Fully-automated production of [68Ga]Ga-PentixaFor on the module Modular Lab-PharmTracer

BACKGROUND: PentixaFor is a promising radiopharmaceutical for positron emission tomography in the detection of different tumor entities and other diseases. Until now, the synthesis of [68Ga]Ga-PentixaFor was reported for the automated synthesis module from Scintomics® only. Our aim was to evaluate the automated synthesis of this radiopharmaceutical on a different module in order to make it available for a broader community. RESULTS: The synthesis of [68Ga]Ga-PentixaFor with different amounts of PentixaFor (50 μg, 30 μg and 20 μg) on the Modular Lab PharmTracer (MLPT) from Eckert & Ziegler with the already established synthesis template for [68Ga]Ga-DOTATOC yielded best results with 50 μg PentixaFor for clinical multi-dose application. All different quality control parameters tested (e.g. sterility, stability and radiochemical purity) were in accordance with the European Pharmacopoeia. CONCLUSIONS: [68Ga]Ga-PentixaFor was successfully synthesized fully-automated on the synthesis module Modular Lab PharmTracer and can be used for multi-dose application in clinical settings

Prostate Cancer Nodal Staging: Using Deep Learning to Predict 68Ga-PSMA-Positivity from CT Imaging Alone

Lymphatic spread determines treatment decisions in prostate cancer (PCa) patients. 68Ga-PSMA-PET/CT can be performed, although cost remains high and availability is limited. Therefore, computed tomography (CT) continues to be the most used modality for PCa staging. We assessed if convolutional neural networks (CNNs) can be trained to determine 68Ga-PSMA-PET/CT-lymph node status from CT alone. In 549 patients with 68Ga-PSMA PET/CT imaging, 2616 lymph nodes were segmented. Using PET as a reference standard, three CNNs were trained. Training sets balanced for infiltration status, lymph node location and additionally, masked images, were used for training. CNNs were evaluated using a separate test set and performance was compared to radiologists' assessments and random forest classifiers. Heatmaps maps were used to identify the performance determining image regions. The CNNs performed with an Area-Under-the-Curve of 0.95 (status balanced) and 0.86 (location balanced, masked), compared to an AUC of 0.81 of experienced radiologists. Interestingly, CNNs used anatomical surroundings to increase their performance, "learning" the infiltration probabilities of anatomical locations. In conclusion, CNNs have the potential to build a well performing CT-based biomarker for lymph node metastases in PCa, with different types of class balancing strongly affecting CNN performance

Quantitative biparametric analysis of hybrid 18F-FET PET/MR-neuroimaging for differentiation between treatment response and recurrent glioma

We investigated the diagnostic potential of simultaneous 18F-FET PET/MR-imaging for differentiation between recurrent glioma and post-treatment related effects (PTRE) using quantitative volumetric (3D-VOI) lesion analysis. In this retrospective study, a total of 42 patients including 32 patients with histologically proven glioma relapse and 10 patients with PTRE (histopathologic follow-up, n = 4, serial imaging follow-up, n = 6) were evaluated regarding recurrence. PET/MR-imaging was semi-automatically analysed based on FET tracer uptake using conservative SUV thresholding (isocontour 80%) with emphasis on the metabolically most active regions. Mean (relative) apparent diffusion coefficient (ADCmean, rADCmean), standardised-uptake-value (SUV) including target-to-background (TBR) ratio were determined. Glioma relapse presented higher ADCmean (MD ± SE, 284 ± 91, p = 0.003) and TBRmax (MD ± SE, 1.10 ± 0.45, p = 0.02) values than treatment-related changes. Both ADCmean (AUC ± SE = 0.82 ± 0.07, p-value < 0.001) and TBRmax (AUC ± SE = 0.81 ± 0.08, p-value < 0.001) achieved reliable diagnostic performance in differentiating glioma recurrence from PTRE. Bivariate analysis based on a combination of ADCmean and TBRmax demonstrated highest diagnostic accuracy (AUC ± SE = 0.90 ± 0.05, p-value < 0.001), improving clinical (false negative and false positive) classification. In conclusion, biparametric analysis using DWI and FET PET, both providing distinct information regarding the underlying pathophysiology, presented best diagnostic accuracy and clinical benefit in differentiating recurrent glioma from treatment-related changes

Radionuclide, magnetic resonance and computed tomography imaging in European round back slugs (Arionidae) and leopard slugs (Limacidae)

Other than in animal models of human disease, little functional imaging has been performed in most of the animal world. The aim of this study was to explore the functional anatomy of the European round back slug (Arionidae) and leopard slug (Limacidae) and to establish an imaging protocol for comparative species study. Radionuclide images with single photon emission computed tomography (SPECT) and positron emission tomography (PET) were obtained after injections of standard clinical radiopharmaceuticals (99m)technetium dicarboxypropane diphosphonate (bone scintigraphy), (99m)technetium mercaptoacetyltriglycine (kidney function), (99m)technetium diethylenetriaminepentaacetic acid (kidney function), (99m)technetium pertechnetate (mediated by the sodium-iodide symporter), (99m)technetium sestamibi (cardiac scintigraphy) or F-18-fluoro-deoxyglucose (glucose metabolism) in combination with magnetic resonance imaging (MRI) and computed tomography (CT) for uptake anatomic definition. Images were compared with anatomic drawings for the Arionidae species. Additionally, organ uptake data was determined for a description of slug functional anatomy in comparison to human tracer biodistribution patterns identifying the heart, the open circulatory anatomy, calcified shell remnant, renal structure (nephridium), liver (digestive gland) and intestine. The results show the detailed functional anatomy of Arionidae and Limacidae, and describe an in vivo whole-body imaging procedure for invertebrate species

Author Correction: Quantitative biparametric analysis of hybrid 18F-FET PET/MR-neuroimaging for differentiation between treatment response and recurrent glioma

An amendment to this paper has been published and can be accessed via a link at the top of the paper

68Ga-PSMA-PET/CT for the evaluation of liver metastases in patients with prostate cancer

BACKGROUND: The purpose of this study was to evaluate the imaging properties of hepatic metastases in 68Ga-PSMA positron emission tomography (PET) in patients with prostate cancer (PC). METHODS: 68Ga-PSMA-PET/CT scans of PC patients available in our database were evaluated retrospectively for liver metastases. Metastases were identified using 68Ga-PSMA-PET, CT, MRI and follow-up scans. Different parameters including, maximum standardized uptake values (SUVmax) of the healthy liver and liver metastases were assessed by two- and three-dimensional regions of interest (2D/3D ROI). RESULTS: One hundred three liver metastases in 18 of 739 PC patients were identified. In total, 80 PSMA-positive (77.7%) and 23 PSMA-negative (22.3%) metastases were identified. The mean SUVmax of PSMA-positive liver metastases was significantly higher than that of the normal liver tissue in both 2D and 3D ROI (p ≤ 0.05). The mean SUVmax of PSMA-positive metastases was 9.84 ± 4.94 in 2D ROI and 10.27 ± 5.28 in 3D ROI; the mean SUVmax of PSMA-negative metastases was 3.25 ± 1.81 in 2D ROI and 3.40 ± 1.78 in 3D ROI, and significantly lower than that of the normal liver tissue (p ≤ 0.05). A significant (p ≤ 0.05) correlation between SUVmax in PSMA-positive liver metastases and both size (ρSpearman = 0.57) of metastases and PSA serum level (ρSpearman = 0.60) was found. CONCLUSIONS: In 68Ga-PSMA-PET, the majority of liver metastases highly overexpress PSMA and is therefore directly detectable. For the analysis of PET images, it has to be taken into account that also a significant portion of metastases can only be detected indirectly, as these metastases are PSMA-negative

Accuracy of standard clinical 3T prostate MRI for pelvic lymph node staging: Comparison to 68Ga-PSMA PET-CT

The aim was to assess the performance of prostate 3T MRI for pelvic lymph node (LN) staging in prostate cancer (PCa), in comparison to 68Gallium-prostate specific membrane antigen PET-CT (68Ga-PSMA PET-CT) as reference standard for LN detection. 130 patients with PCa underwent non-contrast-enhanced multiparametric prostate 3T MRI and 68Ga-PSMA-PET-CT within 180 days at our institution. Overall, 187 LN metastases (n = 43 patients) detected by 68Ga-PSMA-PET-CT were characterized by calculating maximum standardized uptake value (SUVmax), area, diameter and anatomical location including iliac, obturator, presacral and inguinal region. MRI achieved an overall sensitivity, specificity, positive and negative predictive value of 81.6% (CI 71.1-88.9%), 98.6% (CI 97.6-99.2%), 73.5% (CI 52.1-87.6%) and 99.5% (CI 98.8-99.8%), respectively. On a region-based analysis, detection rates differed non-significantly (ps > 0.12) in the anatomical regions. On a size-dependent analysis, detection of LN > 10 mm did not differ significantly (ps > 0.09) from LN ≤ 10 mm. In comparison to single T1 sequence evaluation, additional use of the T2 weighted sequences did not improve the overall performance significantly (p > 0.05). 3T prostate MRI represented an accurate tool for the detection of LN compared to 68Ga-PSMA-PET-CT. Especially for LN metastases smaller than 10 mm, MRI was less accurate compared to 68Ga-PSMA-PET-CT

Correlation between Intraprostatic PSMA Uptake and MRI PI-RADS of [68Ga]Ga-PSMA-11 PET/MRI in Patients with Prostate Cancer: Comparison of PI-RADS Version 2.0 and PI-RADS Version 2.1

Purpose: We aimed to evaluate the correlation between PSMA uptake and magnetic resonance imaging (MRI) PI-RADS of simultaneous [68Ga]Ga-PSMA-11 PET/MRI regarding PI-RADS version 2.0 and 2.1 respectively and compared the difference between these two versions. Materials and methods: We retrospectively analyzed a total of forty-six patients with biopsy-proven prostate cancer who underwent simultaneous [68Ga]Ga-PSMA-11 PET/MRI. We classified the lesions regarding PI-RADS version 2.0 and 2.1, peripheral zone (PZ), and transitional zone (TZ), respectively. Based on regions of interest (ROI), standardized uptake values maximum (SUVmax), and corresponding lesion-to-background ratios (LBR) of SUVmax of each category, PI-RADS score 1 to 5, were measured. A comparison between PI-RADS version 2.0 and PI-RADS version 2.1 was performed. Results: A total of 215 focal prostate lesions were analyzed, including two subgroups, 125 TZ and 90 PZ. Data are reported as median and interquartile range (IQR). Regarding PI-RADS version 2.1, TZ SUVmax of each category were 1.5 (0.5, 1.9), 1.9 (0.8, 2.3), 3.3 (2.1, 4.6), 4.2 (3.1, 5.7), 7.3 (5.2, 9.7). PZ SUVmax of each category were 1.0 (0.8, 1.6), 2.5 (1.5, 3.2), 3.3 (1.9, 4.5), 4.3 (3.0, 5.4), 7.4 (5.0, 9.3). Regarding the inter-reader agreement of the overall PI-RADS assessment category, the kappa value was 0.723 for version 2.0 and 0.853 for version 2.1. Conclusion: Revisions of PI-RADS version 2.1 results in variations in lesions classification. Lesions with the PI-RADS category of 3, 4, and 5 present relatively higher intraprostatic PSMA uptake, while lesions with the PI-RADS category of 1 and 2 present relatively lower and similar uptake. Version 2.1 has higher inter-reader reproducibility than version 2.0

Somatostatin receptor PET/CT in restaging of typical and atypical lung carcinoids

Background To assess the role of somatostatin receptor (SR) PET/CT using Ga-68 DOTATOC or DOTATATE in staging and restaging of typical (TC) and atypical (AC) lung carcinoids. Methods Clinical and PET/CT data were retrospectively analyzed in 27 patients referred for staging (N = 5; TC, N = 4; AC, N = 1) or restaging (N = 22; TC, N = 8; AC, N = 14). Maximum standardized uptake value (SUVmax) of SR-positive lesions was normalized to the SUVmax of the liver to generate SUVratio; SR PET was compared to contrast-enhanced (ce) CT. The classification system proposed by Rindi et al. (Endocr Relat Cancer. 2014;21(1):1-16, 2014) was used for classification of patients in TC and AC groups. Results Only 18/27 patients were found to have metastases on PET/CT. Of the 186 lesions, 101 (54.3 %) were depicted on both PET and CT, 53 (28.5 %) lesions only on CT, and 32 (17.2 %) only on PET. SUVratio of lesions was significantly higher in AC as compared to TC (p < 0.001). In patients referred for restaging, additional findings on PET lead to upstaging with change in management strategy in 5/22 (22.7 %) patients (AC, N = 5; TC, N = 1). In four patients (all AC) referred for restaging and in one patient (TC) referred for staging, additional findings on CT missed on PET lead to correct staging. Conclusions Typical and atypical carcinoid patients have complex patterns of metastases which make it necessary to combine functional SR PET and contrast- enhanced CT for appropriate restaging. In patients referred for restaging SR, PET may have a relevant impact on treatment strategy in up to 22.7 of patients with typical and atypical lung carcinoids

Increasing molar activity by HPLC purification improves 68Ga-DOTA-NAPamide tumor accumulation in a B16/F1 melanoma xenograft model

Purpose: Melanocortin receptor 1 (MC1R) is overexpressed in melanoma and may be a molecular target for imaging and peptide receptor radionuclide therapy. 68Gallium (68Ga) labeling of DOTA-conjugated peptides is an established procedure in the clinic for use in positron emission tomography (PET) imaging. Aim of this study was to compare a standard labeling protocol against the 68Ga-DOTA peptide purified from the excess of unlabeled peptide. Procedures: The MC1R ligand DOTA-NAPamide was labeled with 68Ga using a standard clinical protocol. Radioactive peptide was separated from the excess of unlabeled DOTA-NAPamide by HPLC. Immediately after the incubation of peptide and 68Ga (95˚C, 15 min), the reaction was loaded on a C18 column and separated by a water/acetonitrile gradient, allowing fractionation in less than 20 minutes. Radiolabeled products were compared in biodistribution studies and PET imaging using nude mice bearing MC1R-expressing B16/F1 xenograft tumors. Results: In biodistribution studies, non-purified 68Ga-DOTA-NAPamide did not show significant uptake in the tumor at 1 h post injection (0.78% IA/g). By the additional HPLC step, the molar activity was raised around 10,000-fold by completely removing unlabeled peptide. Application of this rapid purification strategy led to a more than 8-fold increase in tumor uptake (7.0% IA/g). The addition of various amounts of unlabeled DOTA-NAPamide to the purified product led to a blocking effect and decreased specific tumor uptake, similar to the result seen with non-purified radiopeptide. PET imaging was performed using the same tracer preparations. Purified 68Ga-DOTA-NAPamide, in comparison, showed superior tumor uptake. Conclusions: We demonstrated that chromatographic separation of radiolabeled from excess unlabeled peptide is technically feasible and beneficial, even for short-lived isotopes such as 68Ga. Unlabeled peptide molecules compete with receptor binding sites in the target tissue. Purification of the radiopeptide therefore improved tumor uptake