METHODS: The study is based on 172 NSCLC patients from a prospective clinical study who underwent diagnostic, contrast-enhanced helical CT and integrated PET/CT. Imaging was performed at the University Hospital Ulm between May 2002 and December 2004. To calculate treatment costs, we differentiated among cost for diagnosis, cost for nonsurgical treatment according to the clinical diagnosis, and cost for surgical procedures according to the clinical tumor stage. RESULTS: The diagnostic effectiveness in terms of correct TNM staging was 40% (31/77) for CT alone and 60% (46/77) for PET/CT. For the assessment of resectability (tumor stages Ia-IIIa vs. IIIb-IV), 65 of 77 patients (84%) were staged correctly by PET/CT (CT alone, 70% [54/77]). The incremental cost-effectiveness ratios per correctly staged patient were $3,508 for PET/CT versus CT alone. The incremental cost-effectiveness ratios per quality-adjusted life year gained were $79,878 for PET/CT vs. CT alone, decreasing to $69,563 assuming a reduced loss of utility (0.10 quality-adjusted life years) due to surgical morbidity. CONCLUSION: Cost-effectiveness analyses showed that costs for PET/CT are within the commonly accepted range for diagnostic tests or therapies. Therefore, reimbursement of PET/CT for NSCLC staging can be also recommended from an economic point of view.

131I/123I-metaiodobenzylguanidine (mIBG) scintigraphy: procedure guidelines for tumour imaging.

The aim of this document is to provide general information about mIBG scintigraphy in cancer patients. The guidelines describe the mIBG scintigraphy protocol currently used in clinical routine, but do not include all existing procedures for neuroendocrine tumours. The guidelines should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary from one country to another and from one medical institution to another. The present guidelines have been prepared for nuclear medicine physicians and intend to offer assistance in optimizing the diagnostic information that can currently be obtained from mIBG scintigraphy. The corresponding guidelines of the Society of Nuclear Medicine (SNM) and the Dosimetry, Therapy and Paediatric Committee of the EANM have been taken into consideration, and partially integrated into this text. The same has been done with the most relevant literature on this topic, and the final result has been discussed within a group of distinguished experts.

Potential of optimal preloading in anti-CD20 antibody radioimmunotherapy: an investigation based on pharmacokinetic modeling.

Recently, it has been suggested that the concept of preloading is limited by using a standard amount of unlabeled antibody. To identify the potential of optimal preloading, a pharmacokinetic model that describes the biodistribution of anti-CD20 antibody was developed. Simulations were conducted for different tumor burdens, spleen sizes, and tumor permeabilities. The optimal amount of unlabeled antibody was determined for each scenario. These simulations show that the currently administered standard amount is not optimal. A preload of 150 mg or lower would result in equal or higher tumor uptake in all cases. For tumors with high permeability, the uptake of labeled antibody could be increased by a factor of 8.5 using the considerably reduced optimal preload. The most sensitive parameter for the choice of the optimal amount of unlabeled antibody is the tumor uptake index. The results indicate that a personalized approach for radioimmunotherapy (RIT) with anti-CD20 antibody is required to account for the interpatient variability. The optimal amount of unlabeled antibody, which has to be determined by using a pharmacokinetic model, could substantially improve tumor uptake and thus RIT with anti-CD20 antibody.

Clinical value of 18-fluorine-fluorodihydroxyphenylalanine positron emission tomography/computed tomography in the follow-up of medullary thyroid carcinoma.

BACKGROUND: 18-Fluorine-fluorodihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET) is a sensitive method for detecting medullary thyroid carcinoma (MTC). The advent of PET/computed tomography (CT) has enabled more sensitive and specific lesion identification using various tracers in many other tumors. The aim of this study was therefore to test the hypothesis that combined (18)F-DOPA PET/CT more accurately detects MTC lesions than each modality does alone. METHODS: Twenty-eight consecutive (18)F-DOPA PET, CT, and (18)F-DOPA PET/CT scans of patients followed up for sporadic MTC or multiple endocrine neoplasia 2 syndrome-associated MTC were reviewed retrospectively in randomized sequence by two blinded readers, one a nuclear medicine physician and the other a radiologist, with extensive experience interpreting such images. RESULTS: Of 18 lesions detected concurrently by the three modalities, PET identified all as positive for MTC, but was unable to definitively localize 4 (22%) lesions. CT could definitively localize all 18 lesions, but could not definitively diagnose or exclude MTC in 6 (33%) lesions. Further, CT falsely identified as MTC-negative one lesion that was judged to be MTC-positive by both PET and PET/CT. Only PET/CT scans accurately characterized and localized all 18 lesions. On a per patient basis, the sensitivity of (18)F-DOPA PET/CT for MTC was 74% and the specificity, 100%. In the present series, no truly MTC-positive (18)F-DOPA PET/CT case was found in patients with basal human calcitonin (hCt) levels under 60 pg/mL, and conversely, no truly MTC-negative PET/CT case was found in patients with basal hCt over 120 pg/mL. Between hCt concentrations of 60 and 150 pg/mL true-negative, false-negative, and true-positive scans all were obtained. (18)F-DOPA PET/CT had 100% sensitivity and specificity when hCt at the time of scanning was over 150 pg/mL, the threshold at which the 2009 American Thyroid Association guidelines recommend performing additional imaging including (18)F-DOPA PET/CT. CONCLUSIONS: (18)F-DOPA PET/CT allows for a more accurate diagnosis and localization of MTC lesions than do (18)F-DOPA PET or CT alone. Supporting the recent American Thyroid Association recommendations on additional imaging in MTC, (18)F-DOPA PET/CT appears to have 100% sensitivity in patients with hCt over 150 pg/mL.