Patient-Orientated Evaluation of Treatment of Non-Melanoma Skin Cancer with Rhenium-188 Compared to Surgery.

BACKGROUND: Non-melanoma skin cancers (NMSCs) are responsible for up to one-third of all human malignancies. Surgery is usually the treatment of choice, but patients often experience pain during the procedure. Topical rhenium-188 resin skin cancer treatment (RSCT) may be a valid therapeutic alternative. METHODS: In this monocentric pilot study, 19 patients suffering from NMSC were treated with RSCT. Most of these patients had also experienced surgery, either because they developed a new NMSC in aftercare, or they had suffered previously from NMSC. Three RSCT-treated patients, who had no exposure to surgery so far, were paired with three matched patients, who had received surgery. We sought to evaluate and compare the patients' experience with both treatments. A questionnaire assessed patients' perceptions regarding side effects, aesthetic outcomes, wound care, fear of complications, and personal treatment preferences. Patients evaluated the different parameters of their either RSCT- or surgery-treated lesions on a scale from 0-10. RESULTS: Patients were more afraid of complications before surgery than before RSCT (p = 0.04). Treatment with RSCT caused significantly less pain on treatment day (mean 0.56) than surgery (mean 2.32) (0 no pain, 10 maximum pain) (p = 0.02) and 14 days after the procedure (mean 0.89 versus mean 2.47) (p = 0.02). On day 14, RSCT-treated lesions were also significantly less itchy (mean 0.34) than after surgery (mean 1.50). Most patients were very satisfied with the aesthetic outcome after both RSCT (mean 8.42) and surgery (mean 8.31) (p = 0.89). In the case of a new NMSC, the majority of patients who experienced both treatments would rather be treated primarily with RSCT (44%) or would consider both options (31%); only 19% preferred surgery. CONCLUSION: Patients evaluated RSCT as less painful than surgery. The aesthetic outcomes of both treatments were comparable. For pain-sensitive patients, RSCT might be a preferable treatment option.

Impact of 68Ga-PSMA PET/CT on radiation treatment planning of prostate cancer patients.

AIM: This study aimed to assess the impact of 68Ga-PSMA PET/CT on radiation treatment (RT) planning in prostate cancer patients with salvage (sRT) or definitive (dRT) radiotherapy. METHODS: 38 patients (27 sRT, median PSA 0.79 ng/ml (range 0.06-12.1); 11 dRT, median PSA 4.35 ng/ml (range 1.55-55.5) underwent 68Ga-PSMA PET/CT before RT. Influence of 68Ga-PSMA PET/CT on the extent of planning target volume (PTV) and addition of PET-based boosts were assessed. Median follow up was 12 months (range 3-24). RESULTS: 68Ga-PSMA PET/CT showed positive findings in 23/38 patients (8/23: local recurrence (LR), 11/23: nodal metastasis, 1/23: LR and nodal, 2/23: solitary bone metastasis, 1/23: oligometastatic nodal/ bone metastases). In sRT primary PTV was changed in 16/27 patients extending the PTV to the lymphatic drainage (10/16), PSMA-positive LR (3/16), bone metastases (2/16) and both nodal/bone metastases (1/16). PET-based increase of primary PTV was 116%. PET-based boosts were administered in 19/27 patients (8/19: local, 10/19: nodal, 1/19: both), median boost volume was 31.3 cm3 (range 17.2-80.2) (local) and 19.7 cm3 (range 3.0-109.3) (nodal). PTV was changed in 1/11 (9%) of dRT patients (extension of primary PTV to the lymphatic drainage (RT volume of 644.5 cm3), additional nodal boost (volume of 2.7 cm3, 23.1 Gy)). All patients showed biochemical response (mean PSA decrease 88.8 +/- 14.0%). Nadir PSA was reached 10 months (range 1-17) after end of RT (median 0.07 ng/ml, range 0.002-3.96). Within a median 12 months follow-up (range 3-22/8-24 in sRT/dRT), median PSA was 0.05 ng/ml (range 0.002-8.5) (sRT) and 0.26 ng/ml (range 0.02-2.68) (dRT). CONCLUSIONS: 68Ga-PSMA PET/CT influenced sRT planning in almost 63% and dRT in 9% of patients by change of PTV and additional boosts.

Preclinical Comparison of the 64Cu- and 68Ga-Labeled GRPR-Targeted Compounds RM2 and AMTG, as Well as First-in-Humans [68Ga]Ga-AMTG PET/CT.

Despite the recent success of prostate-specific membrane antigen (PSMA)-targeted compounds for theranostic use in prostate cancer (PCa), alternative options for the detection and treatment of PSMA-negative lesions are needed. We have recently developed a novel gastrin-releasing peptide receptor (GRPR) ligand with improved metabolic stability, which might improve diagnostic and therapeutic efficacy and could be valuable for PSMA-negative PCa patients. Our aim was to examine its suitability for theranostic use. We performed a comparative preclinical study on [64Cu]Cu-/[68Ga]Ga-AMTG ([64Cu]Cu-/[68Ga]Ga-α-Me-l-Trp8-RM2) using [64Cu]Cu-/[68Ga]Ga-RM2 ([64Cu]Cu-/[68Ga]Ga-DOTA-Pip5-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Sta13-Leu14-NH2) as a reference compound and investigated [68Ga]Ga-AMTG in a proof-of-concept study in a PCa patient. Methods: Peptides were labeled with 64Cu (80 °C, 1.0 M NaOAc, pH 5.50) and 68Ga (90 °C, 0.25 M NaOAc, pH 4.50). GRPR affinity (half-maximal inhibitory concentration, room temperature, 2 h) and GRPR-mediated internalization (37 °C, 60 min) were examined on PC-3 cells. Biodistribution studies were performed at 1 h after injection in PC-3 tumor-bearing mice. For a first-in-humans application, 173 MBq of [68Ga]Ga-AMTG were administered intravenously and whole-body PET/CT scans were acquired at 75 min after injection. Results: 64Cu- and 68Ga-labeling proceeded almost quantitatively (>98%). All compounds revealed similarly high GRPR affinity (half-maximal inhibitory concentration, 1.5-4.0 nM) and high receptor-bound fractions (79%-84% of cell-associated activity). In vivo, high activity levels (percentage injected dose per gram) were found in the PC-3 tumor (14.1-15.1 %ID/g) and the pancreas (12.6-30.7 %ID/g), whereas further off-target accumulation was low at 1 h after injection, except for elevated liver uptake observed for both 64Cu-labeled compounds. Overall biodistribution profiles and tumor-to-background ratios were comparable but slightly enhanced for the 68Ga-labeled analogs in most organs. [68Ga]Ga-AMTG confirmed the favorable pharmacokinetics-as evident from preclinical studies-in a patient with metastasized castration-resistant PCa showing intense uptake in several lesions. Conclusion: AMTG is eligible for theranostic use, as labeling with 64Cu and 68Ga, as well as 177Lu (known from previous study), does not have a negative influence on its favorable biodistribution pattern. For this reason, further clinical evaluation is warranted.

Topical 188Re Ionizing Radiation Therapy Exerts High Efficacy in Curing Nonmelanoma Skin Cancer.

PURPOSE OF THE REPORT: Nonmelanoma skin cancer (NMSC) is the most frequent malignancy. Surgical intervention is the common treatment but may lead to disappointing results; alternative treatment options are needed. METHODS: In this monocentric pilot study, topical 188Re resin was investigated as a treatment for invasive NMSC up to 3-mm thickness. Twenty-two patients with 40 histologically confirmed NMSCs with a median size of 1.25 cm2 (range, 0.04-16.8 cm2) and a median tumor thickness of 0.35 mm (range, 0.1-2.1 mm) were included. Patients were treated once with 188Re resin with a targeted dose of 50 Gy. The median applied activity was 111.4 MBq (range, 21.0-168.0 MBq), and the median treatment time was 89 minutes (range, 38-175 minutes). The response rate, adverse events, and cosmetic outcome were assessed at 14 days, 4 months, and 12 months. RESULTS: Response rate at 12 months was 97.5%, with 95% complete responses (clinically or histologically proven in case of clinical doubt). Most adverse events were reported at 14 days, with 20% itching and 12.5% mostly minor pain. Forty-nine percent of the lesions showed hypopigmentation only at 12 months. Forty-one percent of the lesions were graded as cosmetically superior to the expected result after surgery and 51.3% as comparable to successful surgery. The cosmetic outcome on the head and face was superior compared with the trunk and leg (P = 0.003). CONCLUSION: 188Re resin is a highly effective treatment for NMSC up to 3-mm thickness and a valid alternative to surgery, specifically for tumors located on sensitive areas such as nose or ear.

Presurgical 68Ga-PSMA-11 Positron Emission Tomography for Biochemical Recurrence Risk Assessment: A Follow-up Analysis of a Multicenter Prospective Phase 3 Imaging Trial.

BACKGROUND: In the initial staging of patients with high-risk prostate cancer (PCa), prostate-specific membrane antigen positron emission tomography (PSMA-PET) has been established as a front-line imaging modality. The increasing number of PSMA-PET scans performed in the primary staging setting might be associated with decreases in biochemical recurrence (BCR)-free survival (BCR-FS). OBJECTIVE: To assess the added prognostic value of presurgical PSMA-PET for BCR-FS compared with the presurgical Cancer of the Prostate Risk Assessment (CAPRA) and postsurgical CAPRA-Surgery (CAPRA-S) scores in patients with intermediate- to high-risk PCa treated with radical prostatectomy (RP) and pelvic lymph node dissection. DESIGN, SETTING, AND PARTICIPANTS: This is a follow-up study of the surgical cohort evaluated in the multicenter prospective phase 3 imaging trial (n = 277; NCT03368547, NCT02611882, and NCT02919111). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Each 68Ga-PSMA-11-PET scan was read by three blinded independent readers. PSMA-PET prostate uptake (low vs high), PSMA-PET extraprostatic disease (N1/M1), and CAPRA and CAPRA-S scores were used to assess the risk of BCR. Patients were followed after RP by local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level increasing to ≥0.2 ng/ml after RP or initiation of PCa-specific secondary treatment (>6 mo after surgery). Univariate and multivariable Cox models, and c-statistic index were performed to assess the prognostic value of PSMA-PET and for a comparison with the CAPRA and CAPRA-S scores. RESULTS AND LIMITATIONS: From December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median follow-up after surgery was 32.4 (interquartile range 23.3-42.9) mo. Of 240 BCR events, 91 (38%) were observed. PSMA-PET N1/M1 was found in 41/240 (17%) patients. PSMA-PET prostate uptake, PSMA-PET N1/M1, and CAPRA and CAPRA-S scores were significant univariate predictors of BCR. The addition of PSMA-PET N1/M1 status to the presurgical CAPRA score improved the risk assessment for BCR significantly in comparison with the presurgical CAPRA score alone (c-statistic 0.70 [0.64-0.75] vs 0.63 [0.57-0.69]; p < 0.001). The C-index of the postsurgical model utilizing the postsurgical CAPRA-S score alone was not significantly different from the presurgical model combining the presurgical CAPRA score and PSMA-PET N1/M1 status (p = 0.19). CONCLUSIONS: Presurgical PSMA-PET was a strong prognostic biomarker improving BCR-FS risk assessment. Its implementation in the presurgical risk assessment with the CAPRA score improved the performance and reduced the difference with the reference standard (postsurgical CAPRA-S score). PATIENT SUMMARY: The use prostate-specific membrane antigen positron emission tomography improved the assessment of biochemical recurrence risk in patients with intermediate- and high-risk prostate cancer who were treated with radical prostatectomy and pelvic lymph node dissection.

Translational assessment of a DATA-functionalized FAP inhibitor with facile 68Ga-labeling at room temperature.

PURPOSE: The present study aims at evaluating the preclinical and the clinical performance of [68Ga]Ga-DATA5m.SA.FAPi, which has the advantage to be labeled with gallium-68 at room temperature. METHODS: [68Ga]Ga-DATA5m.SA.FAPi was assessed in vitro on FAP-expressing stromal cells, followed by biodistribution and in vivo imaging on prostate and glioblastoma xenografts. Moreover, the clinical assessment of [68Ga]Ga-DATA5m.SA.FAPi was conducted on six patients with prostate cancer, aiming on investigating, biodistribution, biokinetics, and determining tumor uptake. RESULTS: [68Ga]Ga-DATA5m.SA.FAPi is quantitatively prepared in an instant kit-type version at room temperature. It demonstrated high stability in human serum, affinity for FAP in the low nanomolar range, and high internalization rate when associated with CAFs. Biodistribution and PET studies in prostate and glioblastoma xenografts revealed high and specific tumor uptake. Elimination of the radiotracer mainly occurred through the urinary tract. The clinical data are in accordance with the preclinical data concerning the organ receiving the highest absorbed dose (urinary bladder wall, heart wall, spleen, and kidneys). Different to the small-animal data, uptake of [68Ga]Ga-DATA5m.SA.FAPi in tumor lesions is rapid and stable and tumor-to-organ and tumor-to-blood uptake ratios are high. CONCLUSION: The radiochemical, preclinical, and clinical data obtained in this study strongly support further development of [68Ga]Ga-DATA5m.SA.FAPi as a diagnostic tool for FAP imaging.

68Ga-FAPI PET/CT Interobserver Agreement on Tumor Assessment: An International Multicenter Prospective Study.

68Ga-fibroblast activation protein inhibitors (FAPIs) are promising radiotracers for cancer imaging, with emerging data in the recent years. Nonetheless, the interobserver agreement on 68Ga-FAPI PET/CT study interpretations in cancer patients remains poorly understood. Methods: 68Ga-FAPI PET/CT was performed on 50 patients with various tumor entities (sarcoma [n = 10], colorectal cancer [n = 10], pancreatic adenocarcinoma [n = 10], genitourinary cancer [n = 10], and other types of cancer [n = 10]). Fifteen masked observers reviewed and interpreted the images using a standardized approach for local, local nodal, and metastatic involvement. Observers were grouped by experience as having a low (<30 prior 68Ga-FAPI PET/CT studies; n = 5), intermediate (30-300 studies; n = 5), or high level of experience (>300 studies; n = 5). Two independent readers with a high level of experience and unmasked to clinical information, histopathology, tumor markers, and follow-up imaging (CT/MRI or PET/CT) served as the standard of reference (SOR). Observer groups were compared by overall agreement (percentage of patients matching SOR) and Fleiss κ with mean and corresponding 95% CI. We defined acceptable agreement as a κ value of at least 0.6 (substantial or higher) and acceptable accuracy as at least 80%. Results: Highly experienced observers agreed substantially on all categories (primary tumor: κ = 0.71; 95% CI, 0.71-0.71; local nodal involvement: κ = 0.62; 95% CI, 0.61-0.62; distant metastasis: κ = 0.75; 95% CI, 0.75-0.75), whereas observers with intermediate experience showed substantial agreement on primary tumor (κ = 0.73; 95% CI, 0.73-0.73) and distant metastasis (κ = 0.65; 95% CI, 0.65-0.65) but moderate agreement on local nodal stages (κ = 0.55; 95% CI, 0.55-0.55). Observers with low experience had moderate agreement on all categories (primary tumor: κ = 0.57; 95% CI, 0.57-0.58; local nodal involvement: κ = 0.51; 95% CI, 0.51-0.52; distant metastasis: κ = 0.54; 95% CI, 0.53-0.54). Compared with SOR, the accuracy for readers with high, intermediate, and low experience was 85%, 83%, and 78%, respectively. In summary, only highly experienced readers showed substantial agreement and a diagnostic accuracy of at least 80% in all categories. Conclusion: The interpretation of 68Ga-FAPI PET/CT for cancer imaging had substantial reproducibility and accuracy among highly experienced observers only, especially for local nodal and metastatic assessments. Therefore, for accurate interpretation of different tumor entities and pitfalls, we recommend training or experience with at least 300 representative scans for future clinical readers.

GRPr Theranostics: Current Status of Imaging and Therapy using GRPr Targeting Radiopharmaceuticals.

Addressing molecular targets, that are overexpressed by various tumor entities, using radiolabeled molecules for a combined diagnostic and therapeutic (theranostic) approach is of increasing interest in oncology. The gastrin-releasing peptide receptor (GRPr), which is part of the bombesin family, has shown to be overexpressed in a variety of tumors, therefore, serving as a promising target for those theranostic applications. A large amount of differently radiolabeled bombesin derivatives addressing the GRPr have been evaluated in the preclinical as well as clinical setting showing fast blood clearance and urinary excretion with selective GRPr-binding. Most of the available studies on GRPr-targeted imaging and therapy have evaluated the theranostic approach in prostate and breast cancer applying bombesin derivatives tagged with the predominantly used theranostic pair of 68Ga/177Lu which is the focus of this review.

Negative Venous Leg Ultrasound in Acute Pulmonary Embolism: Prevalence, Clinical Characteristics and Predictors.

The purpose of this study was to investigate the prevalence, clinical characteristics, and predictors of negative venous leg ultrasound in acute pulmonary embolism (PE). We retrospectively analyzed a cohort of 168 patients with acute PE (median age 73 years, 44% women) evaluated with complete venous leg ultrasound. A multivariate logistic regression analysis was performed to identify the independent predictors of negative venous ultrasound in acute PE. Venous leg ultrasound was negative for deep venous thrombosis (DVT) in 78 patients (46.4%). Patients with negative venous ultrasound were less likely to have a history of DVT (7.7% vs. 20.0%, p = 0.0273) and had significantly lower D-dimer levels (median 2.5 vs. 6.2 mg/dL p < 0.0001). Negative venous ultrasound was more frequent in PE diagnosed with V/P-SPECT than in PE diagnosed with CT (66.2% vs. 34.0%, p < 0.0001). The prevalence of negative venous ultrasound increased with more peripherally located PE (29.5% for central/lobar, 43.1% for segmental, and 60.6% for subsegmental PE, p = 0.0049). For the multivariate analysis, a diagnosis of PE with V/P-SPECT rather than CT (OR 3.2, p = 0.0056) and lower D-dimer levels (OR 0.94, p = 0.0266) were independent predictors of negative venous ultrasound. In conclusion, venous leg ultrasound was negative for DVT in almost half of patients with acute PE. Negative venous ultrasound was more common in patients with no history of DVT, lower D-dimer levels, PE diagnosed with V/P-SPECT rather than CT, and more peripherally located PE.

Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial.

IMPORTANCE: The presence of pelvic nodal metastases at radical prostatectomy is associated with biochemical recurrence after prostatectomy. OBJECTIVE: To assess the accuracy of prostate-specific membrane antigen (PSMA) 68Ga-PSMA-11 positron emission tomographic (PET) imaging for the detection of pelvic nodal metastases compared with histopathology at time of radical prostatectomy and pelvic lymph node dissection. DESIGN, SETTING, AND PARTICIPANTS: This investigator-initiated prospective multicenter single-arm open-label phase 3 imaging trial of diagnostic efficacy enrolled 764 patients with intermediate- to high-risk prostate cancer considered for prostatectomy at University of California, San Francisco and University of California, Los Angeles from December 2015 to December 2019. Data analysis took place from October 2018 to July 2021. INTERVENTIONS: Imaging scan with 3 to 7 mCi of 68Ga-PSMA-11 PET. MAIN OUTCOMES AND MEASURES: The primary end point was the sensitivity and specificity for the detection pelvic lymph nodes compared with histopathology on a per-patient basis using nodal region correlation. Each scan was read centrally by 3 blinded independent central readers, and a majority rule was used for analysis. RESULTS: A total of 764 men (median [interquartile range] age, 69 [63-73] years) underwent 1 68Ga-PSMA-11 PET imaging scan for primary staging, and 277 of 764 (36%) subsequently underwent prostatectomy with lymph node dissection (efficacy analysis cohort). Based on pathology reports, 75 of 277 patients (27%) had pelvic nodal metastasis. Results of 68Ga-PSMA-11 PET were positive in 40 of 277 (14%), 2 of 277 (1%), and 7 of 277 (3%) of patients for pelvic nodal, extrapelvic nodal, and bone metastatic disease. Sensitivity, specificity, positive predictive value, and negative predictive value for pelvic nodal metastases were 0.40 (95% CI, 0.34-0.46), 0.95 (95% CI, 0.92-0.97), 0.75 (95% CI, 0.70-0.80), and 0.81 (95% CI, 0.76-0.85), respectively. Of the 764 patients, 487 (64%) did not undergo prostatectomy, of which 108 were lost to follow-up. Patients with follow-up instead underwent radiotherapy (262 of 379 [69%]), systemic therapy (82 of 379 [22%]), surveillance (16 of 379 [4%]), or other treatments (19 of 379 [5%]). CONCLUSIONS AND RELEVANCE: This phase 3 diagnostic efficacy trial found that in men with intermediate- to high-risk prostate cancer who underwent radical prostatectomy and lymph node dissection, the sensitivity and specificity of 68Ga-PSMA-11 PET were 0.40 and 0.95, respectively. This academic collaboration is the largest known to date and formed the foundation of a New Drug Application for 68Ga-PSMA-11. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03368547, NCT02611882, and NCT02919111.

Streamlined Schemes for Dosimetry of 177Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer.

(Background) Aim of this retrospective analysis was to investigate in mCRPC patients treated with [177Lu]Lu-PSMA-617 whether the absorbed dose (AD) in organs at risk (OAR, i.e., kidneys and parotid glands) can be calculated using simplified methodologies with sufficient accuracy. For this calculation, results and kinetics of the first therapy cycle were used. (Methods) 46 patients treated with 2 to 6 cycles of [177Lu]Lu-PSMA-617 were included. As reference (current clinical standard) full dosimetry of the OAR based on quantitative imaging (whole body scintigraphy and quantitative SPECT/CT at 2, 24, 48 and 72 h p.i.) for every cycle was used. Alternatively, two dosimetry schemes, simplified in terms of image acquisition and dose calculation, were established, both assuming nearly unchanged kinetics of the radiopharmaceutical for subsequent cycles. (Results) In general, for both OAR the simplified methods provided results that were consistent with the dosimetric reference method, both per cycle and in terms of cumulative AD. Best results were obtained when imaging was performed at 48 h p.i. in each of the subsequent cycles. However, both simplified methods tended to underestimate the cumulative AD. (Conclusion) Simplified dosimetry schemes are feasible to tailor multi-cycle [177Lu]Lu-PSMA-targeted therapies.

Evaluation of [68Ga]Ga-PSMA PET/CT for therapy response assessment of [177Lu]Lu-PSMA radioligand therapy in metastasized castration refractory prostate cancer and correlation with survival.

PURPOSE: The aim of this retrospective study was to evaluate the use of [68Ga]Ga-PSMA PET/CT in therapy response assessment (TRA) of mCRPC patients treated with [177Lu]Lu-PSMA-617 and its correlation with overall survival (OS). METHODS: Thirty-nine patients were included in the study. Patient-/lesion-based early and late response assessment (ERA/LRA) was defined as PET2 (after two therapy cycles) vs. PET1 (before the first cycle) (n = 29) and end of treatment PET vs. PET1 (n = 17), respectively. PET-based response (PET parameters; modified (m) PERCIST/EORTC), biochemical response (ΔPSA; category-based) and category-based clinical response (CRA) was tested for correlation/agreement. PET-based TRA was correlated with OS. RESULTS: A significant correlation/agreement was shown between PET parameters and CRA as well as biochemical response in LRA of all lesions and between mPERCIST-based and category-based PSA response assessment in LRA (bone lesion-based, P = 0.045, κ = 0.184). At ERA, OS was significantly higher in CR/PR/SD compared to progressive disease applying mPERCIST/EORTC criteria (P = 0.0024). CONCLUSION: In [177Lu]Lu-PSMA-617-treated mCRPC patients OS of the group of CR/PR/SD was significantly higher compared to the progressive disease group (mPERCIST/EORTC) in ERA. Therefore, [68Ga]Ga-PSMA PET might serve as a complementary diagnostic tool for TRA offering prognostic value regarding OS.

Imaging of Prostate Cancer.

BACKGROUND: Prostate cancer is the most common type of solid tumor in men and the second most common cause of cancer-related death in males in Germany. The conventional strategy for its primary detection, i.e., systematic ultrasound-guided prostate biopsy in men who have elevated PSA levels and/or positive findings on digital rectal examination, fails to reveal all cases. The same is true of the use of conventional computed tomography (CT), magnetic resonance imaging (MRI), and skeletal scintigraphy for the early detection of recurrences and distant metastases. METHODS: This review is based on pertinent publications retrieved by a selective search, including the German clinical practice guideline on prostate cancer and systematic review articles. RESULTS: Prospective multicenter trials have shown that the detection of clinically significant prostate cancer is markedly improved with multiparametric MRI (mpMRI) and MR/TRUS fusion biopsy (TRUS = transrectal ultrasonography), compared to conventional systematic biopsy. A recent Cochrane review showed that the rate of overdiagnosis of low-risk prostate cancer was reduced with mpMRI and MR/TRUS fusion biopsy compared with conventional systematic biopsy (95/1000 vs. 139/1000), and that clinically significant prostate cancer was more reliably detected (sensitivity 72% vs. 63%), albeit with slightly lower specificity (96% vs. 100%). Prostate- specific membrane antigen (PSMA) hybrid imaging improves the detection of lymphogenic and bony metastases in patients with high-risk prostate cancer. PSMA hybrid imaging is most commonly used to detect biochemical recurrences. A metaanalysis showed that the detection rate depends on the PSA concentration: 74.1% overall, 33.7% with PSA <0.2 ng/mL, and 91.7% with PSA ≥= 2.0 ng/mL. CONCLUSION: The appropriate use of mpMRI and MR/TRUS fusion biopsy improves the initial detection of prostate cancer as well as the assessment of the prognosis. PSMA hybrid imaging is useful for the staging of high-risk patients and for the detection of recurrences. These methods are now recommended in the German clinical practice guideline on prostate cancer as well as in guidelines from other countries.

Anatomical MRI and [18F]FDG PET/CT imaging of Schistosoma mansoni in a NMRI mouse model.

Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether discrimination of infection grade and its correlation to liver damage could be accurately performed by multimodal imaging in a mouse model of Schistosoma mansoni infection. Therefore, groups of uninfected and infected mice underwent MRI and [18F]FDG PET/CT imaging. Anatomical MRI images were used for liver volumetry and for quantification of hepatic granulomas. For PET/CT images a volume of interest based analyses were employed to calculate the [18F]FDG uptake in liver, portal vein, spleen and abdomen. Herein, we demonstrate that the combined use of [18F]FDG-PET/CT and MRI represents an appropriate diagnostic tool for Schistosoma mansoni infection, but fails to discriminate the infection grade and the linked organ damage. Only the splenic [18F]FDG uptake in the 25 cercariae group (5.68 ± 0.90%ID/cc) and 50 cercariae group (4.98 ± 1.43%ID/cc) was significantly higher compared to the control group (2.13 ± 0.69%ID/cc). Nevertheless, future multimodal imaging studies with new radiopharmaceuticals could build a highly sensitive and specific basis for the diagnosis and evaluation of organ damage of schistosomiasis.

Semi-automated Analysis of Ventilation-Perfusion Single-Photon Emission Tomography in the Diagnosis of Pulmonary Embolism - Does it add extra value?

AIM: Diagnosis of pulmonary embolism using V/P-SPECT may include the application of advanced image-processing techniques to identify V/P-mismatches. Aim of this study was to evaluate the benefit in clinical decision making in the diagnosis of pulmonary embolism.by whether adding to conventional reading a software that automatically calculates and visualizes the ventilation/perfusion-quotient pixel by pixel. METHODS: 63 consecutive patients with a clinical suspicion of PE who underwent V/P-SPECT were included in this retrospective study. Images were randomly ordered both for standard as well as for software-assisted reading using V/P-quotients. Studies were read independently by 2 experienced and 2 inexperienced raters. Diagnostic performance and observer agreement of all readers and both reading methods were determined. RESULTS: Expert observers consistently achieved a high diagnostic accuracy both in conventional as well as in software-assisted reporting (sensitivity: 0.94 vs. 0.94, specificity: 0.96 vs. 0.97, LR+: 17.32 vs. 28.86, LR- stayed constant at 0.06). For inexperienced readers, diagnostic performance improved: sensitivity raised from 0.74 to 0.85 and specificity from 0.86 to 0.95, LR+ raised from 5.20 to 15.69, LR- decreased from 0.31 to 0.16. Inter-rater reliability (Fleiss' κ) improved from 0.63 to 0.86 by using V/P quotient. CONCLUSION: Benefit from a software-tool that calculates V/P-ratio automatically is only small when used by experienced physicians If inexperienced readers use the software, the diagnostic accuracy increases. Images generated by automated calculation of V/P-mismatches are easy to read and their use might help to standardize and objectify interpretation of V/P-SPECT in the diagnosis of PE.

FDG PET Hybrid Imaging.

Molecular imaging with positron emission tomography (PET) using tumour-seeking radiopharmaceuticals has gained wide acceptance in oncology with many clinical applications. The hybrid imaging modality PET/CT (computed tomography) allows assessing molecular as well as morphologic information at the same time. Therefore, PET/CT represents an efficient tool for whole-body staging and re-staging within one imaging modality. In oncology, the glucose analogue 18-F-fluorodeoxyglucose (FDG) is the most widely used PET/CT radiopharmaceutical in clinical routine. FDG PET and FDG PET/CT have been used for staging and re-staging of tumour patients in numerous studies. This chapter will discuss the use and the main indications of FDG PET/CT in oncology with special emphasis on lung cancer, lymphoma, head and neck cancer, melanoma and breast cancer (among other tumour entities). A review of the current literature is given with respect to primary diagnosis, staging and diagnosis of recurrent disease. Besides its integral role in diagnosis, staging and re-staging of disease in oncology, there is increasing evidence that FDG PET/CT can be used for therapy response assessment (possibly influencing therapeutic management and treatment planning) by evaluating tumour control, which will also be discussed in this chapter.

Highlights of the 32th Annual Congress of the EANM, Barcelona 2019: the nucleolympic games of nuclear medicine-a global competition for excellence.

The 32th Annual Congress of the European Association of Nuclear Medicine (EANM) returned to Barcelona, Spain, from the 12th to the 16th of October 2019, under the chairmanship of Professor Francesco Giammarile. With a total number of 6833 participants from all over the world, the EANM congress was the year's most important meeting in nuclear medicine worldwide. The congress was an unprecedented success, with more than 1800 submitted abstracts presented in scientific sessions and a variety of lectures including CME sessions from all fields of nuclear medicine and multidisciplinary joint symposia with clinical societies. Innovative research was presented in all fields, showing important developments in radiopharmacy and preclinical oncology, PET and non-PET diagnostic strategies, new therapeutic approaches and molecular imaging-based prediction of prognosis and treatment response. In the field of physics and instrumentation, technological progresses, radiomics and artificial intelligence were highlighted as most relevant areas of innovation. This review gives a summary of our personal choice among the most notable developments of this year's contributions as presented in the Highlights session of the Annual congress of the EANM 2019. EANM 2019 outlines a bright future for nuclear medicine, with groups competing all over the world to bring innovation across all fields of medicine, through increased standardization, progressively lower radiation dose and increasingly high clinical impact.

First-in-human dosimetry of gastrin-releasing peptide receptor antagonist [177Lu]Lu-RM2: a radiopharmaceutical for the treatment of metastatic castration-resistant prostate cancer.

PURPOSE: Besides PSMA, prostate cancer cells also express gastrin-releasing peptide receptor (GRPr) which is therefore a promising target for theranostic approaches. The high affinity GRPr antagonist RM2 can be labeled with beta-emitting radiometals for therapeutic purposes. The aim of this study was to calculate absorbed doses for critical organs and tumor lesions for [177Lu]Lu-RM2 therapy administered in a group of metastatic castration-resistant prostate cancer (mCRPC) patients who had insufficient PSMA expression or showed lower PSMA accumulation after previous cycles of [177Lu]Lu-PSMA-617 therapy. METHODS: Thirty-five patients suffering from mCRPC without further treatment options for approved therapies were examined with [68Ga]Ga-RM2-PET/CT. Out of these, 4 patients (mean age 68 years) were treated with [177Lu]Lu-RM2; two of these also received a 2nd therapy cycle. Mean activity was 4.5 ± 0.9 GBq. For dosimetry, patients underwent planar WB-scintigraphy and SPECT/CT imaging of the upper and lower abdomen at approximately 1, 24, 48, and 72 h p.i. along with blood sampling. Absorbed doses for kidneys, pancreas, liver, spleen, gallbladder wall, and tumor lesions were derived based on quantitative SPECT/CT according to RADAR dosimetry scheme; individual organ masses were extracted from CT. Absorbed dose to bone marrow was calculated based on serial whole-body images and blood sampling according to the EANM guideline. RESULTS: Therapy was well tolerated by all patients and no side effects were observed. An increased uptake in tumor lesions and the pancreas was seen within the first 1 h. Mean absorbed organ doses were 1.08 ± 0.44 Gy/GBq in the pancreas, 0.35 ± 0.14 Gy/GBq in the kidneys, 0.05 ± 0.02 Gy/GBq in the liver, 0.07 ± 0.02 Gy/GBq in the gallbladder wall, 0.10 ± 0.06 Gy/GBq in the spleen, and 0.02 ± 0.01 Gy/GBq for the red bone marrow. The mean dose for tumor lesions was 6.20 ± 3.00 Gy/GBq. CONCLUSIONS: Application of GRPr antagonist [177Lu]Lu-RM2 is suitable for targeted radiotherapy of mCRPC as it shows high tumor uptake and rapid clearance from normal organs. Absorbed doses in tumor lesions are therapeutically relevant. The critical organ receiving the highest absorbed dose was the pancreas. Results suggest that the activity administered for each cycle could be increased to maximize the absorbed dose of tumors and metastases.

[18F]FDG PET/CT for assessing inguinal lymph nodes in patients with penile cancer - correlation with histopathology after inguinal lymphadenectomy.

AIM: Accurate staging of penile cancer requires invasive methods such as sentinel node biopsy or lymphadenectomy (LAD). We assessed the value of [18F]FDG PET/CT for non-invasive nodal staging in penile cancer (PC) patients before inguinal LAD. PATIENTS AND METHODS: 41 consecutive patients with PC (stage pT1 or higher, cN0) received [18F]FDG PET/CT before undergoing bilateral modified or radical inguinal staging LAD. Lymph nodes with a visually increased [18F]FDG uptake were classified as suspicious of lymph node metastases (LNM). Standardized uptake value (SUV) of suspicious inguinal lymph nodes was determined. Results of [18F]FDG PET/CT were correlated with histopathology. RESULTS: In total 623 lymph nodes were resected, in 10 patients LNM were histologically confirmed (14/623 lymph nodes). In patient-based analysis [18F]FDG PET/CT showed a sensitivity and specificity of 80% and 68 %, respectively, a positive predictive value (PPV) of 44 % and a negative predictive value (NPV) of 91 %. In the groin-based analysis, [18F]FDG PET/CT had a sensitivity of 69 %, a specificity of 77 %, a PPV of 36 % and a NPV of 93 %. There was no significant difference in SUVmean and SUVmax between true positive and false positive lymph nodes (p = 0.093 and 0.069, respectively). CONCLUSION: [18F]FDG PET/ CT shows a high NPV in penile cancer patients without clinically evident LNM. However, due to its limited sensitivity (especially with respect to LNM of small size) and specificity (i. e. in the differentiation between (post)inflammatory and metastatic lymph nodes) [18F]FDG PET/CT cannot replace invasive nodal staging.