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Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (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 PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center.
Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly 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 were 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 two individual observers (all four readers selected the same target lesion in 58/125 (46.4%) instances, three readers in 40/125 (32%) and two observers in 27/125 (21.6%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two 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).
Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This 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.
PURPOSE:
We aimed to (a) elucidate the concordance of visual assessment of an initial I-ioflupane scan by a human interpreter with comparison to results using a fully automatic semiquantitative method and (b) to assess the accuracy compared to follow-up (f/u) diagnosis established by movement disorder specialists.
METHODS:
An initial I-ioflupane scan was performed in 382 patients with clinically uncertain Parkinsonian syndrome. An experienced reader performed a visual evaluation of all scans independently. The findings of the visual read were compared with semiquantitative evaluation. In addition, available f/u clinical diagnosis (serving as a reference standard) was compared with results of the human read and the software.
RESULTS:
When comparing the semiquantitative method with the visual assessment, discordance could be found in 25 (6.5%) of 382 of the cases for the experienced reader (ĸ = 0.868). The human observer indicated region of interest misalignment as the main reason for discordance. With neurology f/u serving as reference, the results of the reader revealed a slightly higher accuracy rate (87.7%, ĸ = 0.75) compared to semiquantification (86.2%, ĸ = 0.719, P < 0.001, respectively). No significant difference in the diagnostic performance of the visual read versus software-based assessment was found.
CONCLUSIONS:
In comparison with a fully automatic semiquantitative method in I-ioflupane interpretation, human assessment obtained an almost perfect agreement rate. However, compared to clinical established diagnosis serving as a reference, visual read seemed to be slightly more accurate as a solely software-based quantitative assessment.
Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([\(^{68}\)Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [\(^{68}\)Ga]DOTATATE, we aimed to quantitatively investigate the biodistribution of [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden.
Procedures: Of the 44 included patients, 36/44 (82%) patients demonstrated suspicious radiotracer uptake on [\(^{68}\)Ga]DOTATOC positron emission tomography (PET)/x-ray computed tomography (CT). Volumes of Interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV\(_{mean}\)) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV\(_{mean}\), maximum standardized uptake value (SUV\(_{max}\)), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman’s rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden.
Results: The median SUV\(_{mean}\) was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV\(_{mean}\) 6.9, SUV\(_{max}\) 35.5, TBM 42.6g, and TBU 1.2%. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV\(_{mean}\) increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV\(_{mean}\) nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3%) vs. higher TBU (>7%), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET.
Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [\(^{68}\)Ga]DOTATOC PET/CT. Potential implications include increased normal organ dose with [\(^{177}\)Lu-DOTA]\(^0\)-D-Phe\(^1\)-Tyr\(^3\)-Octreotide and decreased absolute lesion detection with [\(^{68}\)Ga]DOTATOC in high NET burden.
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, e.g. 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 a) increase clinical acceptance of new radiotracers, b) allow for inter- and intra-center comparisons for quality assurance, and c) may be used in (global) multi-center studies to ensure comparable results and enable efficient data abstraction. In the last two years, several standardized framework systems for positron emission tomography (PET) radiotracers with potential theranostic applications have been proposed. These include systems for prostate-specific membrane antigen (PSMA)-targeted PET agents for the diagnosis and treatment of prostate cancer (PCa) and somatostatin receptor (SSTR)-targeted PET agents for the diagnosis and treatment of neuroendocrine neoplasias. In the present review, those standardized framework systems for PSMA- and SSTR-targeted PET 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.
We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
Objective: Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent \(^{18}\)F-DCFPyL.
Methods: A total of 98 patients who underwent \(^{18}\)F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUV\(_{max}\)), and maximum standardized uptake value corrected to lean body mass (SUL\(_{max}\)) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUV\(_{max}\) and SUL\(_{max}\) values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean).
Results: Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated \(^{18}\)F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/ 22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts.
Conclusion: As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients’ cancers must be understood. This is the first systematic evaluation of the uptake of \(^{18}\)F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research.