Thyroglobulin measurement is the most powerful outcome predictor in differentiated thyroid cancer: a decision tree analysis in a European multicenter series.

OBJECTIVES: An accurate prognostic assessment is pivotal to adequately inform and individualize follow-up and management of patients with differentiated thyroid cancer (DTC). We aimed to develop a predictive model for recurrent disease in DTC patients treated by surgery and 131I by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, thyroid-stimulating hormone (TSH), thyroglobulin (Tg), administered 131I activities and post-therapy whole body scintigraphy (PT-WBS) were identified as potential predictors and put into regression algorithm (conditional inference tree, c-tree) to develop a risk stratification model for predicting persistent/recurrent disease over time. RESULTS: The PT-WBS pattern identified a partition of the population into two subgroups (PT-WBS positive or negative for distant metastases). Patients with distant metastases exhibited lower disease-free survival (either structural, DFS-SD, and biochemical, DFS-BD, disease) compared to those without metastases. Meanwhile, the latter were further stratified into three risk subgroups based on their Tg values. Notably, Tg values >63.1 ng/mL predicted a shorter survival time, with increased DFS-SD for Tg values <63.1 and <8.9 ng/mL, respectively. A comparable model was generated for biochemical disease (BD), albeit different DFS were predicted by slightly different Tg cutoff values (41.2 and 8.8 ng/mL) compared to DFS-SD. CONCLUSIONS: We developed a simple, accurate and reproducible decision tree model able to provide reliable information on the probability of structurally and/or biochemically persistent/relapsed DTC after a TTA. In turn, the provided information is highly relevant to refine the initial risk stratification, identify patients at higher risk of reduced structural and biochemical DFS, and modulate additional therapies and the relative follow-up.

Radiomics-Based Prediction Model for Outcome of Radioembolization in Metastatic Colorectal Cancer.

PURPOSE: To evaluate the benefit of a contrast-enhanced computed tomography (CT) radiomics-based model for predicting response and survival in patients with colorectal liver metastases treated with transarterial Yttrium-90 radioembolization (TARE). MATERIALS AND METHODS: Fifty-one patients who underwent TARE were included in this single-center retrospective study. Response to treatment was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 3-month follow-up. Patients were stratified as responders (complete/partial response and stable disease, n = 24) or non-responders (progressive disease, n = 27). Radiomic features (RF) were extracted from pre-TARE CT after segmentation of the liver tumor volume. A model was built based on a radiomic signature consisting of reliable RFs that allowed classification of response using multivariate logistic regression. Patients were assigned to high- or low-risk groups for disease progression after TARE according to a cutoff defined in the model. Kaplan-Meier analysis was performed to analyze survival between high- and low-risk groups. RESULTS: Two independent RF [Energy, Maximal Correlation Coefficient (MCC)], reflecting tumor heterogeneity, discriminated well between responders and non-responders. In particular, patients with higher magnitude of voxel values in an image (Energy), and texture complexity (MCC), were more likely to fail TARE. For predicting treatment response, the area under the receiver operating characteristic curve of the radiomics-based model was 0.75 (95% CI 0.48-1). The high-risk group had a shorter overall survival than the low-risk group (3.4 vs. 6.4 months, p < 0.001). CONCLUSION: Our CT radiomics model may predict the response and survival outcome by quantifying tumor heterogeneity in patients treated with TARE for colorectal liver metastases.

Diagnostic Performance of [18F]TFB PET/CT Compared with Therapeutic Activity [131I]Iodine SPECT/CT and [18F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma.

[18F]tetrafluoroborate ([18F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)-based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [18F]TFB PET with high-activity posttherapeutic [131I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [18F]FDG PET/CT in suspected dedifferentiation. Methods: Twenty-six patients treated with high-activity radioactive [131I]iodine therapy (range, 5.00-10.23 GBq) between May 2020 and November 2022 were retrospectively included. Thyroid-stimulating hormone was stimulated by 2 injections of recombinant thyroid-stimulating hormone (0.9 mg) 48 and 24 h before therapy. Before treatment, all patients underwent [18F]TFB PET/CT 40 min after injection of a median of 321 MBq of [18F]TFB. To study tracer kinetics in DTC lesions, 23 patients received an additional scan at 90 min. [131I]iodine therapeutic whole-body scintigraphy and SPECT/CT were performed at a median of 3.8 d after treatment. Twenty-five patients underwent additional [18F]FDG PET. Two experienced nuclear medicine physicians evaluated all imaging modalities in consensus. Results: A total of 62 suspected lesions were identified; of these, 30 lesions were [131I]iodine positive, 32 lesions were [18F]TFB positive, and 52 were [18F]FDG positive. Three of the 30 [131I]iodine-positive lesions were retrospectively rated as false-positive iodide uptake. Tumor-to-background ratio measurements at the 40- and 90-min time points were closely correlated (e.g., for the tumor-to-background ratio for muscle, the Pearson correlation coefficient was 0.91; P < 0.001; n = 49). We found a significant negative correlation between [18F]TFB uptake and [18F]FDG uptake as a potential marker for dedifferentiation (Pearson correlation coefficient, -0.26; P = 0.041; n = 62). Conclusion: Pretherapeutic [18F]TFB PET/CT may help to predict the positivity of recurrent DTC lesions on [131I]iodine scans. Therefore, it may help in the selection of patients for [131I]iodine therapy. Future prospective trials for iodine therapy guidance are warranted. Lesion [18F]TFB uptake seems to be inversely correlated with [18F]FDG uptake and therefore might serve as a dedifferentiation marker in DTC.

Robustness of apparent diffusion coefficient-based lymph node classification for diagnosis of prostate cancer metastasis.

OBJECTIVES: The aim of this proof-of-principle study combining data analysis and computer simulation was to evaluate the robustness of apparent diffusion coefficient (ADC) values for lymph node classification in prostate cancer under conditions comparable to clinical practice. MATERIALS AND METHODS: To assess differences in ADC and inter-rater variability, ADC values of 359 lymph nodes in 101 patients undergoing simultaneous prostate-specific membrane antigen (PSMA)-PET/MRI were retrospectively measured by two blinded readers and compared in a node-by-node analysis with respect to lymph node status. In addition, a phantom and 13 patients with 86 lymph nodes were prospectively measured on two different MRI scanners to analyze inter-scanner agreement. To estimate the diagnostic quality of the ADC in real-world application, a computer simulation was used to emulate the blurring caused by scanner and reader variability. To account for intra-individual correlation, the statistical analyses and simulations were based on linear mixed models. RESULTS: The mean ADC of lymph nodes showing PSMA signals in PET was markedly lower (0.77 × 10-3 mm2/s) compared to inconspicuous nodes (1.46 × 10-3 mm2/s, p < 0.001). High inter-reader agreement was observed for ADC measurements (ICC 0.93, 95%CI [0.92, 0.95]). Good inter-scanner agreement was observed in the phantom study and confirmed in vivo (ICC 0.89, 95%CI [0.84, 0.93]). With a median AUC of 0.95 (95%CI [0.92, 0.97]), the simulation study confirmed the diagnostic potential of ADC for lymph node classification in prostate cancer. CONCLUSION: Our model-based simulation approach implicates a high potential of ADC for lymph node classification in prostate cancer, even when inter-rater and inter-scanner variability are considered. CLINICAL RELEVANCE STATEMENT: The ADC value shows a high diagnostic potential for lymph node classification in prostate cancer. The robustness to scanner and reader variability implicates that this easy to measure and widely available method could be readily integrated into clinical routine. KEY POINTS: • The diagnostic value of the apparent diffusion coefficient (ADC) for lymph node classification in prostate cancer is unclear in the light of inter-rater and inter-scanner variability. • Metastatic and inconspicuous lymph nodes differ significantly in ADC, resulting in a high diagnostic potential that is robust to inter-scanner and inter-rater variability. • ADC has a high potential for lymph node classification in prostate cancer that is maintained under conditions comparable to clinical practice.

Infection Imaging: Focus on New Tracers?

Infections account for relevant morbidity and mortality, especially if the cardiovascular system is affected. Clinical manifestations are often unspecific, resulting in a challenging diagnostic work-up. The use of molecular imaging methods, namely [18F]FDG PET and leukocyte scintigraphy, is increasingly recognized in recently published international guidelines. However, these 2 established methods focus on the host's immune response to the pathogen and are therefore virtually unable to differentiate infection from inflammation. Targeting the microorganism responsible for the infection directly with novel imaging agents is a promising strategy to overcome these limitations. In this review, we discuss clinically approved [18F]FDG PET with its advantages and limitations in cardiovascular infections, followed by new PET-based approaches for the detection of cardiovascular infections by bacteria-specific molecular imaging methods. A multitude of different targeting options has already been preclinically evaluated, but most still lack clinical translation. We give an overview not only on promising tracer candidates for noninvasive molecular imaging of infections but also on issues hampering clinical translation.

177 Lu-DOTATATE (Lutathera) Therapy in 68 Ga-DOTATATE PET/CT-Negative Liver Metastases of a Neuroendocrine Tumor.

ABSTRACT: A 73-year-old man with metastatic pancreatic neuroendocrine tumor was evaluated with 68 Ga-DOTATATE PET/CT for peptide receptor radionuclide therapy. Both PET-positive and negative lesions were seen in the liver, along with extrahepatic metastases. Histopathology was obtained from one of the PET-negative liver lesions to exclude secondary malignancy. Histology confirmed a well-differentiated (G2) metastasis of pNET with high somatostatin receptor expression. We initiated peptide receptor radionuclide therapy with close monitoring of the PET-negative liver metastases. We present a rare case, where posttherapeutic scintigraphy revealed vigorous uptake of 177 Lu-DOTATATE even in the 68 Ga-DOTATATE PET-negative liver metastases. Follow-up PET/CT showed a partial response to therapy.

First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study.

BACKGROUND: Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control. METHODS: Three glioblastoma patients underwent tumor resection followed by standard radio- and chemotherapy. These patients with stable disease following completion of standard therapy underwent iRIT on compassionate grounds. After surgical implantation of a subcutaneous injection reservoir with a catheter into the resection cavity, a leakage test with [99mTc]Tc-DTPA was performed to rule out leakage into other cerebral compartments. IRIT comprised three consecutive applications over three months for each patient, with 25%, 50%, 25% of the total activity injected. A dosimetry protocol was included with blood sampling and SPECT/CT of the abdomen to calculate doses for the bone marrow and kidneys as potential organs at risk. RESULTS: All three patients presented without relevant leakage after application of [99mTc]Tc-DTPA. Two patients underwent three full cycles of iRIT (592 MBq and 1228 MBq total activity). One patient showed histologically proven tumor progression after the second cycle (526 MBq total activity). No relevant therapy-associated toxicities or adverse events were observed. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk. CONCLUSIONS: In first individual cases, iRIT with [177Lu]Lu-6A10-Fab appears to be feasible and safe, without therapy-related side effects. A confirmatory multicenter phase-I-trial was recently opened and is currently recruiting.

Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell-mediated limbic encephalitis.

Autoimmune limbic encephalitis (ALE) presents with new-onset mesial temporal lobe seizures, progressive memory disturbance, and other behavioral and cognitive changes. CD8 T cells are considered to play a key role in those cases where autoantibodies (ABs) target intracellular antigens or no ABs were found. Assessment of such patients presents a clinical challenge, and novel noninvasive imaging biomarkers are urgently needed. Here, we demonstrate that visualization of the translocator protein (TSPO) with [18F]DPA-714-PET-MRI reveals pronounced microglia activation and reactive gliosis in the hippocampus and amygdala of patients suspected with CD8 T cell ALE, which correlates with FLAIR-MRI and EEG alterations. Back-translation into a preclinical mouse model of neuronal antigen-specific CD8 T cell-mediated ALE allowed us to corroborate our preliminary clinical findings. These translational data underline the potential of [18F]DPA-714-PET-MRI as a clinical molecular imaging method for the direct assessment of innate immunity in CD8 T cell-mediated ALE.

Radiomics of Tumor Heterogeneity in 18F-FDG-PET-CT for Predicting Response to Immune Checkpoint Inhibition in Therapy-Naïve Patients with Advanced Non-Small-Cell Lung Cancer.

We aimed to evaluate the predictive and prognostic value of baseline 18F-FDG-PET-CT (PET-CT) radiomic features (RFs) for immune checkpoint-inhibitor (CKI)-based first-line therapy in advanced non-small-cell lung cancer (NSCLC) patients. In this retrospective study 44 patients were included. Patients were treated with either CKI-monotherapy or combined CKI-based immunotherapy-chemotherapy as first-line treatment. Treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). After a median follow-up of 6.4 months patients were stratified into "responder" (n = 33) and "non-responder" (n = 11). RFs were extracted from baseline PET and CT data after segmenting PET-positive tumor volume of all lesions. A Radiomics-based model was developed based on a Radiomics signature consisting of reliable RFs that allow classification of response and overall progression using multivariate logistic regression. These RF were additionally tested for their prognostic value in all patients by applying a model-derived threshold. Two independent PET-based RFs differentiated well between responders and non-responders. For predicting response, the area under the curve (AUC) was 0.69 for "PET-Skewness" and 0.75 predicting overall progression for "PET-Median". In terms of progression-free survival analysis, patients with a lower value of PET-Skewness (threshold < 0.2014; hazard ratio (HR) 0.17, 95% CI 0.06-0.46; p < 0.001) and higher value of PET-Median (threshold > 0.5233; HR 0.23, 95% CI 0.11-0.49; p < 0.001) had a significantly lower probability of disease progression or death. Our Radiomics-based model might be able to predict response in advanced NSCLC patients treated with CKI-based first-line therapy.

Postoperative thyroglobulin as a yard-stick for radioiodine therapy: decision tree analysis in a European multicenter series of 1317 patients with differentiated thyroid cancer.

PURPOSE: An accurate postoperative assessment is pivotal to inform postoperative 131I treatment in patients with differentiated thyroid cancer (DTC). We developed a predictive model for post-treatment whole-body scintigraphy (PT-WBS) results (as a proxy for persistent disease) by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, TSH, and Tg were identified as potential predictors and were put into regression algorithm (conditional inference tree, ctree) to develop a risk stratification model for predicting the presence of metastases in PT-WBS. RESULTS: The lymph node (N) stage identified a partition of the population into two subgroups (N-positive vs N-negative). Among N-positive patients, a Tg value > 23.3 ng/mL conferred a 83% probability to have metastatic disease compared to those with lower Tg values. Additionally, N-negative patients were further substratified in three subgroups with different risk rates according to their Tg values. The model remained stable and reproducible in the iterative process of cross validation. CONCLUSIONS: We developed a simple and robust decision tree model able to provide reliable informations on the probability of persistent/metastatic DTC after surgery. These information may guide post-surgery 131I administration and select patients requiring curative rather than adjuvant 131I therapy schedules.

Correlation of Transcriptomics and FDG-PET SUVmax Indicates Reciprocal Expression of Stemness-Related Transcription Factor and Neuropeptide Signaling Pathways in Glucose Metabolism of Ewing Sarcoma.

BACKGROUND: In Ewing sarcoma (EwS), long-term treatment effects and poor survival rates for relapsed or metastatic cases require individualization of therapy and the discovery of new treatment methods. Tumor glucose metabolic activity varies significantly between patients, and FDG-PET signals have been proposed as prognostic factors. However, the biological basis for the generally elevated but variable glucose metabolism in EwS is not well understood. METHODS: We retrospectively included 19 EwS samples (17 patients). Affymetrix gene expression was correlated with maximal standardized uptake value (SUVmax) using machine learning, linear regression modelling, and gene set enrichment analyses for functional annotation. RESULTS: Expression of five genes correlated (MYBL2, ELOVL2, NETO2) or anticorrelated (FAXDC2, PLSCR4) significantly with SUVmax (adjusted p-value ≤ 0.05). Additionally, we identified 23 genes with large SUVmax effect size, which were significantly enriched for "neuropeptide Y receptor activity (GO:0004983)" (adjusted p-value = 0.0007). The expression of the members of this signaling pathway (NPY, NPY1R, NPY5R) anticorrelated with SUVmax. In contrast, three transcription factors associated with maintaining stemness displayed enrichment of their target genes with higher SUVmax: RNF2, E2F family, and TCF3. CONCLUSION: Our large-scale analysis examined comprehensively the correlations between transcriptomics and tumor glucose utilization. Based on our findings, we hypothesize that stemness may be associated with increased glucose uptake, whereas neuroectodermal differentiation may anticorrelate with glucose uptake.

Fibroblast Activation Protein Triggers Release of Drug Payload from Non-internalizing Small Molecule Drug Conjugates in Solid Tumors.

PURPOSE: Small molecule drug conjugates (SMDC) are modular anticancer prodrugs that include a tumor-targeting small organic ligand, a cleavable linker, and a potent cytotoxic agent. Most of the SMDC products that have been developed for clinical applications target internalizing tumor-associated antigens on the surface of tumor cells. We have recently described a novel non-internalizing small organic ligand (named OncoFAP) of fibroblast activation protein (FAP), a tumor-associated antigen highly expressed in the stroma of most solid human malignancies. EXPERIMENTAL DESIGN: In this article, we describe a new series of OncoFAP-Drug derivatives based on monomethyl auristatin E (MMAE; a potent cytotoxic tubulin poison) and dipeptide linkers that are selectively cleaved by FAP in the tumor microenvironment. RESULTS: The tumor-targeting potential of OncoFAP was confirmed in patients with cancer using nuclear medicine procedures. We used mass spectrometry methodologies to quantify the amount of prodrug delivered to tumors and normal organs, as well as the efficiency of the drug release process. Linkers previously exploited for anticancer drug conjugates were used as benchmark. We identified OncoFAP-Gly-Pro-MMAE as the best performing SMDC, which has now been prioritized for further clinical development. OncoFAP-Gly-Pro-MMAE selectively delivered more than 10% injected dose per gram of MMAE to FAP-positive tumors, with a tumor-to-kidney ratio of 16:1 at 24 hours post-injection. CONCLUSIONS: The FAP-specific drug conjugates described in this article promise to be efficacious for the targeting of human malignancies. The extracellular release of potent anticancer payloads mediates durable complete remission in difficult-to-treat animal models of cancer.

Time after Synthesis and Time after Injection Do Not Affect Diagnostic Quality of [18F]F-PSMA 1007 PET.

PET imaging using PSMA ligands is increasingly used for staging in prostate cancer patients in different clinical indications. Unlike [68Ga]Ga-labeled PSMA ligands, fluorinated compounds can be produced in large amounts; thus, they can be used for a higher number of patients. One concern is that in patients studied a long time after synthesis (TaS) or time after injection (TaI), the specific activity may decline; thus, the signal may be lower in these patients. In this study, we investigated a potential effect of TaS and TaI on image quality. In total, 134 consecutive patients were included in this retrospective analysis on the effect of TaS and TaI on uptake in prostate cancer lesions. All the patients underwent [18F]F-PSMA-1007 PET-CT from 99 min up to 549 min after tracer quality control. TaS and TaI were compared to the quantitative tumoral uptake parameters SUVmax and SUVpeak. In a second exploratory part of the analysis, TaS and TaI were correlated to a physiological tracer uptake in different organs. TaS and TaI did not affect the SUVmax and SUVpeak in tumor lesions in [18F]F-PSMA-1007 PET. The physiological uptake in salivary glands, lacrimal glands and the ganglia, spleen and urine was not significantly correlated to TaS or TaI; in contrast to the mean liver uptake, showing a weak, but significant correlation to TaS. The [18F]F-PSMA-1007 uptake in prostate cancer lesions is not significantly dependent on the TaS and TaI. These results are extremely reassuring when performing [18F]F-PSMA-1007 PET a considerable time after synthesis.

Respiratory motion correction in F-18-FDG PET/CT impacts lymph node assessment in lung cancer patients.

BACKGROUNDS: Elastic motion correction in PET has been shown to increase image quality and quantitative measurements of PET datasets affected by respiratory motion. However, little is known on the impact of respiratory motion correction on clinical image evaluation in oncologic PET. This study evaluated the impact of motion correction on expert readers' lymph node assessment of lung cancer patients. METHODS: Forty-three patients undergoing F-18-FDG PET/CT for the staging of suspected lung cancer were included. Three different PET reconstructions were investigated: non-motion-corrected ("static"), belt gating-based motion-corrected ("BG-MC") and data-driven gating-based motion-corrected ("DDG-MC"). Assessment was conducted independently by two nuclear medicine specialists blinded to the reconstruction method on a six-point scale [Formula: see text] ranging from "certainly negative" (1) to "certainly positive" (6). Differences in [Formula: see text] between reconstruction methods, accounting for variation caused by readers, were assessed by nonparametric regression analysis of longitudinal data. From [Formula: see text], a dichotomous score for N1, N2, and N3 ("negative," "positive") and a subjective certainty score were derived. SUV and metabolic tumor volumes (MTV) were compared between reconstruction methods. RESULTS: BG-MC resulted in higher scores for N1 compared to static (p = 0.001), whereas DDG-MC resulted in higher scores for N2 compared to static (p = 0.016). Motion correction resulted in the migration of N1 from tumor free to metastatic on the dichotomized score, consensually for both readers, in 3/43 cases and in 2 cases for N2. SUV was significantly higher for motion-corrected PET, while MTV was significantly lower (all p < 0.003). No significant differences in the certainty scores were noted. CONCLUSIONS: PET motion correction resulted in significantly higher lymph node assessment scores of expert readers. Significant effects on quantitative PET parameters were seen; however, subjective reader certainty was not improved.

Simultaneous FAPI PET/MRI Targeting the Fibroblast-Activation Protein for Breast Cancer.

Background Integrated PET/MRI is a promising modality for breast assessment. The most frequently used tracer, fluorine 18 (18F) fluorodeoxyglucose (FDG), is applied for whole-body staging in advanced breast cancer but has limited accuracy in evaluating primary breast lesions. The fibroblast-activation protein (FAP) is abundantly expressed in invasive breast cancer. FAP-directed PET tracers have recently become available, but results in primary breast tumors remain lacking. Purpose To evaluate the use of FAP inhibitor (FAPI) breast PET/MRI in assessing breast lesions and of FAPI whole-body scanning for lymph node (LN) and distant staging using the ligand gallium 68 (68Ga)-FAPI-46. Materials and Methods In women with histologically confirmed invasive breast cancer, all primary 68Ga-FAPI-46 breast and whole-body PET/MRI and PET/CT examinations conducted at the authors' center between October 2019 and December 2020 were retrospectively analyzed. MRI lesion characteristics and standardized uptake values (SUVs) were quantified with dedicated software. Mann-Whitney U tests were used to compare tumor SUVs across different tumor types. The Pearson correlation coefficient was calculated between SUV and measures of MRI morphologic characteristics. Results Nineteen women (mean age, 49 years ± 9 [standard deviation]) were evaluated-18 to complement initial staging and one for restaging after therapy for distant metastases. Strong tracer accumulation was observed in all 18 untreated primary breast malignancies (mean maximum SUV [SUVmax] = 13.9 [range, 7.9-29.9]; median lesion diameter = 26 mm [range, 9-155 mm]), resulting in clear tumor delineation across different gradings, receptors, and histologic types. All preoperatively verified LN metastases in 13 women showed strong tracer accumulation (mean SUVmax= 12.2 [range, 3.3-22.4]; mean diameter = 21 mm [range, 14-35 mm]). Tracer uptake established or supported extra-axillary LN involvement in seven women and affected therapy decisions in three women. Conclusion This retrospective analysis indicates use of 68Ga fibroblast-activation protein inhibitor tracers for breast cancer diagnosis and staging. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mankoff and Sellmyer in this issue.

18F-FDG-PET-MRI for the assessment of acute intestinal graft-versus-host-disease (GvHD).

BACKGROUND: Graft versus host disease (GvHD) is a frequent complication of allogeneic stem cell transplantation (alloSCT), significantly increasing mortality. Previous imaging studies focused on the assessment of intestinal GvHD with contrast-enhanced MRI/CT or 18F-FDG-PET imaging alone. The objective of this retrospective study was to elucidate the diagnostic value of a combined 18F-FDG-PET-MRI protocol in patients with acute intestinal GvHD. METHODS: Between 2/2015 and 8/2019, 21 patients with acute intestinal GvHD underwent 18F-FDG-PET-MRI. PET, MRI and PET-MRI datasets were independently reviewed. Readers assessed the number of affected segments of the lower gastrointestinal tract and the reliability of the diagnosis on a 5-point Likert scale and quantitative PET (SUVmax, SUVpeak, metabolic volume (MV)) and MRI parameter (wall thickness), were correlated to clinical staging of acute intestinal GvHD. RESULTS: The detection rate for acute intestinal GvHD was 56.8% for PET, 61.4% for MRI and 100% for PET-MRI. PET-MRI (median Likert-scale value: 5; range: 4-5) offers a significantly higher reliability of the diagnosis compared to PET (median: 4; range: 2-5; p = 0.01) and MRI alone (median: 4; range: 3-5; p = 0.03). The number of affected segments in PET-MRI (rs = 0.677; p <  0.001) and the MV (rs = 0.703; p <  0.001) correlated significantly with the clinical stage. SUVmax (rs = 0.345; p = 0.14), SUVpeak (rs = 0.276; p = 0.24) and wall thickening (rs = 0.174; p = 0.17) did not show a significant correlation to clinical stage. CONCLUSION: 18F-FDG-PET-MRI allows for highly reliable assessment of acute intestinal GvHD and adds information indicating clinical severity.

Lutetium-177 Labelled PSMA Targeted Therapy in Advanced Prostate Cancer: Current Status and Future Perspectives.

Patients suffering from metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis. As a further treatment option 177Lutetium (Lu) prostate-specific membrane antigen (PSMA) radioligand therapy gained a significant interest of many investigators. Several publications showed great response and prolonged survival with limited adverse events. However, to this point, it still remains unclear which patients benefit the most from 177Lu-PSMA therapy, and how to improve the treatment regimen to achieve best outcome while minimizing potential adverse events. The efficacy for mCRPC patients is a given fact, and with the newly published results of the VISION trial its approval is only a matter of time. Recently, investigators started to focus on treating prostate cancer patients in earlier disease stages and in combination with other compounds. This review gives a brief overview of the current state and the future perspectives of 177Lu labelled PSMA radioligand therapy.

Evaluation of 68Ga-PSMA-11 PET-MRI in Patients with Advanced Prostate Cancer Receiving 177Lu-PSMA-617 Therapy: A Radiomics Analysis.

177Lutetium PSMA-617 (Lu-PSMA) therapy in patients with metastatic castration resistant prostate cancer (mCRPC) has gained visibility through the ongoing phase III trial. The data on prediction of therapy outcome and survival out of pretherapeutic imaging parameters is still sparse. In this study, the predictive and prognostic value of radiomic features from 68Ga-PSMA-11 PET-MRI are analyzed. In total, 21 patients with mCRPC underwent 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy. The PET-positive tumor volume was defined and transferred to whole-body T2-, T1- and contrast-enhanced T1-weighted MRI-sequences. The radiomic features from PET and MRI sequences were extracted by using a freely available software package. For selecting features that allow differentiation of biochemical response (PSA decrease > 50%), a stepwise dimension reduction was performed. Logistic regression models were fitted, and selected features were tested for their prognostic value (overall survival) in all patients. Eight patients achieved biochemical response after Lu-PSMA therapy. Ten independent radiomic features differentiated well between responders and non-responders. The logistic regression model, including the feature interquartile range from T2-weighted images, revealed the highest accuracy (AUC = 0.83) for the prediction of biochemical response after Lu-PSMA therapy. Within the final model, patients with a biochemical response (p = 0.003) and higher T2 interquartile range values in pre-therapeutic imaging (p = 0.038) survived significantly longer. This proof-of-concept study provides first evidence on a potential predictive and prognostic value of radiomic analysis of pretherapeutic 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy.