Salivary Gland Toxicity of PSMA-Targeted Radioligand Therapy with 177Lu-PSMA and Combined 225Ac- and 177Lu-Labeled PSMA Ligands (TANDEM-PRLT) in Advanced Prostate Cancer: A Single-Center Systematic Investigation.

Purpose: PSMA-targeted radioligand therapy (PRLT) is a promising treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, a high uptake of the radiopharmaceutical in the salivary glands (SG) can lead to xerostomia and becomes dose-limiting for 225Ac-PSMA-617. This study investigated the sialotoxicity of 177Lu-PSMA-I&T/-617 monotherapy and co-administered 225Ac-PSMA-617 and 177Lu-PSMA-617 (Tandem-PPRLT). Methods: Three patient cohorts, that had undergone 177Lu-PSMA-I&T/-617 monotherapy or Tandem-PRLT, were retrospectively analyzed. In a short-term cohort (91 patients), a xerostomia assessment (CTCAE v.5.0), a standardized questionnaire (sXI), salivary gland scintigraphy (SGS), and SG SUVmax and the metabolic volume (MV) on 68Ga-PSMA-11-PET/CT were obtained before and after two cycles of 177Lu-PSMA-I&T/-617. In a long-term cohort, 40 patients were similarly examined. In a Tandem cohort, the same protocol was applied to 18 patients after one cycle of Tandem-PRLT. Results: Grade 1 xerostomia in the short-term follow-up was observed in 22 (24.2%) patients with a worsening of sXI from 7 to 8 at (p < 0.05). In the long-term cohort, xerostomia grades 1 to 2 occurred in 16 (40%) patients. SGS showed no significant changes, but there was a decline of the MV of all SGs. After Tandem-PRLT, 12/18 (66.7%) patients reported xerostomia grades 1 to 2, and the sXI significantly worsened from 9.5 to 14.0 (p = 0.005), with a significant reduction in the excretion fraction (EF) and MV of all SGs. Conclusion: 177Lu-PSMA-I&T/-617 causes only minor SG toxicity, while one cycle of Tandem-PRLT results in a significant SG impairment. This standardized protocol may help to objectify and quantify SG dysfunction.

Relationship between age at initiation of cysteamine treatment, adherence with therapy, and glomerular kidney function in infantile nephropathic cystinosis.

Infantile nephropathic cystinosis, due to impaired transport of cystine out of lysosomes, occurs with an incidence of 1 in 100-200,000 live births. It is characterized by renal Fanconi syndrome in the first year of life and glomerular dysfunction progression to end-stage kidney disease by approximately 10 years of age. Treatment with oral cysteamine therapy helps preserve glomerular function, but affected individuals eventually require kidney replacement therapy. This is because glomerular damage had already occurred by the time a child is diagnosed with cystinosis, typically in the second year of life. We performed a retrospective multicenter study to investigate the impact of initiating cysteamine treatment within the first 2 months of life in some infants and comparing two different levels of adherence in patients diagnosed at the typical age. We collected 3983 data points from 55 patients born between 1997 and 2020; 52 patients with 1592 data points could be further evaluated. These data were first analyzed by dividing the patient cohort into three groups: (i) standard treatment start with good adherence, (ii) standard treatment start with less good adherence, and (iii) early treatment start. At every age, mean estimated glomerular filtration rate (eGFR) was higher in early-treated patients than in later-treated patients. Second, a generalized additive mixed model (GAMM) was applied showing that patients with initiation of treatment before 2 months of age are expected to have a 34 ml/min/1.73 m2 higher eGFR than patients with later treatment start while controlling for adherence and patients' age. These data strongly suggest that oral cysteamine treatment initiated within 2 months of birth preserves kidney function in infantile nephropathic cystinosis and provide evidence of the utility of newborn screening for this disease.

Feasibility, Biodistribution, and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy of Diverse Adenocarcinomas Using 177Lu-FAP-2286: First-in-Humans Results.

Fibroblast activation protein (FAP) is a promising target for diagnosis and therapy of numerous malignant tumors. FAP-2286 is the conjugate of a FAP-binding peptide, which can be labeled with radionuclides for theranostic applications. We present the first-in-humans results using 177Lu-FAP-2286 for peptide-targeted radionuclide therapy (PTRT). Methods: PTRT using 177Lu-FAP-2286 was performed on 11 patients with advanced adenocarcinomas of the pancreas, breast, rectum, or ovary after prior confirmation of uptake on 68Ga-FAP-2286 or 68Ga-FAPI-04 PET/CT. Results: Administration of 177Lu-FAP-2286 (5.8 ± 2.0 GBq; range, 2.4-9.9 GBq) was well tolerated, with no adverse symptoms or clinically detectable pharmacologic effects being noticed or reported in any of the patients. The whole-body effective dose was 0.07 ± 0.02 Gy/GBq (range, 0.04-0.1 Gy/GBq). The mean absorbed doses for kidneys and red marrow were 1.0 ± 0.6 Gy/GBq (range, 0.4-2.0 Gy/GBq) and 0.05 ± 0.02 Gy/GBq (range, 0.03-0.09 Gy/GBq), respectively. Significant uptake and long tumor retention of 177Lu-FAP-2286 resulted in high absorbed tumor doses, such as 3.0 ± 2.7 Gy/GBq (range, 0.5-10.6 Gy/GBq) in bone metastases. No grade 4 adverse events were observed. Grade 3 events occurred in 3 patients-1 with pancytopenia, 1 with leukocytopenia, and 1 with pain flare-up; 3 patients reported a pain response. Conclusion:177Lu-FAP-2286 PTRT, applied in a broad spectrum of cancers, was relatively well tolerated, with acceptable side effects, and demonstrated long retention of the radiopeptide. Prospective clinical studies are warranted.

The influence of radio frequency ablation on intra-articular fluid temperature in the ankle joint - a cadaver study.

BACKGROUND: Radio frequency ablation devices have found a widespread application in arthroscopic surgery. However, recent publications report about elevated temperatures, which may cause damage to the capsular tissue and especially to chondrocytes. The purpose of this study was the investigation of the maximum temperatures that occur in the ankle joint with the use of a commercially available radio frequency ablation device. METHODS: Six formalin-fixed cadaver ankle specimens were used for this study. The radio frequency device was applied for 120 s to remove tissue. Intra-articular temperatures were logged every second for 120 s at a distance of 3, 5 and 10 mm from the tip of the radio frequency device. The irrigation fluid flow was controlled by setting the inflow pressure to 10 mmHg, 25 mmHg, 50 mmHg and 100 mmHg, respectively. The controller unit voltage setting was set to 1, 5 and 9. RESULTS: Maximum temperatures exceeding 50 °C/122 °F were observed for all combinations of parameters, except for those with a pressure of 100 mmHg pressure. The main critical variable is the pressure setting, which is highly significant. The controller unit voltage setting showed no effect on the temperature measurements. The highest temperature was 102.7 °C/215.6 °F measured for an irrigation flow of 10 mmHg. The shortest time span to exceed 50 °C/122 °F was 3 s. CONCLUSION: In order to avoid temperatures exceeding 50 °C/122 °F in the use of radio frequency devices in arthroscopic surgeries of the ankle joint, it is recommended to use a high irrigation flow by setting the pressure difference across the ankle joint as high as feasible. Even short intervals of a low irrigation flow may lead to critical temperatures above 50 °C/122 °F. LEVEL OF EVIDENCE: Level II, diagnostic study.

Theranostics of prostate cancer: from molecular imaging to precision molecular radiotherapy targeting the prostate specific membrane antigen.

Alterations at the molecular level are a hallmark of cancer. Prostate cancer is associated with the overexpression of prostate-specific membrane antigen (PSMA) in a majority of cases, predominantly in advanced tumors, increasing with the grade or Gleason's score. PSMA can be selectively targeted using radiolabeled PSMA ligands. These small molecules binding the PSMA can be radiolabeled with γ-emitters like 99mTc and 111In or positron emitters like 68Ga and 18F for diagnosis as well as with their theranostic pairs such as 177Lu (ß-emitter) or 225Ac (α-emitter) for therapy. This review summarizes the theranostic role of PSMA ligands for molecular imaging and targeted molecular radiotherapy, moving towards precision oncology.

Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms.

INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing neuroendocrine neoplasms has shown promising results in clinical trials and a recently published phase III study. METHODS: In our center, 2294 patients were screened between 2004 and 2014 by 68Ga somatostatin receptor (SSTR) PET/CT. Intention to treat analysis included 1048 patients, who received at least one cycle of 90Yttrium or 177Lutetium-based PRRT. Progression free survival was determined by 68Ga SSTR-PET/CT and EORTC response criteria. Adverse events were determined by CTCAE criteria. RESULTS: Overall survival (95% confidence interval) of all patients was 51 months (47.0-54.9) and differed significantly according to radionuclide, grading, previous therapies, primary site and functionality. Progression free survival (based on PET/CT) of all patients was 19 months (16.9-21), which was significantly influenced by radionuclide, grading, and origin of neuroendocrine neoplasm. Progression free survival after initial progression and first and second resumption of PRRT after therapy-free intervals of more than 6 months were 11 months (9.4-12.5) and 8 months (6.4-9.5), respectively. Myelodysplastic syndrome or leukemia developed in 22 patients (2.1%) and 5 patients required hemodialysis after treatment, other adverse events were rare. CONCLUSION: PRRT is effective and overall survival is favorable in patients with neuroendocrine neoplasms depending on the radionuclide used for therapy, grading and origin of the neuroendocrine neoplasm which is not exactly mirrored in progression free survival as determined by highly sensitive 68Ga somatostatin receptor PET/CT using EORTC criteria for determining response to therapy.

Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: systematic review and meta-analysis.

Objective To assess the effect of specialist palliative care on quality of life and additional outcomes relevant to patients in those with advanced illness.Design Systematic review with meta-analysis.Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and trial registers searched up to July 2016.Eligibility criteria for selecting studies Randomised controlled trials with adult inpatients or outpatients treated in hospital, hospice, or community settings with any advanced illness. Minimum requirements for specialist palliative care included the multiprofessional team approach. Two reviewers independently screened and extracted data, assessed the risk of bias (Cochrane risk of bias tool), and evaluated the quality of evidence (GRADE tool).Data synthesis Primary outcome was quality of life with Hedges' g as standardised mean difference (SMD) and random effects model in meta-analysis. In addition, the pooled SMDs of the analyses of quality of life were re-expressed on the global health/QoL scale (item 29 and 30, respectively) of the European Organization for Research and Treatment of Cancer QLQ-C30 (0-100, high values=good quality of life, minimal clinically important difference 8.1).Results Of 3967 publications, 12 were included (10 randomised controlled trials with 2454 patients randomised, of whom 72% (n=1766) had cancer). In no trial was integration of specialist palliative care triggered according to patients' needs as identified by screening. Overall, there was a small effect in favour of specialist palliative care (SMD 0.16, 95% confidence interval 0.01 to 0.31; QLQ-C30 global health/QoL 4.1, 0.3 to 8.2; n=1218, six trials). Sensitivity analysis showed an SMD of 0.57 (-0.02 to 1.15; global health/QoL 14.6, -0.5 to 29.4; n=1385, seven trials). The effect was marginally larger for patients with cancer (0.20, 0.01 to 0.38; global health/QoL 5.1, 0.3 to 9.7; n=828, five trials) and especially for those who received specialist palliative care early (0.33, 0.05 to 0.61, global health/QoL 8.5, 1.3 to 15.6; n=388, two trials). The results for pain and other secondary outcomes were inconclusive. Some methodological problems (such as lack of blinding) reduced the strength of the evidence.Conclusions Specialist palliative care was associated with a small effect on QoL and might have most pronounced effects for patients with cancer who received such care early. It could be most effective if it is provided early and if it identifies though screening those patients with unmet needs.Systematic review registration PROSPERO CRD42015020674.

Improved image quality with simultaneously reduced radiation exposure: Knowledge-based iterative model reconstruction algorithms for coronary CT angiography in a clinical setting.

BACKGROUND: The aim of this study was to assess the potential for radiation dose reduction using knowledge-based iterative model reconstruction (K-IMR) algorithms in combination with ultra-low dose body mass index (BMI)-adapted protocols in coronary CT angiography (coronary CTA). METHODS: Forty patients undergoing clinically indicated coronary CTA were randomly assigned to two groups with BMI-adapted (I: <25.0 kg/m2, II: <28.0 kg/m2, III: <30.0 kg/m2, IV: ≥30.0 kg/m2) low dose (LD, I: 100kVp/75 mAs, II: 100kVp/100 mAs, III: 100kVp/150 mAs, IV: 120kVp/150 mAs, n = 20) or ultra-low dose (ULD, I: 100kVp/50 mAs, II: 100kVp/75 mAs, III: 100kVp/100 mAs, IV: 120kVp/100 mAs, n = 20) protocols. Prospectively-triggered coronary CTA was performed using a 256-MDCT with the lowest reasonable scan length. Images were generated with filtered back projection (FBP), a noise-reducing hybrid iterative algorithm (iD, levels 2/5) and K-IMR using cardiac routine (CR) and cardiac sharp settings, levels 1-3. RESULTS: Groups were comparable regarding anthropometric parameters, heart rate, and scan length. The use of ULD protocols resulted in a significant reduction of radiation exposure (0.7 (0.6-0.9) mSv vs. 1.1 (0.9-1.7) mSv; p < 0.02). Image quality was significantly better in the ULD group using K-IMR CR 1 compared to FBP, iD 2 and iD 5 in the LD group, resulting in fewer non-diagnostic coronary segments (2.4% vs. 11.6%, 9.2% and 6.1%; p < 0.05). CONCLUSIONS: The combination of K-IMR with BMI-adapted ULD protocols results in significant radiation dose savings while simultaneously improving image quality compared to LD protocols with FBP or hybrid iterative algorithms. Therefore, K-IMR allows for coronary CTA examinations with high diagnostic value and very low radiation exposure in clinical routine.

Radiolabeling of DOTA-like conjugated peptides with generator-produced (68)Ga and using NaCl-based cationic elution method.

Gallium-68 ((68)Ga) is a generator-produced radionuclide with a short half-life (t½ = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize (68)Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging. By working in a lead-shielded hot-cell system,(68)Ga(3+) of the generator eluate is trapped on a cation exchanger cartridge (100 mg, ∼8 mm long and 5 mm diameter) and then eluted with acidified 5 M NaCl solution directly into a sodium acetate-buffered solution containing a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or DOTA-like chelator-modified peptide. The main advantages of this procedure are the high efficiency and the absence of organic solvents. It can be applied to a variety of peptides, which are stable in 1 M NaCl solution at a pH value of 3-4 during reaction. After labeling, neutralization, sterile filtration and quality control (instant thin-layer chromatography (iTLC), HPLC and pH), the radiopharmaceutical can be directly administered to patients, without determination of organic solvents, which reduces the overall synthesis-to-release time. This procedure has been adapted easily to automated synthesis modules, which leads to a rapid preparation of (68)Ga radiopharmaceuticals (12-16 min).

177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy.

UNLABELLED: The objective of this study was to analyze the safety and efficacy of the (177)Lu-labeled DOTAGA-based prostate-specific membrane antigen (PSMA) ligand (177)Lu-DOTAGA-(I-y)fk(Sub-KuE) ((177)Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Fifty-six mCRPC patients underwent PSMA radioligand therapy (RLT) with (177)Lu-PSMA. (68)Ga-PSMA-(N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid) ((68)Ga-PSMA) PET/CT was used for patient selection and follow-up after PSMA RLT. Hematologic status, renal function, and serum prostate-specific antigen levels were documented before and after therapy. Dosimetry was performed in 30 patients. RESULTS: (177)Lu-PSMA demonstrated high absorbed tumor doses (median, 3.3 mGy/MBq) compared with the levels in normal organs. Parotid glands received higher doses (1.3 mGy/MBq) than kidneys (0.8 mGy/MBq). All patients tolerated the therapy without any acute adverse effects. Except for mild reversible xerostomia in 2 patients, no long-term side effects were observed. There was a small but statistically significant reduction in erythrocyte and leukocyte counts; only the reduction in erythrocyte counts decreased slightly below the reference range. No thrombocytopenia occurred. The severity of pain was significantly reduced in 2 of 6 patients (33.3%). A decrease in prostate-specific antigen levels was noted in 45 of 56 patients (80.4%). Of 25 patients monitored for at least 6 mo after 2 or more PSMA RLT cycles, a molecular response evaluation ((68)Ga-PSMA PET/CT) revealed partial remission in 14, stable disease in 2, and progressive disease in 9 patients. Contrast-enhanced CT revealed partial remission in 5, stable disease in 13, and progressive disease in 7 patients. The median progression-free survival was 13.7 mo, and the median overall survival was not reached during follow-up for 28 mo. CONCLUSION: PSMA RLT with (177)Lu-PSMA is feasible, safe, and effective in end-stage progressive mCRPC with appropriate selection and follow-up of patients by (68)Ga-PSMA PET/CT through application of the concept of theranostics.

Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [68Ga]SB3 and PET/CT.

PURPOSE: Gastrin-releasing peptide receptors (GRPR) represent attractive targets for tumor diagnosis and therapy because of their overexpression in major human cancers. Internalizing GRPR agonists were initially proposed for prolonged lesion retention, but a shift of paradigm to GRPR antagonists has recently been made. Surprisingly, radioantagonists, such as [(99m)Tc]DB1 ((99m)Tc-N4'-DPhe(6),Leu-NHEt(13)]BBN(6-13)), displayed better pharmacokinetics than radioagonists, in addition to their higher inherent biosafety. We introduce here [(68)Ga]SB3, a [(99m)Tc]DB1 mimic-carrying, instead of the (99m)Tc-binding tetraamine, the chelator DOTA for labeling with the PET radiometal (68)Ga. METHODS: Competition binding assays of SB3 and [(nat)Ga]SB3 were conducted against [(125)I-Tyr(4)]BBN in PC-3 cell membranes. Blood samples collected 5 min postinjection (pi) of the [(67)Ga]SB3 surrogate in mice were analyzed using high-performance liquid chromatography (HPLC) for degradation products. Likewise, biodistribution was performed after injection of [(67)Ga]SB3 (37 kBq, 100 µL, 10 pmol peptide) in severe combined immunodeficiency (SCID) mice bearing PC-3 xenografts. Eventually, [(68)Ga]SB3 (283 ± 91 MBq, 23 ± 7 nmol) was injected into 17 patients with breast (8) and prostate (9) cancer. All patients had disseminated disease and had received previous therapies. PET/CT fusion images were acquired 60-115 min pi. RESULTS: SB3 and [(nat)Ga]SB3 bound to the human GRPR with high affinity (IC50: 4.6 ± 0.5 nM and 1.5 ± 0.3 nM, respectively). [(67)Ga]SB3 displayed good in vivo stability (>85 % intact at 5 min pi). [(67)Ga]SB3 showed high, GRPR-specific and prolonged retention in PC-3 xenografts (33.1 ± 3.9%ID/g at 1 h pi - 27.0 ± 0.9%ID/g at 24 h pi), but much faster clearance from the GRPR-rich pancreas (≈160%ID/g at 1 h pi to <17%ID/g at 24 h pi) in mice. In patients, [(68)Ga]SB3 elicited no adverse effects and clearly visualized cancer lesions. Thus, 4 out of 8 (50 %) breast cancer and 5 out of 9 (55 %) prostate cancer patients showed pathological uptake on PET/CT with [(68)Ga]SB3. CONCLUSION: [(67)Ga]SB3 showed excellent pharmacokinetics in PC-3 tumor-bearing mice, while [(68)Ga]SB3 PET/CT visualized lesions in about 50 % of patients with advanced and metastasized prostate and breast cancer. We expect imaging with [(68)Ga]SB3 to be superior in patients with primary breast or prostate cancer.

Magnetic resonance perfusion and diffusion imaging characteristics of transient bone marrow edema, avascular necrosis and subchondral insufficiency fractures of the proximal femur.

PURPOSE: To evaluate magnetic resonance (MR) perfusion and diffusion imaging characteristics in patients with transient bone marrow edema (TBME), avascular necrosis (AVN), or subchondral insufficiency fractures (SIF) of the proximal femur. MATERIALS AND METHODS: 29 patients with painful hip and bone marrow edema pattern of the proximal femur on non-contrast MR imaging were examined using diffusion-weighted and dynamic gadolinium-enhanced sequences. Apparent diffusion coefficients (ADCs) and perfusion parameters were calculated for different regions of the proximal femur. Regional distribution and differences in ADC values and perfusion parameters were evaluated. RESULTS: Seven patients presented with TBME, 15 with AVN and seven with SIF of the proximal femur. Perfusion imaging showed significant differences for maximum enhancement values (Emax), slope (Eslope) and time to peak (TTP) between the three patient groups (p<0.05). In contrast, no significant differences for ADC values were calculated when comparing TBME, AVN, and SIF patients. CONCLUSION: Diffusion weighted imaging of bone marrow of the proximal femur did not show significant differences between patients with TBME, AVN or SIF. In contrast, MR perfusion imaging demonstrated significant differences for the different patient groups and may as a complementary imaging technique add information to the understanding of the pathophysiology of diseases associated with bone marrow edema.

Purification and labeling strategies for (68)Ga from (68)Ge/ (68)Ga generator eluate.

For successful labeling, (68)Ge/(68)Ga generator eluate has to be concentrated (from 10 mL or more to less than 1 mL) and to be purified of metallic impurities, especially Fe(III), and (68)Ge breakthrough. Anionic, cationic and fractional elution methods are well known. We describe two new methods: (1) a combined cationic-anionic purification and (2) an easy-to-use and reliable cationic purification with NaCl solution. Using the first method, (68)Ga from 10 mL generator eluate was collected on a SCX cartridge, then eluted with 1.0 mL 5.5 M HCl directly on an anion exchanger (30 mg AG1X8). After drying with a stream of helium, (68)Ga was eluted with 0.4 mL water into the reaction vial. We provide as an example labeling of BPAMD. Using the second method, (68)Ga from 10 mL generator eluate was collected on a SCX cartridge, then eluted with a hydrochloric solution of sodium chloride (0.5 mL 5 M NaCl, 12.5 µL 5.5 M HCl) into the reaction vial, containing 40 µg DOTATOC and 0.5 mL 1 M ammonium acetate buffer pH 4.5. After heating for 7 min at 90°C, the reaction was finished. Radiochemical purity was higher than 95% without further purification. No (68)Ge breakthrough was found in the final product.

Simplified NaCl based (68)Ga concentration and labeling procedure for rapid synthesis of (68)Ga radiopharmaceuticals in high radiochemical purity.

A simple sodium chloride (NaCl) based (68)Ga eluate concentration and labeling method that enables rapid, high-efficiency labeling of DOTA conjugated peptides in high radiochemical purity is described. The method utilizes relatively few reagents and comprises minimal procedural steps. It is particularly well-suited for routine automated synthesis of clinical radiopharmaceuticals. For the (68)Ga generator eluate concentration step, commercially available cation-exchange cartridges and (68)Ga generators were used. The (68)Ga generator eluate was collected by use of a strong cation exchange cartridge. 98% of the total activity of (68)Ga was then eluted from the cation exchange cartridge with 0.5 mL of 5 M NaCl solution containing a small amount of 5.5 M HCl. After buffering with ammonium acetate, the eluate was used directly for radiolabeling of DOTATOC and DOTATATE. The (68)Ga-labeled peptides were obtained in higher radiochemical purity compared to other commonly used procedures, with radiochemical yields greater than 80%. The presence of (68)Ge could not be detected in the final product. The new method obviates the need for organic solvents, which eliminates the required quality control of the final product by gas chromatography, thereby reducing postsynthesis analytical effort significantly. The (68)Ga-labeled products were used directly, with no subsequent purification steps, such as solid-phase extraction. The NaCl method was further evaluated using an automated fluid handling system and it routinely facilitates radiochemical yields in excess of 65% in less than 15 min, with radiochemical purity consistently greater than 99% for the preparation of (68)Ga-DOTATOC.

Reduction of radiation exposure and improvement of image quality with BMI-adapted prospective cardiac computed tomography and iterative reconstruction.

PURPOSE: To assess the impact of body mass index (BMI)-adapted protocols and iterative reconstruction algorithms (iDose) on patient radiation exposure and image quality in patients undergoing prospective ECG-triggered 256-slice coronary computed tomography angiography (CCTA). METHODS: Image quality and radiation exposure were systematically analyzed in 100 patients. 60 Patients underwent prospective ECG-triggered CCTA using a non-tailored protocol and served as a 'control' group (Group 1: 120 kV, 200 mAs). 40 Consecutive patients with suspected coronary artery disease (CAD) underwent prospective CCTA, using BMI-adapted tube voltage and standard (Group 2: 100/120 kV, 100-200 mAs) versus reduced tube current (Group 3: 100/120 kV, 75-150 mAs). Iterative reconstructions were provided with different iDose levels and were compared to filtered back projection (FBP) reconstructions. Image quality was assessed in consensus of 2 experienced observers and using a 5-grade scale (1=best to 5=worse), and signal- and contrast-to-noise ratios (SNR and CNR) were quantified. RESULTS: CCTA was performed without adverse events in all patients (n=100, heart rate of 47-87 bpm and BMI of 19-38 kg/m2). Patients examined using the non-tailored protocol in Group 1 had the highest radiation exposure (3.2±0.4 mSv), followed by Group 2 (1.7±0.7 mSv) and Group 3 (1.2±0.6 mSv) (radiation savings of 47% and 63%, respectively, p<0.001). Iterative reconstructions provided increased SNR and CNR, particularly when higher iDose level 5 was applied with Multi-Frequency reconstruction (iDose5 MFR) (14.1±4.6 versus 21.2±7.3 for SNR and 12.0±4.2 versus 18.1±6.6 for CNR, for FBP versus iDose5 MFR, respectively, p<0.001). The combination of BMI adaptation with iterative reconstruction reduced radiation exposure and simultaneously improved image quality (subjective image quality of 1.4±0.4 versus 1.9±0.5 for Group 2 reconstructed using iDose5 MFR versus Group 1 reconstructed using FBP, p<0.05). CONCLUSIONS: Prospective ECG-triggered 256-slice CCTA allows for visualization of the coronary artery tree with high image quality within a wide range of heart rates and BMIs. The combination of BMI-adapted protocols with iterative reconstruction algorithms can reduce radiation exposure for the patients and simultaneously improve image quality.

Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine based on a cartridge purification method.

INTRODUCTION: O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is widely used as a positron emission tomography tracer for brain tumors. Usually, a high-performance liquid chromatography (HPLC) purification at the end of the two-step synthesis is applied. In this work, we report an automatic radiosynthesis of FET with a purification procedure based on standard cartridges. METHODS: O-(2-[(18)F]fluoroethyl)-L-tyrosine was prepared by [(18)F]fluoroethylation of L-tyrosine by a two-step synthesis using a modified [(11)C]methionine module (Nuclear Interface). In the first reaction step, we synthesized [(18)F]fluoroethyltosylate starting from [(18)F]fluoride. After a purification step, L-tyrosine was [(18)F]fluoroethylated with [(18)F]fluoroethyltosylate. The final reaction mixture was purified by means of solid phase extraction. The FET was trapped on an SCX cartridge, eluted with saline solution and trapped again on an HRX cartridge. For a second purification step, the FET was eluted from the HRX cartridge with ammonium acetate buffer and collected on two SCX cartridges followed by a washing step with water. The final product was eluted with saline solution and neutralised with 450 µl NaHCO(3) solution (8.4%). RESULTS: The synthesis was finished after 50 min and delivered the FET in a range of 3-16 GBq. The synthesis typically yielded 41% (21 experiments) of FET (d.c.) without an HPLC purification step. The radiochemical purity ranged between 97% and 100%. CONCLUSION: We present a radiosynthesis of FET where the usually used HPLC purification procedure has been substituted by a purification step based on standard cartridges. This method is useful for automatic modules without an expensive HPLC purification unit and for the routine production of FET.

Determinants of troponin release in patients with stable coronary artery disease: insights from CT angiography characteristics of atherosclerotic plaque.

OBJECTIVE: To understand the determinants of troponin release in patients with stable coronary artery disease (CAD) by comparing high sensitive troponin T (hsTnT) levels with computed tomography angiography (CTA) characteristics of atherosclerotic plaque. METHODS: hsTnT was determined in 124 consecutive patients with stable angina, who underwent clinically indicated 256-slice CTA for suspected CAD. CTA was used to assess (1) coronary calcification; (2) stenosis severity; (3) non-calcified plaque volume; (4) plaque composition (soft or mixed, described as 'non-calcified' versus calcified) and (5) the presence of vascular remodeling in areas of non-calcified plaque. RESULTS: All CT scans were performed without adverse events, and diagnostic image quality was achieved in 1830/1848 available coronary segments (99.0%). In 29/124 patients, hsTnT was ≥14 pg/ml (range 14.0-34.4). Weak, albeit significant, correlations were found between hsTnT and calcium scoring (r=0.45, p<0.001), while a stronger correlation was found between hsTnT and the total non-calcified plaque burden (r=0.79, p<0.001). Patients with non-calcified plaque (n=44) yielded significantly higher hsTnT values than those with normal vessels (n=46) or those with only calcified lesions (n=26), (12.6 ± 5.2 vs 8.3 ± 2.6 and 8.8 ± 3.0 pg/ml, respectively, p<0.001). Furthermore, those with remodeled non-calcified plaque (n=8) showed even higher hsTnT values of 26.3 ± 6.5 pg/ml than all other groups (p<0.001). This allowed the identification of patients with remodeled non-calcified plaque by hsTnT with high accuracy (area under the curve=0.90, SE=0.07, 95% CI 0.84 to 0.95). CONCLUSIONS: Chronic clinically silent rupture of non-calcified plaque with subsequent microembolisation may be a potential source of troponin elevation. In light of recent imaging studies, in which patients with positively remodeled non-calcified plaque were shown to be at high risk for developing acute coronary syndromes, hsTnT may serve as a biomarker for such 'vulnerable' coronary lesions even in presumably stable CAD.

Comparison of skin adhesive and absorbable intracutaneous suture for the implantation of cardiac rhythm devices.

AIMS: Wound healing is a major determent in the post-surgical course of patients (pts) after pacemaker (PM) and implantable cardioverter defibrillator (ICD) implantation. Insufficient closure may lead to serious complications with pocket infections leading to the device's explantation as the worst case scenario. In addition to the different types of suture and suture clips, a novel topical skin adhesive containing 2-octyl-cyanoacrylate is commercially available. METHODS AND RESULTS: Over a period of 18 months, we prospectively assigned all cases of PM, ICD, and loop recorder implants either to skin adhesive (Group 1) or to absorbable intracutaneous polydioxanon suture (Group 2). Data were analysed with respect to operation time, wound infections, and healing disorders. One hundred and eighty-three pts were randomized into Group 1 [71 PMs, 60 ICD, 15 cardiac resynchronization therapy (CRT), 11 loop recorders, and 26 generator replacements]. One hundred and eighty-five pts were assigned to Group 2 (62 PMs, 70 ICD, 30 CRT, 7 loop recorders, and 16 generator replacements). There were no differences regarding sex, diabetes, renal insufficiency, corticosteroid therapy, oral anticoagulants, and acetylsalicylic asa/clopidogrel (P = n.s.). For the significantly higher amount of CRT devices (P < 0.05) in Group 2, the procedure times are given for surgeries except CRT. It was 49.1 ± 27.7 min for Group 1 and 53.4 ± 31.9 min for Group 2 (P = n.s.). Adverse events as insufficient closure, major and minor bleeding, pocket haematoma, erythema, incrustation, dehiscence, keloid, and explantation due to infection occurred significantly more often in the adhesive group (P = 0.02). The greatest impact on this result had early adverse events as insufficient closure, wound incrustation, and inflammation (9.3 vs. 6.0%; P = 0.02). We did not find any difference in long-term adverse events, infections in particular (2.7 vs. 1.6%; P = 0.47). CONCLUSION: This study shows no benefit using skin adhesive in comparison to absorbable intracutaneous suture regarding surgery times for the implantation of cardiac rhythm devices. The rate of early adverse events after wound closure is higher after skin adhesive but no difference in long-term adverse events occurred.

Phantom-less QCT BMD system as screening tool for osteoporosis without additional radiation.

PURPOSE: Phantom-less bone mineral density (PLBMD) systems are easily integrated into the CT workflow for non-dedicated Quantitative CT (QCT) BMD measurements in thoracic and abdominal scans. This in vivo retrospective study aims to determine accuracy and precision of the PLBMD option located on the Extended Brilliance Workspace (Philips Medical Systems, Cleveland, OH, US) from both cross-sectional and longitudinal image data. MATERIALS AND METHODS: The cross-sectional comparison with phantom-based QCT BMD was performed for 82 patients (61 female, 21 male) with a mean age of (63.0±11.8 SD) years on 197 vertebrae. This was followed by an interobserver variability analysis on 71 vertebrae. The longitudinal PLBMD study was carried out on 45 vertebrae from 10 patients (5 female, 5 male) with a mean age of (64.4±11.5 SD) years. They were re-scanned with standardized scan and contrast-injection protocols within a mean and median of (33±41 SD) and 8 days, respectively. All CT scans were acquired on an Mx8000 Quad (Philips) at Florence-Nightingale Hospital, Kaiserswerth, Germany, in a spiral acquisition mode. RESULTS: A negligible BMD bias of -0.9mg/cm(3) for the PLBMD option was observed with respect to phantom-based QCT BMD. Applying CT number matching of muscle and fat ROIs, the analysis of cross-sectional interobserver and of longitudinal variability yielded precision values of 3.1mg/cm(3) (CV%=4.0) and 4.2mg/cm(3) (CV%=5.3), respectively. CONCLUSION: Although the precision is inferior to phantom-based BMD systems, PLBMD is a robust clinical utility for the detection of lowered BMD in a large patient population. This can be achieved without additional radiation exposure from non-contrasted CT scans, to perform an ancillary diagnosis of osteopenia or osteoporosis.

Cost-effectiveness of using clinical risk factors with and without DXA for osteoporosis screening in postmenopausal women.

BACKGROUND: According to several guidelines, the assessment of postmenopausal fracture risk should be based on clinical risk factors (CRFs) and bone density. Because measurement of bone density by dual x-ray absorptiometry (DXA) is quite expensive, there has been increasing interest to estimate fracture risk by CRFs. OBJECTIVE: The aim of this study was to determine the cost-effectiveness of osteoporosis screening of CRFs with and without DXA compared with no screening in postmenopausal women in Germany. METHODS: A cost-utility analysis and a budget-impact analysis were performed from the perspective of the statutory health insurance. A Markov model simulated costs and benefits discounted at 3% over lifetime. RESULTS: Cost-effectiveness of CRFs compared with no screening is euro4607, euro21,181, and euro10,171 per quality-adjusted life-year (QALY) for 60-, 70-, and 80-year-old women, respectively. Cost-effectiveness of DXA plus CRFs compared with CRFs alone is euro20,235 for 60-year-old women. In women above the age of 70, DXA plus CRFs dominates CRFs alone. DXA plus CRFs results in annual costs of euro175 million, or 0.4% of the statutory health insurance's annual budget. CONCLUSION: Funders should be careful in adopting a strategy based on CRFs alone instead of DXA plus CRFs. Only if DXA is not available, assessing CRFs only is an acceptable option in predicting a woman's risk of fracture.