Lack of repeatability of radiomic features derived from PET scans: Results from a 18 F-DCFPyL test-retest cohort.

OBJECTIVES: PET-based radiomic metrics are increasingly utilized as predictive image biomarkers. However, the repeatability of radiomic features on PET has not been assessed in a test-retest setting. The prostate-specific membrane antigen-targeted compound 18 F-DCFPyL is a high-affinity, high-contrast PET agent that we utilized in a test-retest cohort of men with metastatic prostate cancer (PC). METHODS: Data of 21 patients enrolled in a prospective clinical trial with histologically proven PC underwent two 18 F-DCFPyL PET scans within 7 days, using identical acquisition and reconstruction parameters. Sites of disease were segmented and a set of 29 different radiomic parameters were assessed on both scans. We determined repeatability of quantification by using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. RESULTS: In total, 230 lesions (177 bone, 38 lymph nodes, 15 others) were assessed on both scans. For all investigated radiomic features, a broad range of inter-scan correlation was found (r, 0.07-0.95), with acceptable reproducibility for entropy and homogeneity (wCOV, 16.0% and 12.7%, respectively). On Bland-Altman analysis, no systematic increase or decrease between the scans was observed for either parameter (±1.96 SD: 1.07/-1.30, 0.23/-0.18, respectively). The remaining 27 tested radiomic metrics, however, achieved unacceptable high wCOV (≥21.7%). CONCLUSION: Many common radiomic features derived from a test-retest PET study had poor repeatability. Only Entropy and homogeneity achieved good repeatability, supporting the notion that those image biomarkers may be incorporated in future clinical trials. Those radiomic features based on high frequency aspects of images appear to lack the repeatability on PET to justify further study.

Test-retest repeatability of organ uptake on PSMA-targeted 18 F-DCFPyL PET/CT in patients with prostate cancer.

OBJECTIVES: We evaluated 18 F-DCFPyL test-retest repeatability of uptake in normal organs. METHODS: Twenty-two prostate cancer (PC) patients underwent two 18 F-DCFPyL PET scans within 7 days within a prospective clinical trial (NCT03793543). In both PET scans, uptake in normal organs (kidneys, spleen, liver, and salivary and lacrimal glands) was quantified. Repeatability was determined by using within-subject coefficient of variation (wCOV), with lower values indicating improved repeatability. RESULTS: For SUVmean , repeatability was high for kidneys, spleen, liver, and parotid glands (wCOV, range: 9.0%-14.3%) and lower for lacrimal (23.9%) and submandibular glands (12.4%). For SUVmax , however, the lacrimal (14.4%) and submandibular glands (6.9%) achieved higher repeatability, while for large organs (kidneys, liver, spleen, and parotid glands), repeatability was low (range: 14.1%-45.2%). CONCLUSION: We found acceptable repeatability of uptake on 18 F-DCFPyL PET for normal organs, in particular for SUVmean in the liver or parotid glands. This may have implications for both PSMA-targeted imaging and treatment, as patient selection for radioligand therapy and standardized frameworks for scan interpretation (PROMISE, E-PSMA) rely on uptake in those reference organs.

High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with 18F-DCFPyL.

Objectives: In patients with prostate cancer (PC) receiving prostate-specific membrane antigen- (PSMA-) targeted radioligand therapy (RLT), higher baseline standardized uptake values (SUVs) are linked to improved outcome. Thus, readers deciding on RLT must have certainty on the repeatability of PSMA uptake metrics. As such, we aimed to evaluate the test-retest repeatability of lesion uptake in a large cohort of patients imaged with 18F-DCFPyL. Methods: In this prospective, IRB-approved trial (NCT03793543), 21 patients with history of histologically proven PC underwent two 18F-DCFPyL PET/CTs within 7 days (mean 3.7, range 1 to 7 days). Lesions in the bone, lymph nodes (LN), and other organs were manually segmented on both scans, and uptake parameters were assessed (maximum (SUVmax) and mean (SUVmean) SUVs), PSMA-tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA, defined as PSMA - TV × SUVmean)). Repeatability was determined using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. Results: In total, 230 pairs of lesions (177 bone, 38 LN, and 15 other) were delineated, demonstrating a wide range of SUVmax (1.5-80.5) and SUVmean (1.4-24.8). Including all sites of suspected disease, SUVs had a strong interscan correlation (R 2 ≥ 0.99), with high repeatability for SUVmean and SUVmax (wCOV, 7.3% and 12.1%, respectively). High SUVs showed significantly improved wCOV relative to lower SUVs (P < 0.0001), indicating that high SUVs are more repeatable, relative to the magnitude of the underlying SUV. Repeatability for PSMA-TV and TL-PSMA, however, was low (wCOV ≥ 23.5%). Across all metrics for LN and bone lesions, interscan correlation was again strong (R 2 ≥ 0.98). Moreover, LN-based SUVmean also achieved the best wCOV (3.8%), which was significantly reduced when compared to osseous lesions (7.8%, P < 0.0001). This was also noted for SUVmax (wCOV, LN 8.8% vs. bone 12.0%, P < 0.03). On a compartment-based level, wCOVs for volumetric features were ≥22.8%, demonstrating no significant differences between LN and bone lesions (PSMA-TV, P =0.63; TL-PSMA, P =0.9). Findings on an entire tumor burden level were also corroborated in a hottest lesion analysis investigating the SUVmax of the most intense lesion per patient (R 2, 0.99; wCOV, 11.2%). Conclusion: In this prospective test-retest setting, SUV parameters demonstrated high repeatability, in particular in LNs, while volumetric parameters demonstrated low repeatability. Further, the large number of lesions and wide distribution of SUVs included in this analysis allowed for the demonstration of a dependence of repeatability on SUV, with higher SUVs having more robust repeatability.

Interobserver Agreement Rates on C-X-C Motif Chemokine Receptor 4-Directed Molecular Imaging and Therapy.

BACKGROUND: We aimed to evaluate the interobserver agreement rates in patients scanned with C-X-C motif chemokine receptor 4 (CXCR4)-directed PET/CT, including the rate of patients eligible for CXCR4-targeted radioligand therapy (RLT) based on scan results. METHODS: Four independent observers reviewed 50 CXCR4-targeted [ 68 Ga]pentixafor PET/CT of patients with various solid cancers. On a visual level, the following items were assessed by each reader: overall scan impression, number of organ and lymph node (LN) metastases and number of affected organs and LN regions. For a quantitative investigation, readers had to choose a maximum of 3 target lesions, defined as largest in size and/or most intense uptake per organ compartment. Reference tissues were also quantified, including unaffected hepatic parenchyma and blood pool. Last, all observers had to decide whether patients were eligible for CXCR4-targeted RLT. Concordance rates were tested using intraclass correlation coefficients (ICCs). For interpretation, we applied the definition of Cicchetti (with 0.4-0.59 indicating fair; 0.6-0.74, good; 0.75-1, excellent agreement). RESULTS: On a visual level, fair agreement was achieved for an overall scan impression (ICC, 0.58; 95% confidence interval, 0.45-0.71). Organ and LN involvement (ICC, ≥0.4) demonstrated fair, whereas CXCR4 density and number of LN and organ metastases showed good agreement rates (ICC, ≥0.65). Number of affected organs and affected LN areas, however, showed excellent concordance (ICC, ≥0.76). Quantification in LN and organ lesions also provided excellent agreement rates (ICC, ≥0.92), whereas quantified uptake in reference organs provided fair concordance (ICC, ≥0.54). Again, excellent agreement rates were observed when deciding on patients eligible for CXCR4-RLT (ICC, 0.91; 95% confidence interval, 0.85-0.95). CONCLUSIONS: In patients scanned with CXCR4-targeted PET/CT, we observed fair to excellent agreement rates for both molecular imaging and therapy parameters, thereby favoring a more widespread adoption of [ 68 Ga]pentixafor in the clinic.

High Interobserver Agreement on PSMA PET/CT Even in the Absence of Clinical Data.

BACKGROUND: Recommended by current guidelines, prostate-specific membrane antigen (PSMA)-directed PET/CT is increasingly used in men with prostate cancer (PC). We aimed to provide concordance rates using the PSMA reporting and data system (RADS) for scan interpretation and also determine whether such agreement rates are affected by available patient characteristics at time of scan. PATIENTS AND METHODS: Sixty men with PC, who all underwent 68Ga-PSMA-11 PET/CT, were included. Three independent, experienced readers indicated general scan parameters (including overall scan result, organ or lymph node [LN] involvement, and appropriateness of radioligand therapy). Applying PSMA-RADS 1.0, observers also had to conduct RADS scoring on a target lesion (TL) and overall scan level. During the first read, observers were masked to all relevant clinical information, whereas on a second read, relevant patient characteristics were displayed, thereby allowing for determination of impact of available clinical information for scan interpretation. We used intraclass correlation coefficients (ICCs; with 95% confidence intervals [CIs]), which were then rated according to Cicchetti (0.4-0.59 fair, 0.6-0.74 good, and 0.75-1 excellent agreement). RESULTS: For general parameters, agreement rates were excellent, including an overall scan result (ICC, 0.85; 95% CI, 0.76-0.90), LN metastases (ICC, 0.89; 95% CI, 0.83-0.93), organ involvement (ICC, 0.82; 95% CI, 0.72-0.89), and indication for radioligand therapy (ICC, 0.94; 95% CI, 0.90-0.96). Overall RADS scoring was also excellent with an ICC of 0.91 (95% CI, 0.96-09.4). On a TL-based level, 251 different lesions were selected by the 3 observers (with 73 chosen by all 3 readers). RADS-based concordance rates were fair to excellent: all lesions, ICC of 0.78 (95% CI, 0.67-0.85); LN, ICC of 0.81 (95% CI, 0.63-0.92); skeleton, ICC of 0.55 (95% CI, 0-0.84); and prostate, ICC of 0.48 (95% CI, 0.17-0.78). When performing a second read displaying patient's characteristics, there were only minor modifications to the previously applied RADS scoring on a TL-based level (overall, n = 8): each reader 1 and 2 in 3/60 (5%) instances, and reader 3 in 2/60 (3.3%) instances. The main reason for recategorization (mainly upstaging) was provided information on PSA levels (4/8, 50%). CONCLUSIONS: Applying PSMA-RADS, concordance rates were fair to excellent, whereas relevant modifications were rarely observed after providing clinical data. As such, even in the absence of patient information, standardized frameworks still provide guidance for reading PSMA PETs. Those findings may have implications for a high throughput in a busy PET practice, where patient details cannot always be retrieved at time of scan interpretation or in the context of clinical trials or central reviews in which readers may be blinded to clinical data.

A Novel Radiomics-Based Tumor Volume Segmentation Algorithm for Lung Tumors in FDG-PET/CT after 3D Motion Correction-A Technical Feasibility and Stability Study.

Positron emission tomography (PET) provides important additional information when applied in radiation therapy treatment planning. However, the optimal way to define tumors in PET images is still undetermined. As radiomics features are gaining more and more importance in PET image interpretation as well, we aimed to use textural features for an optimal differentiation between tumoral tissue and surrounding tissue to segment-target lesions based on three textural parameters found to be suitable in previous analysis (Kurtosis, Local Entropy and Long Zone Emphasis). Intended for use in radiation therapy planning, this algorithm was combined with a previously described motion-correction algorithm and validated in phantom data. In addition, feasibility was shown in five patients. The algorithms provided sufficient results for phantom and patient data. The stability of the results was analyzed in 20 consecutive measurements of phantom data. Results for textural feature-based algorithms were slightly worse than those of the threshold-based reference algorithm (mean standard deviation 1.2%-compared to 4.2% to 8.6%) However, the Entropy-based algorithm came the closest to the real volume of the phantom sphere of 6 ccm with a mean measured volume of 26.5 ccm. The threshold-based algorithm found a mean volume of 25.0 ccm. In conclusion, we showed a novel, radiomics-based tumor segmentation algorithm in FDG-PET with promising results in phantom studies concerning recovered lesion volume and reasonable results in stability in consecutive measurements. Segmentation based on Entropy was the most precise in comparison with sphere volume but showed the worst stability in consecutive measurements. Despite these promising results, further studies with larger patient cohorts and histopathological standards need to be performed for further validation of the presented algorithms and their applicability in clinical routines. In addition, their application in other tumor entities needs to be studied.

Interobserver Agreement Rates on Fibroblast Activation Protein Inhibitor-Directed Molecular Imaging and Therapy.

OBJECTIVES: Fibroblast activation protein (FAP) has emerged as a novel target for FAP inhibitor (FAPI)-directed molecular imaging and endoradiotherapy (ERT). We aimed to assess the interobserver agreement rates for interpretation of 68Ga-FAPI-4 PET/CT and decision for ERT. PATIENTS AND METHODS: A random order of 68Ga-FAPI-4 PET/CTs from 49 oncology patients were independently interpreted by 4 blinded readers. Per scan, visual assessment was performed, including overall scan impression, number of organ/lymph node (LN) metastases, and number of affected organs/LN regions. Moreover, a maximum of 3 target lesions, defined as largest in size and/or most intense, per organ compartment were identified, which allowed for an additional quantitative interobserver assessment of LN and organ lesions. To investigate potential reference tissues, quantification also included unaffected liver parenchyma and blood pool. Readers also had to indicate whether FAPI-directed ERT should be considered (based on intensity of uptake and widespread disease). Interobserver agreement rates were evaluated using intraclass correlation coefficients (ICCs) and interpreted according to Cicchetti (with 0.4-0.59 indicating fair, and 0.6-0.74 good, agreement). RESULTS: On a visual basis, the agreement rate for an overall scan impression was fair (ICC, 0.42; 95% confidence interval [CI], 0.27-0.57). The concordance rate for number of affected LN areas was also fair (ICC, 0.59; 95% CI, 0.45-0.72), whereas the number of LN metastases, number of affected organs, and number of organ metastases achieved good agreement rates (ICC, ≥0.63). In a quantitative analysis, concordance rates for LN were good (ICC, 0.70; 0.48-0.88), but only fair for organ lesions (ICC, 0.43; 0.26-0.60). In regards to background tissues, ICCs were good for unaffected liver parenchyma (0.68; 0.54-0.79) and fair for blood pool (0.43; 0.29-0.58). When readers should decide on ERT, concordance rates were also fair (ICC, 0.59; 95% CI, 0.46-0.73). CONCLUSIONS: For FAPI-directed molecular imaging and therapy, a fair to good interobserver agreement rate was achieved, supporting the adoption of this radiotracer for clinical routine and multicenter trials.

Tumor heterogeneity for differentiation between liver tumors and normal liver tissue in 18F-FDG PET/CT.

AIM: Malignancies show higher spatial heterogeneity than normal tissue. We investigated, if textural parameters from FDG PET describing the heterogeneity function as tool to differentiate between tumor and normal liver tissue. METHODS: FDG PET/CT scans of 80 patients with liver metastases and 80 patients with results negative upper abdominal organs were analyzed. Metastases and normal liver tissue were analyzed drawing up to three VOIs with a diameter of 25 mm in healthy liver tissue of the tumoral affected and results negative liver, whilst up to 3 metastases per patient were delineated. Within these VOIs 30 different textural parameters were calculated as well as SUV. The parameters were compared in terms of intra-patient and inter-patient variability (2-sided t test). ROC analysis was performed to analyze predictive power and cut-off values. RESULTS: 28 textural parameters differentiated healthy and pathological tissue (p < 0.05) with high sensitivity and specificity. SUV showed ability to differentiate but with a lower significance. 15 textural parameters as well as SUV showed a significant variation between healthy tissues out of tumour infested and negative livers. Mean intra- and inter-patient variability of metastases were found comparable or lower for 6 of the textural features than the ones of SUV. They also showed good values of mean intra- and inter-patient variability of VOIs drawn in liver tissue of patients with metastases and of results negative ones. CONCLUSION: Heterogeneity parameters assessed in FDG PET are promising to classify tissue and differentiate malignant lesions usable for more personalized treatment planning, therapy response evaluation and precise delineation of tumors for target volume determination as part of radiation therapy planning.

High Interobserver Agreement for the Standardized Reporting System SSTR-RADS 1.0 on Somatostatin Receptor PET/CT.

Recently, a standardized framework system for interpreting somatostatin receptor (SSTR)-targeted PET/CT, termed the SSTR reporting and data system (RADS) 1.0, was introduced, providing reliable standards and criteria for SSTR-targeted imaging. We determined the interobserver reliability of SSTR-RADS for interpretation of 68Ga-DOTATOC PET/CT scans in a multicentric, randomized setting. Methods: A set of 51 randomized 68Ga-DOTATOC PET/CT scans was independently assessed by 4 masked readers with different levels of experience (2 experienced readers and 2 inexperienced readers) trained on the SSTR-RADS 1.0 criteria (based on a 5-point scale from 1 [definitively benign] to 5 [high certainty that neuroendocrine neoplasia is present]). For each scan, SSTR-RADS scores were assigned to a maximum of 5 target lesions (TLs). An overall scan impression based on SSTR-RADS was indicated, and interobserver agreement rates on a TL-based, on an organ-based, and on an overall SSTR-RADS score-based level were computed. The readers were also asked to decide whether peptide receptor radionuclide therapy (PRRT) should be considered on the basis of the assigned RADS scores. Results: Among the selected TLs, 153 were chosen by at least 2 readers (all 4 readers selected the same TLs in 58 of 153 [37.9%] instances). The interobserver agreement for SSTR-RADS scoring among identical TLs was good (intraclass correlation coefficient [ICC] ≥ 0.73 for 4, 3, and 2 identical TLs). For lymph node and liver lesions, excellent interobserver agreement rates were derived (ICC, 0.91 and 0.77, respectively). Moreover, the interobserver agreement for an overall scan impression based on SSTR-RADS was excellent (ICC, 0.88). The SSTR-RADS-based decision to use PRRT also demonstrated excellent agreement, with an ICC of 0.80. No significant differences between experienced and inexperienced readers for an overall scan impression and TL-based SSTR-RADS scoring were observed (P ≥ 0.18), thereby suggesting that SSTR-RADS seems to be readily applicable even for less experienced readers. Conclusion: SSTR-RADS-guided assessment demonstrated a high concordance rate, even among readers with different levels of experience, supporting the adoption of SSTR-RADS for trials, clinical routine, or outcome studies.

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has impacted the management of patients with prostate cancer (PCa) in many parts of the world. PSMA-targeted endoradiotherapies are also being increasingly utilized and for these applications, the radiopharmaceutical distribution in normal organs is particularly important because it may limit the dose that can be delivered to tumors. In this study, we measured both interpatient and intrapatient variability of [18F]DCFPyL uptake in the most relevant normal organs. PROCEDURES: Baseline and 6-month follow-up PSMA-targeted [18F]DCFPyL PET/computed tomography (CT) scans from 39 patients with PCa were reviewed. Volumes of interest were manually drawn using the best visual approximation of the organ edge for both lacrimal glands, all four major salivary glands, the liver, the spleen, and both kidneys for all patients. The average SUVmean, the COVs, and intraclass correlation coefficients (ICCs) across scans were calculated. Bland-Altman analyses were performed for all organs to derive repeatability coefficients (RCs). RESULTS: The liver demonstrated the lowest interpatient variability (13.0 and 16.6 % at baseline and follow-up, respectively), while the spleen demonstrated the largest interpatient variability (44.6 and 51.0 % at baseline and follow-up, respectively). The lowest intrapatient variability was found in the spleen (ICC 0.86) while the highest intrapatient variability was in the kidneys (ICCs 0.40-0.50). Bland-Altman analyses showed 95 % repeatability coefficients for mean uptake > 40 % for multiple organs and were highest for the lacrimal glands, kidneys, and spleen. CONCLUSIONS: Normal organs demonstrate significant variability in uptake of the PSMA-targeted radiotracer [18F]DCFPyL. Depending on the organ, different contributions of interpatient and intrapatient factors affect the intrinsic variability. The RCs also vary significantly among the different organs were highest for the lacrimal glands, kidneys, and spleen. These findings may have important implications for the design of clinical protocols and personalized dosimetry for PSMA-targeted endoradiotherapies.

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Impact of Tumor Burden on Normal Organ Uptake.

PURPOSE: In this study, we aimed to quantitatively investigate the biodistribution of [18F]DCFPyL in patients with prostate cancer (PCa) and to determine whether uptake in normal organs correlates with an increase in tumor burden. PROCEDURES: Fifty patients who had been imaged with [18F]DCFPyL positron emission tomography/computed tomography (PET/CT) were retrospectively included in this study. Forty of 50 (80 %) demonstrated radiotracer uptake on [18F]DCFPyL PET/CT compatible with sites of PCa. Volumes of interests (VOIs) were set on normal organs (lacrimal glands, parotid glands, submandibular glands, liver, spleen, and kidneys) and on tumor lesions. Mean standardized uptake values corrected to lean body mass (SULmean) and mean standardized uptake values corrected to body weight (SUVmean) for normal organs were assessed. For the entire tumor burden, SULmean/max, SUVmean, tumor volume (TV), and the total activity in the VOI were obtained using tumor segmentation. A Spearman's rank correlation coefficient was used to investigate correlations between normal organ uptake and tumor burden. RESULTS: There was no significant correlation between TV with the vast majority of the investigated organs (lacrimal glands, parotid glands, submandibular glands, spleen, and liver). Only the kidney showed significant correlation: With an isocontour threshold at 50 %, left kidney uptake parameters correlated significantly with TV (SUVmean, ρ = - 0.214 and SULmean, ρ = - 0.176, p < 0.05, respectively). CONCLUSIONS: Only a minimal sink effect with high tumor burden in patients imaged with [18F]DCFPyL was observed. Other factors, such as a high intra-patient variability of normal organ uptake, may be a much more important consideration for personalized dosimetry with PSMA-targeted therapeutic agents structurally related to [18F]DCFPyL than the tumor burden.

Novel Structured Reporting Systems for Theranostic Radiotracers.

Standardized reporting is more and more routinely implemented in clinical practice, and such structured reports have a major impact on a large variety of medical fields, such as laboratory medicine, pathology, and, recently, radiology. Notably, the field of nuclear medicine is constantly evolving as novel radiotracers for numerous clinical applications are developed. Thus, framework systems for standardized reporting in this field may increase clinical acceptance of new radiotracers, allow for inter- and intracenter comparisons for quality assurance, and be used in global multicenter studies to ensure comparable results and enable efficient data abstraction. In the last couple of years, several standardized framework systems for PET radiotracers with potential theranostic applications have been proposed. These include systems for prostate-specific membrane antigen-targeted PET agents to diagnose and treat prostate cancer, and systems for somatostatin receptor-targeted PET agents to diagnose and treat neuroendocrine neoplasia. In the present review, the framework systems for these 2 types of cancer will be briefly introduced, followed by an overview of their advantages and limitations. In addition, potential applications will be defined, approaches to validate such concepts will be proposed, and future perspectives will be discussed.

Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on 18F-DCFPyL PET/CT Imaging.

Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted PET imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET examinations in a prospective setting mimicking the typical clinical workflow at a prostate cancer referral center. Methods: Four readers (2 experienced readers (ERs, >3 y of PSMA-targeted PET interpretation experience) and 2 inexperienced readers (IRs, <1 y of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/CT studies independently. Per scan, a maximum of 5 target lesions was selected by the observers, and a PSMA-RADS score for every target lesion was recorded. No specific preexisting conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated, and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed. Results: The number of target lesions identified by each observer was as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least 2 individual observers (all 4 readers selected the same target lesion in 58 of 125 [46.4%] instances, 3 readers in 40 of 125 [32%], and 2 observers in 27 of 125 [21.6%]). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient [ICC] for 4, 3, and 2 identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC, 0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC, 0.84), with a significant difference for ER (ICC, 0.97) vs. IR (ICC, 0.74) (P = 0.005). Conclusion: PSMA-RADS demonstrated a high concordance rate in this study, even among readers with different levels of experience. This finding suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.

Molecular imaging reporting and data systems (MI-RADS): a generalizable framework for targeted radiotracers with theranostic implications.

Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET)-based imaging agents for prostate carcinoma and neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e., if the reader is familiar with one system, the other system can readily be applied, as well. In the present review, we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a potential future role of the umbrella framework MI-RADS compared to other classification systems.