Assessment of left ventricular function with gated myocardial perfusion SPECT and gated myocardial FDG PET in patients with left ventricular mechanical dyssynchrony.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) and left ventricular function are intertwined. Gated myocardial perfusion SPECT (MPS) and gated fluorodeoxyglucose positron emission computed tomography (FDG PET) is an elegant way for repeated assessment of myocardial dyssynchrony and myocardial function. To the knowledge of the authors at the time this manuscript was prepared, there was no comprehensive evaluation of the interplay of LVMD and left ventricular function as measured by gated MPS and gated FDG PET; as well as no evaluation of the agreement between the two methods. METHODS: Patients were assigned to the reference cohort (RC) and the dyssynchrony cohort (DC) based on the phase analysis results of gated MPS datasets. Subsequently left ventricular function was analyzed. RESULTS: We demonstrated that LVMD as detected by gated MPS is associated with a significantly higher end-diastolic volume (EDV) and end-systolic volume (ESV) as well as a significantly reduced left ventricular ejection fraction (LVEF) both in gated MPS and gated FDG PET imaging. In the RC and the DC SPECT and PET showed good agreement and generally high linear correlations with regard to left ventricular volumes and LVEF. In the combined cohort (RC and DC) increasing amounts of LVMD were associated with increasing left ventricular volumes as well as a decreasing LVEF. The association was strongest for the dyssynchrony parameter Entropy. CONCLUSIONS: We demonstrated that gated SPECT and gated PET are useful tools in the evaluation of left ventricular function in patients with LVMD as detected by gated MPS. Increasing amounts of dyssynchrony were associated with an increasingly reduced myocardial function. For repeated measurements or therapy monitoring, the methods should not be used interchangeably.

[68Ga]DOTA-TATE PET for the detection of early transplant rejection in a heterotopic allograft heart transplantation model of the rat: a pilot study.

BACKGROUND: The most important cause of heart transplant loss is early acute allograft rejection, caused by the infiltration of lymphocytes, development of edema and myocardial necrosis. It has been propagated that [68Ga]DOTA-TATE PET might be suitable to quantify the presence of SSTR over-expressing lymphocytes. With heterotopic allogenic heart transplant models in the rat readily available, we aimed to investigate, if monitoring and quantification of acute allograft rejection after heterotopic allogenic heart transplantation was feasible by non-invasive serial [68Ga]DOTA-TATE PET. METHODS: Seventeen Lewis rats (9 for serial PET imaging, 8 for histological correlation) received allogenic heterotopic heart transplants from 17 Brown-Norway rats. On days 4, 6 and 7 a [68Ga]DOTA-TATE PET scan was performed. RESULTS: Imaging of acute transplant rejection until 7 days after allogenic heart transplantation in the rat is feasible. Heterotopic allografts showed significantly increased tracer uptake on day 4 until day 7 after transplantation, reflecting the process of histologically detected myocardial lymphocytic infiltration. Both the area of infarction and the amount of necrosis increased over the course of 7 days, with necrosis reaching statistical significance. CONCLUSIONS: We purport that the detected PET signal is primarily a specific marker of lymphocyte infiltration and only to a lesser extent an unspecific marker of infarction and necrosis. Thus, [68Ga]DOTA-TATE PET might be a suitable tool for serial imaging and quantification of lymphocyte infiltration as a direct mediator of acute allograft rejection at an early stage after heart transplantation.

Outcome after PSMA-PET/CT-based salvage radiotherapy for nodal recurrence after radical prostatectomy.

PURPOSE: Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence. METHODS: A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA < post-RT nadir + 0.2 ng/ml and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method and uni- and multivariate analysis was performed. RESULTS: Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1-40.1) in patients with bcP and 1.4 ng/ml (range 0.3-5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD21.5 Gy of 66 Gy (60-70 Gy) was delivered to the prostatic fossa, 70 Gy (66-72 Gy) to the local recurrence, if present, 65.1 Gy (56-66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4-50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. < 12 months) and LN localization (pelvic vs. paraaortic) were associated with improved BRFS and concomitant ADT and lower PSA value before sRT (< 1 vs. > 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes. CONCLUSIONS: Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome.

68Ga-EMP-100 PET/CT-a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma-first in-human biodistribution and imaging results.

BACKGROUND: 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. METHODS: Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. RESULTS: Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86-29.16)), followed by bone metastases (SUVmax 5.56 (0.97-15.85)), and lymph node metastases (SUVmax 3.90 (2.13-6.28)) and visceral metastases (SUVmax 3.82 (0.11-16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. CONCLUSION: Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients.

The assessment of left ventricular mechanical dyssynchrony from gated 99mTc-tetrofosmin SPECT and gated 18F-FDG PET by QGS: a comparative study.

BACKGROUND: Due to partly conflicting studies, further research is warranted with the QGS software package, with regard to the performance of gated FDG PET phase analysis as compared to gated MPS as well as the establishment of possible cut-off values for FDG PET to define dyssynchrony. METHODS: Gated MPS and gated FDG PET datasets of 93 patients were analyzed with the QGS software. BW, Phase SD, and Entropy were calculated and compared between the methods. The performance of gated PET to identify dyssynchrony was measured against SPECT as reference standard. ROC analysis was performed to identify the best discriminator of dyssynchrony and to define cut-off values. RESULTS: BW and Phase SD differed significantly between the SPECT and PET. There was no significant difference in Entropy with a high linear correlation between methods. There was only moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony with a cut-off point at 62%. CONCLUSION: Gated MPS and gated FDG PET can assess LVMD. The methods cannot be used interchangeably. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. Further prospective research is necessary.

Quantitative myocardial perfusion SPECT/CT for the assessment of myocardial tracer uptake in patients with three-vessel coronary artery disease: Initial experiences and results.

BACKGROUND: To evaluate quantitative myocardial perfusion SPECT/CT datasets for routine clinical reporting and the assessment of myocardial tracer uptake in patients with severe TVCAD. METHODS: MPS scans were reconstructed as quantitative SPECT datasets using CTs from internal (SPECT/CT, Q_INT) and external (PET/CT, Q_EXT) sources for attenuation correction. TPD was calculated and compared to the TPD from non-quantitative SPECT datasets of the same patients. SUVmax, SUVpeak, and SUVmean were compared between Q_INT and Q_EXT SPECT datasets. Global SUVmax and SUVpeak were compared between patients with and without TVCAD. RESULTS: Quantitative reconstruction was feasible. TPD showed an excellent correlation between quantitative and non-quantitative SPECT datasets. SUVmax, SUVpeak, and SUVmean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUVmean differed significantly between the two groups. Global SUVmax and SUVpeak were significantly reduced in patients with TVCAD. CONCLUSIONS: Absolute quantification of myocardial tracer uptake is feasible. The method seems to be robust and principally suitable for routine clinical reporting. Quantitative SPECT might become a valuable tool for the assessment of severe coronary artery disease in a setting of balanced ischemia, where potentially life-threatening conditions might otherwise go undetected.

Apparent diffusion coefficients (ADC) in response assessment of transarterial radioembolization (TARE) for liver metastases of neuroendocrine tumors (NET): a feasibility study.

BACKGROUND: In patients with hepatic neuroendocrine tumors (NETs) locoregional therapies such as transarterial radioembolization (TARE) are increasingly applied. Response evaluation remains challenging and previous studies assessing response with diffusion-weighted imaging (DWI) have been inconclusive. PURPOSE: To perform a feasibility study to evaluate if response assessment with quantitative apparent diffusion coefficient (ADC) in patients with liver metastases of NETs after TARE will be possible. MATERIAL AND METHODS: Retrospectively, 43 patients with 120 target lesions who obtained abdominal magnetic resonance imaging (MRI) with DWI 39±28 days before and 74±46 days after TARE were included. Intralesional ADC (ADCmin, ADCmax, and ADCmean) were measured for a maximum number of three lesions per patient on baseline and post-interventional DWI. Tumor response was categorized according to RECIST 1.1 and mRECIST. RESULTS: TARE resulted in partial remission (PR) in 23% (63%), in stable disease (SD) in 73% (23%), in progressive disease (PD) in 5% (7%) and in complete response (CR) in 0% (1%) according to RECIST 1.1 (mRECIST, respectively). ADC values increased significantly (P<0.005) after TARE in the PR group whereas there was no significant change in the PD group. Post-therapeutic ADC values of SD lesions increased significantly when evaluated by RECIST 1.1 but not if evaluated by mRECIST. Percentual changes of ADCmean values were slightly higher for responders compared to non-responders (P<0.05). CONCLUSION: ADC values seem to represent an additional marker for treatment response evaluation after TARE in patients with secondary hepatic NET. A conclusive study seems feasible though patient-based evaluation and overall survival and progression free survival as alternate primary endpoints should be considered.

[F18] FDG-PET/CT for manual or semiautomated GTV delineation of the primary tumor for radiation therapy planning in patients with esophageal cancer: is it useful?

BACKGROUND: Target volume definition of the primary tumor in esophageal cancer is usually based on computed tomography (CT) supported by endoscopy and/or endoscopic ultrasound and can be difficult given the low soft-tissue contrast of CT resulting in large interobserver variability. We evaluated the value of a dedicated planning [F18] FDG-Positron emission tomography/computer tomography (PET/CT) for harmonization of gross tumor volume (GTV) delineation and the feasibility of semiautomated structures for planning purposes in a large cohort. METHODS: Patients receiving a dedicated planning [F18] FDG-PET/CT (06/2011-03/2016) were included. GTV was delineated on CT and on PET/CT (GTVCT and GTVPET/CT, respectively) by three independent radiation oncologists. Interobserver variability was evaluated by comparison of mean GTV and mean tumor lengths, and via Sørensen-Dice coefficients (DSC) for spatial overlap. Semiautomated volumes were constructed based on PET/CT using fixed standardized uptake values (SUV) thresholds (SUV30, 35, and 40) or background- and metabolically corrected PERCIST-TLG and Schaefer algorithms, and compared to manually delineated volumes. RESULTS: 45 cases were evaluated. Mean GTVCT and GTVPET/CT were 59.2/58.0 ml, 65.4/64.1 ml, and 60.4/59.2 ml for observers A-C. No significant difference between CT- and PET/CT-based delineation was found comparing the mean volumes or lengths. Mean Dice coefficients on CT and PET/CT were 0.79/0.77, 0.81/0.78, and 0.8/0.78 for observer pairs AB, AC, and BC, respectively, with no significant differences. Mean GTV volumes delineated semiautomatically with SUV30/SUV35/SUV40/Schaefer's and PERCIST-TLG threshold were 69.1/23.9/18.8/18.6 and 70.9 ml. The best concordance of a semiautomatically delineated structure with the manually delineated GTVCT/GTVPET/CT was observed for PERCIST-TLG. CONCLUSION: We were not able to show that the integration of PET/CT for GTV delineation of the primary tumor resulted in reduced interobserver variability. The PERCIST-TLG algorithm seemed most promising compared to other thresholds for further evaluation of semiautomated delineation of esophageal cancer.

Value of PET imaging for radiation therapy.

This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.

Clinical impact of follicular oncocytic (Hürthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma.

PURPOSE: There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT). METHODS: We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival. RESULTS: Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0-19.8) vs. 20.1 years (95% CI 19.0-21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309-0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years). CONCLUSIONS: Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.

The impact of the extent of the bone involvement on overall survival and toxicity in mCRPC patients receiving [177Lu]Lu-PSMA-617: a WARMTH multicentre study.

INTRODUCTION: Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. METHODS: The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6-20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. RESULTS: A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia. CONCLUSION: The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.

Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [177Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial).

INTRODUCTION: The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the "617 trial") to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617. MATERIALS AND METHODS: The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. RESULTS: The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. CONCLUSION: In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0-1 is associated with a longer OS.

Dosimetry and optimal scan time of [18F]SiTATE-PET/CT in patients with neuroendocrine tumours.

PURPOSE: Radiolabelled somatostatin analogues targeting somatostatin receptors (SSR) are well established for combined positron emission tomography/computer tomography (PET/CT) imaging of neuroendocrine tumours (NET). [18F]SiTATE has recently been introduced showing high image quality, promising clinical performance and improved logistics compared to the clinical reference standard 68Ga-DOTA-TOC. Here we present the first dosimetry and optimal scan time analysis. METHODS: Eight NET patients received a [18F]SiTATE-PET/CT (250 ± 66 MBq) with repeated emission scans (10, 30, 60, 120, 180 min after injection). Biodistribution in normal organs and SSR-positive tumour uptake were assessed. Dosimetry estimates for risk organs were determined using a combined linear-monoexponential model, and by applying 18F S-values and reference target masses for the ICRP89 adult male or female (OLINDA 2.0). Tumour-to-background ratios were compared quantitatively and visually between different scan times. RESULTS: After 1 h, normal organs showed similar tracer uptake with only negligible changes until 3 h post-injection. In contrast, tracer uptake by tumours increased progressively for almost all types of metastases, thus increasing tumour-to-background ratios over time. Dosimetry resulted in a total effective dose of 0.015 ± 0.004 mSv/MBq. Visual evaluation revealed no clinically relevant discrepancies between later scan times, but image quality was rated highest in 60 and 120 min images. CONCLUSION: [18F]SiTATE-PET/CT in NET shows overall high tumour-to-background ratios from 60 to 180 min after injection and an effective dose comparable to 68Ga-labelled alternatives. For clinical use of [18F]SiTATE, the best compromise between image quality and tumour-to-background contrast is reached at 120 min, followed by 60 min after injection.

The diagnostic challenge of coexistent sarcoidosis and thyroid cancer - a retrospective study.

BACKGROUND: Sarcoid lesions may mimic metastatic disease or recurrence in thyroid cancer (TC) patients as both diseases may affect the lungs and lymph nodes. We present the first study to systematically evaluate the clinical course of patients with (TC) after adjuvant radioactive iodine therapy (RIT) and concomitant sarcoidosis of the lung or the lymph nodes. METHODS: We screened 3285 patients and retrospectively identified 16 patients with TC (11 papillary thyroid cancer (PTC), 3 follicular thyroid cancer (FTC), 1 oncocytic PTC, 1 oncocytic FTC) and coexisting sarcoidosis of the lung and/or the lymph nodes treated at our institute. All patients had undergone thyroidectomy and initial adjuvant RIT. Challenges in diagnosing and the management of these patients were evaluated during long term follow-up (median 4.9 years (0.8-15.0 years)). RESULTS: Median age at first diagnosis of TC was 50.1 years (33.0-71.5 years) and of sarcoidosis 39.4 years (18.0-63.9 years). During follow-up, physicians were able to differentiate between SA and persistent or recurrent TC in 10 of 16 patients (63%). Diagnosis was complicated by initial negative thyroglobulin (Tg), positive Tg antibodies and non-specific imaging findings. Histopathology can reliably distinguish between SA and TC in patients with one suspicious lesion. CONCLUSION: Physicians should be aware of the rare coexistence of sarcoidosis and TC. Lymphadenopathy and pulmonary lesions could be metastases, sarcoidosis or even a mix of both. Therefore, this rare patient group should receive a thorough work up including histopathological clarification and, if necessary, separately for each lesion.

PSMA-positive nodal recurrence in prostate cancer : Salvage radiotherapy is superior to salvage lymph node dissection in retrospective analysis.

PURPOSE: This analysis compares salvage lymph node dissection (SLND) to salvage lymph node radiotherapy (SLNRT) of 68Ga-PSMA PET-positive nodal recurrences after radical prostatectomy (RPE). METHODS: A total of 67 SLNRT and 33 SLND consecutive patients with pelvic and/or para-aortic nodal recurrences after RPE were retrospectively analyzed. Biochemical recurrence-free survival rates (bRFS; PSA <0.2 ng/mL) were calculated according to Kaplan-Meier and survival curves were compared using the log rank test. For multivariable analysis, binary logistic regression analysis was performed (p < 0.05). RESULTS: Median follow-up was 17 months (range, 6-53 months) in SLND patients and 31 months (range, 3-56 months) in SLNRT patients (p = 0.027). SLNRT patients had significantly more tumours of pT3 and pT4 category (82% vs. 67%; p = 0.006), pathologically involved lymph nodes (45% vs. 27%; p = 0.001) and positive surgical margins (54% vs. 12%; p = 0.001) at time of RPE than SLND patients. PSA persistence after RPE was significantly more frequently observed in the SLNRT cohort (73% vs. 27%; p = 0.001). There was no significant difference in the distribution of PET-positive lymph nodes. Median PSA before SLND was higher than before SLNRT (3.07 ng/ml vs. 1.3 ng/ml; p = 0.393). The 2­year bRFS was significantly higher in the SLNRT vs. the SLND cohort (92% vs. 30%; p = 0.001) with lower rates of distant metastases (21% vs. 52%; p = 0.002) and secondary treatments (5% vs. 39%; p = 0.011) irrespective of ongoing androgen deprivation therapy at last contact. In multivariable analysis, SLNRT was significantly associated with prolonged bRFS (regression coefficient 1.436, hazard ratio 4.204, 95% CI 1.789-9.878; p = 0.001). CONCLUSION: Based on this retrospective study SLNRT might be the preferred treatment option for patients with nodal recurrence after previous RPE.

Biodistribution and first clinical results of 18F-SiFAlin-TATE PET: a novel 18F-labeled somatostatin analog for imaging of neuroendocrine tumors.

INTRODUCTION: PET/CT using 68Ga-labeled somatostatin analogs (SSA) targeting somatostatin receptors (SSR) on the cell surface of well-differentiated neuroendocrine tumors (NET) represents the clinical reference standard for imaging. However, economic and logistic challenges of the 68Ge/68Ga generator-based approach have disadvantages over 18F-labeled compounds. Here, we present the first in-human data of 18F-SiFAlin-TATE, a novel 18F-labeled, SSR-targeting peptide. The aim was to compare the intra-individual biodistribution, tumor uptake, and image quality of 18F-SiFAlin-TATE to the clinical reference standard 68Ga-DOTA-TOC. METHODS: Thirteen patients with NET staged with both 68Ga-DOTA-TOC and 18F-SiFAlin-TATE PET/CT have been included in this retrospective analysis. We compared the biodistribution in normal organs and tumor uptake of NET lesions by SUVmean and SUVmax measurement for tracers. Additionally mean and max tumor-to-liver (TLR) and tumor-to-spleen ratios (TSR) have been calculated by division of SUVmean and SUVmax of tumor lesions by the SUVmean of the liver and spleen, respectively. Additionally, image quality was visually rated by 5 blinded readers and an intra-class correlation (ICC) analysis on inter-observer agreement has been performed. RESULTS: Compared with 68Ga-DOTA-TOC, the biodistribution of 18F-SiFAlin-TATE showed somewhat higher, however, statistically not significant higher uptake in the liver, spleen, and adrenal glands. Significantly higher uptake was observed in the kidneys. Tumor uptake was higher in most tumor lesions with significantly higher uptake in common metastatic sites of NET including the liver (SUVmax 18.8 ± 8.4 vs. 12.8 ± 5.6; p < 0.001), lymph nodes (SUVmax 23.8 ± 20.7 vs. 17.4 ± 16.1; p < 0.001) and bone (SUVmax 16.0 ± 10.1 vs. 10.3 ± 5.7; p < 0.01) for 18F-SiFAlin-TATE. The high tumor uptake resulted in favorable TLR and TSR, comparable with that of 68Ga-DOTA-TOC. The ICC analysis on the inter-observer agreement on image quality was substantial and almost perfect. Image quality was rated as excellent in most cases in both 68Ga-DOTA-TOC and 18F-SiFAlin-TATE PET. CONCLUSION: The favorable characteristics of 18F-SiFAlin-TATE with a high image quality, the kit-like labeling procedure, and the promising clinical performance enable improved logistics and diagnostic possibilities for PET imaging of NET. Our first clinical results warrant further systematic studies investigating the clinical use of 18F-SiFAlin-TATE in NET patients.

68Ga-PSMA-11 Positron Emission Tomography Detects Residual Prostate Cancer after Prostatectomy in a Multicenter Retrospective Study.

PURPOSE: Prostate specific antigen persistence after radical prostatectomy is associated with adverse outcomes in patients with prostate cancer. We sought to define regions at risk for residual disease as well as the accuracy of prostate specific membrane antigen ligand positron emission tomography in patients with prostate specific antigen persistence. MATERIALS AND METHODS: At 6 participating centers a total of 191 patients who underwent 68Ga-prostate specific membrane antigen-11 positron emission tomography/computerized tomography or positron emission tomography/magnetic resonance imaging for persistently elevated postoperative prostate specific antigen (0.1 ng/ml or greater) were retrospectively included in study. The detection rate and the positive predictive value were determined. In 33 patients with additional prostate specific membrane antigen ligand positron emission tomography before prostatectomy we also determined the rate of positron emission tomography based persistence and recurrence. RESULTS: Prostate specific membrane antigen ligand positron emission tomography localized prostate cancer in 130 of 191 patients (68%) with prostate specific antigen persistence at a median prostate specific antigen of 1.1 ng/ml. The detection rate significantly increased with prostate specific antigen (p <0.001). Regarding prostate specific membrane antigen positron emission tomography/computerized tomography only 61 of 173 patients (35%) had disease confined to the pelvis while 57 of 173 (33%) had distant lesions. The most frequently affected nodal regions were the obturator in 42% and the presacral/mesorectal region in 40%. In 15 of the 33 patients (45%) with prostate specific membrane antigen ligand positron emission tomography before and after surgery at least 1 lesion was detected at baseline (positron emission tomography persistence), 8 (24%) had new lesions (positron emission tomography recurrence) and 10 (30%) had negative positron emission tomography findings. The positive predictive value of prostate specific membrane antigen ligand positron emission tomography was 91%. Systemic therapy initiation was significantly associated with distant lesions on prostate specific membrane antigen ligand positron emission tomography. CONCLUSIONS: Prostate specific membrane antigen ligand positron emission tomography localized prostate cancer in more than two-thirds of patients with high risk features and prostate specific antigen persistence after prostatectomy. Obturator and presacral/mesorectal nodes are at high risk for persistent metastasis.

Long-term outcome of rare oncocytic papillary (Hürthle cell) thyroid carcinoma following (adjuvant) initial radioiodine therapy.

PURPOSE: Oncocytic (Hürthle cell) papillary thyroid carcinoma (OPTC) is a rare variant of the papillary thyroid carcinoma (PTC) which comprises approximately 1 to 11 % of PTC cases. Its clinical course and prognosis have not been comprehensively documented and the clinical outcome remains a controversial issue. Therefore, we investigated the long-term prognosis after thyroidectomy and (adjuvant) initial radioactive iodine therapy (RIT) of OPTC compared to PTC. METHODS: A total of 563 patients (47 with OPTC and 516 with PTC) with a median follow-up of 9.9 (0.3; 23.5) years were studied. All patients underwent thyroidectomy followed by (adjuvant) initial RIT. Data on the patients' demographics, pathology, laboratory findings, imaging studies, treatment, and follow-up including recurrence, and disease-specific survival were collected. Cox's multivariate regression model was used to identify independent prognostic factors for survival. RESULTS: OPTC patients were significantly older (55.2 ± 12.3 years) than PTC patients (50.3 ± 13.5) at the time of initial diagnosis (p value 0.016). Initial tumor size was larger in the OPTC group (2.8 ± 1.8 cm for OPTC patients, 1.5 ± 1.2 cm for PTC patients, p value < 0.001). Before matching, OPTC patients presented more often with evidence of disease at the last visit of follow-up (p value 0.046). However, this difference was not observed anymore after matching for risk factors (p value 0.637). Disease-specific survival did not differ significantly. Age (HR, 1.183; 95% CI, 1.097-1.276) was identified as an independent prognostic factor for disease-specific survival. OPTC patients predominantly showed a recurrence of distant metastasis within a shorter time despite being not statistically significant. CONCLUSION: At initial diagnosis, OPTC shows significant differences in terms of age and initial tumor size compared to PTC. Patients suffering from OPTC present with the same clinical long-term outcome indifferent to PTC after (adjuvant) initial RIT after matching.

Practical recommendations for radium-223 treatment of metastatic castration-resistant prostate cancer.

PURPOSE: Radium Ra 223 dichloride (radium-223, Xofigo®) is the first targeted alpha therapy for patients with castration-resistant prostate cancer and symptomatic bone metastases. Radium-223 provides a new treatment option for this setting, but also necessitates a new treatment management approach. We provide straightforward and practical recommendations for European nuclear medicine centres to optimize radium-223 service provision. METHODS: An independent research consultancy agency observed radium-223 procedures and conducted interviews with all key staff members involved in radium-223 treatment delivery in 11 nuclear medicine centres across six countries (Germany, Italy, the Netherlands, Spain, Switzerland and the UK) experienced in administering radium-223. The findings were collated and discussed at a meeting of experts from these centres, during which key consensus recommendations were defined. RESULTS: The recommendations cover centre organization and preparation; patient referral; radium-223 ordering, preparation and disposal; radium-223 treatment delivery/administration; and patient experience. Guidance includes structured coordination and communication within centres and multidisciplinary teams, focusing on sharing best practice to provide high-quality, patient-centred care throughout the treatment pathway. CONCLUSIONS: These expert recommendations are intended to complement existing management guidelines. Sharing best practice and experience will help nuclear medicine centres to optimize radium-223 service provision and improve patient care.