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  • 1
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    Whole-Body [18F]FDG PET/CT Can Alter Diagnosis in Patients with Suspected Rheumatic Disease
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 11 ( 2021-11-09), p. 2073-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 11 ( 2021-11-09), p. 2073-
    Abstract: The 2-deoxy-d-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is widely utilized to assess the vascular and articular inflammatory burden of patients with a suspected diagnosis of rheumatic disease. We aimed to elucidate the impact of [18F] FDG PET/CT on change in initially suspected diagnosis in patients at the time of the scan. Thirty-four patients, who had undergone [18F]FDG PET/CT, were enrolled and the initially suspected diagnosis prior to [18F] FDG PET/CT was compared to the final diagnosis. In addition, a semi-quantitative analysis including vessel wall-to-liver (VLR) and joint-to-liver (JLR) ratios was also conducted. Prior to [18F]FDG PET/CT, 22/34 (64.7%) of patients did not have an established diagnosis, whereas in 7/34 (20.6%), polymyalgia rheumatica (PMR) was suspected, and in 5/34 (14.7%), giant cell arteritis (GCA) was suspected by the referring rheumatologists. After [18F] FDG PET/CT, the diagnosis was GCA in 19/34 (55.9%), combined GCA and PMR (GCA + PMR) in 9/34 (26.5%) and PMR in the remaining 6/34 (17.6%). As such, [18F]FDG PET/CT altered suspected diagnosis in 28/34 (82.4%), including in all unclear cases. VLR of patients whose final diagnosis was GCA tended to be significantly higher when compared to VLR in PMR (GCA, 1.01 ± 0.08 (95%CI, 0.95–1.1) vs. PMR, 0.92 ± 0.1 (95%CI, 0.85–0.99), p = 0.07), but not when compared to PMR + GCA (1.04 ± 0.14 (95%CI, 0.95–1.13), p = 1). JLR of individuals finally diagnosed with PMR (0.94 ± 0.16, (95%CI, 0.83–1.06)), however, was significantly increased relative to JLR in GCA (0.58 ± 0.04 (95%CI, 0.55–0.61)) and GCA + PMR (0.64 ± 0.09 (95%CI, 0.57–0.71); p 〈 0.0001, respectively). In individuals with a suspected diagnosis of rheumatic disease, an inflammatory-directed [18F]FDG PET/CT can alter diagnosis in the majority of the cases, particularly in subjects who were referred because of diagnostic uncertainty. Semi-quantitative assessment may be helpful in establishing a final diagnosis of PMR, supporting the notion that a quantitative whole-body read-out may be useful in unclear cases.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11112073
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 2
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    Changing Threshold-Based Segmentation Has No Relevant Impact on Semi-Quantification in the Context of Structured Reporting for PSMA-PET/CT
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 2 ( 2022-01-06), p. 270-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 2 ( 2022-01-06), p. 270-
    Abstract: Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with 18F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUVmax, SUVpeak, SUVmean) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50%). SUVmax was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUVmax and SUVpeak compared to the entire PSMA-RADS-4 or -5 cohort (p 〈 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p 〈 0.0001), but not to the PSMA-RADS-4 cohort (SUVmax, p = 0.07; SUVpeak, p = 0.08). SUVmean (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUVmax was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in 18F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUVmean and TL-PSMA in contrast to PSMA-TV.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14020270
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 3
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    Theranostics in Oncology—Thriving, Now More than Ever
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 5 ( 2021-04-29), p. 805-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 5 ( 2021-04-29), p. 805-
    Abstract: Tracing its roots back to the 1940s, theranostics in nuclear oncology has proved successful mainly due to the beneficial effects of image-guided therapeutic concepts for patients afflicted with a variety of different cancers. The majority of these treatments are not only characterized by substantial prolongation of progression-free and overall survival, but are also generally safe, rendering theranostic agents as an attractive treatment option in various clinical scenarios in oncology. In this Special Issue Novel Theranostic Agents, nine original articles from around the globe provide further evidence on the use of the theranostic concept for neuroendocrine neoplasm (NEN), prostate cancer (PC), meningioma, and neuroblastoma. The investigated diagnostic and therapeutic radiotracers target not only established structures, such as somatostatin receptor, prostate-specific membrane antigen or norepinephrine transporter, but also recently emerging targets such as the C-X-C motif chemokine receptor 4. Moreover, the presented original articles also combine the concept of theranostics with in-depth read-out techniques such as radiomics or novel reconstruction algorithms on pretherapeutic scans, e.g., for outcome prediction. Even 80 years after its initial clinical introduction, theranostics in oncology continues to thrive, now more than ever.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11050805
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 4
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    Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers—Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT
    MDPI AG ; 2019
    In:  Journal of Clinical Medicine Vol. 8, No. 7 ( 2019-07-19), p. 1060-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 8, No. 7 ( 2019-07-19), p. 1060-
    Abstract: The theranostic concept represents a paradigmatic example of personalized treatment. It is based on the use of radiolabeled compounds which can be applied for both diagnostic molecular imaging and subsequent treatment, using different radionuclides for labelling. Clinically relevant examples include somatostatin receptor (SSTR)-targeted imaging and therapy for the treatment of neuroendocrine tumors (NET), as well as prostate-specific membrane antigen (PSMA)-targeted imaging and therapy for the treatment of prostate cancer (PC). As such, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy using positron emission tomography (PET). While interpreting PSMA- or SSTR-targeted PET/computed tomography scans, the reader has to navigate certain pitfalls, including (I.) varying normal biodistribution between different PSMA- and SSTR-targeting PET radiotracers, (II.) varying radiotracer uptake in numerous kinds of both benign and malignant lesions, and (III.) resulting false-positive and false-negative findings. Thus, two novel reporting and data system (RADS) classifications for PSMA- and SSTR-targeted PET imaging (PSMA- and SSTR-RADS) have been recently introduced under the umbrella term molecular imaging reporting and data systems (MI-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. Learning objectives of the present case-based review are as follows: (I.) the theranostic concept for the treatment of NET and PC will be briefly introduced, (II.) the most common pitfalls on PSMA- and SSTR-targeted PET/CT will be identified, (III.) the novel framework system for theranostic radiotracers (MI-RADS) will be explained, applied to complex clinical cases and recent studies in the field will be highlighted. Finally, current treatment strategies based on MI-RADS will be proposed, which will demonstrate how such a generalizable framework system truly paves the way for clinically meaningful molecular imaging-guided treatment of either PC or NET. Thus, beyond an introduction of MI-RADS, the present review aims to provide an update of recently published studies which have further validated the concept of structured reporting systems in the field of theranostics.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm8071060
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662592-1
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  • 5
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    Generative Adversarial Networks for the Creation of Realistic Artificial Brain Magnetic Resonance Images
    MDPI AG ; 2018
    In:  Tomography Vol. 4, No. 4 ( 2018-12-01), p. 159-163
    Details
    In: Tomography, MDPI AG, Vol. 4, No. 4 ( 2018-12-01), p. 159-163
    Abstract: Even as medical data sets become more publicly accessible, most are restricted to specific medical conditions. Thus, data collection for machine learning approaches remains challenging, and synthetic data augmentation, such as generative adversarial networks (GAN), may overcome this hurdle. In the present quality control study, deep convolutional GAN (DCGAN)–based human brain magnetic resonance (MR) images were validated by blinded radiologists. In total, 96 T1-weighted brain images from 30 healthy individuals and 33 patients with cerebrovascular accident were included. A training data set was generated from the T1-weighted images and DCGAN was applied to generate additional artificial brain images. The likelihood that images were DCGAN-created versus acquired was evaluated by 5 radiologists (2 neuroradiologists [NRs], vs 3 non-neuroradiologists [NNRs] ) in a binary fashion to identify real vs created images. Images were selected randomly from the data set (variation of created images, 40%–60%). None of the investigated images was rated as unknown. Of the created images, the NRs rated 45% and 71% as real magnetic resonance imaging images (NNRs, 24%, 40%, and 44%). In contradistinction, 44% and 70% of the real images were rated as generated images by NRs (NNRs, 10%, 17%, and 27%). The accuracy for the NRs was 0.55 and 0.30 (NNRs, 0.83, 0.72, and 0.64). DCGAN-created brain MR images are similar enough to acquired MR images so as to be indistinguishable in some cases. Such an artificial intelligence algorithm may contribute to synthetic data augmentation for “data-hungry” technologies, such as supervised machine learning approaches, in various clinical applications.
    Type of Medium: Online Resource
    ISSN: 2379-139X
    URL: Article
    DOI: 10.18383/j.tom.2018.00042
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
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  • 6
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    Association of True Positivity with Serum Prostate-Specific Antigen Levels and Other Clinical Factors in Indeterminate PSMA-RADS-3A Lesions Identified on 18F-DCFPyL PET/CT Scans
    MDPI AG ; 2022
    In:  Tomography Vol. 8, No. 6 ( 2022-10-27), p. 2639-2647
    Details
    In: Tomography, MDPI AG, Vol. 8, No. 6 ( 2022-10-27), p. 2639-2647
    Abstract: The use of prostate-specific membrane antigen targeted PET imaging for the evaluation of prostate cancer has increased significantly in the last couple of decades. When evaluating these imaging findings based on the PSMA reporting and data system version 1.0, which categorize lesions based on their likelihood of prostate cancer involvement, PSMA-RADS-3A lesions are commonly seen, which are indeterminate for the presence of disease. A total of 28 patients with 171 PSMA-RADS-3A lesions on 18F-DCFPyL PET/CT scans from June 2016 to May 2017 who had follow-up cross-sectional imaging over time were included in this study. The PSA levels of patients with PSMA-RADS-3A lesions were categorized into four groups, 0–0.2, 0.2–1, 1–2, and 〉 2 ng/mL. The pre-operative Gleason score of these patients was categorized into two groups, Gleason score 〈 7 or ≥7. The median age for these patients was 72.5 years (range 59–81). The median PSA value for patients with positive lesions was significantly higher than those with negative lesions (5.8 ng/mL vs. 0.2 ng/mL, p 〈 0.0001). The lesion positivity rate was significantly higher in patients with PSA 〉 1 ng/mL (18.2% vs. 81.9%, p 〈 0.001). On ROC analysis, the highest classification accuracy was seen at PSA ≥ 0.6 ng/mL of 80.12% (95% CI = 73.69–86.16%), and the area under the curve was 71.32% (95% CI = 61.9–80.7%, p 〈 0.0001). A total of 96.4% (108/112) of patients with positive lesions and 86.4% (51/59) of patients with negative lesions had a PSMA-RADS-4/5 lymph node on the initial 18F-DCFPyL PET/CT scan (p = 0.02). In patients with a Gleason score ≥ 7, the presence of positive PSMA-RADS-3A lesions was higher, compared to negative PSMA-RADS-3A lesions (p = 0.049). Higher PSA levels in patients with PSMA-RADS-3A lesions can point towards the presence of true positivity. PSA levels may be considered in deciding whether to call an indeterminate lesion on PSMA PET.
    Type of Medium: Online Resource
    ISSN: 2379-139X
    URL: Article
    DOI: 10.3390/tomography8060220
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 7
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    CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 4 ( 2021-03-29), p. 605-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 4 ( 2021-03-29), p. 605-
    Abstract: We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer 68Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard 18F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent 18F-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. 68Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while18F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, 18F-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 68Ga-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 18F-FDG PET/CT.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11040605
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 8
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    Effect of Point-Spread Function Reconstruction for Indeterminate PSMA-RADS-3A Lesions on PSMA-Targeted PET Imaging of Men with Prostate Cancer
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 4 ( 2021-04-07), p. 665-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 4 ( 2021-04-07), p. 665-
    Abstract: Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is emerging as an important modality for imaging patients with prostate cancer (PCa). As with any imaging modality, indeterminate findings will arise. The PSMA reporting and data system (PSMA-RADS) version 1.0 codifies indeterminate soft tissue findings with the PSMA-RADS-3A moniker. We investigated the role of point-spread function (PSF) reconstructions on categorization of PSMA-RADS-3A lesions. Methods: This was a post hoc analysis of an institutional review board approved prospective trial. Around 60 min after the administration of 333 MBq (9 mCi) of PSMA-targeted 18F-DCFPyL, patients underwent PET/computed tomography (CT) acquisitions from the mid-thighs to the skull vertex. The PET data were reconstructed with and without PSF. Scans were categorized according to PSMA-RADS version 1.0, and all PSMA-RADS-3A lesions on non-PSF images were re-evaluated to determine if any could be re-categorized as PSMA-RADS-4. The maximum standardized uptake values (SUVs) of the lesions, mean SUVs of blood pool, and the ratios of those values were determined. Results: A total of 171 PSMA-RADS-3A lesions were identified in 30 patients for whom both PSF reconstructions and cross-sectional imaging follow-up were available. A total of 13/171 (7.6%) were re-categorized as PSMA-RADS-4 lesions with PSF reconstructions. A total of 112/171 (65.5%) were found on follow-up to be true positive for PCa, with all 13 of the re-categorized lesions being true positive on follow-up. The lesions that were re-categorized trended towards having higher SUVmax-lesion and SUVmax-lesion/SUVmean-blood-pool metrics, although these relationships were not statistically significant. Conclusions: The use of PSF reconstructions for 18F-DCFPyL PET can allow the appropriate re-categorization of a small number of indeterminate PSMA-RADS-3A soft tissue lesions as more definitive PSMA-RADS-4 lesions. The routine use of PSF reconstructions for PSMA-targeted PET may be of value at those sites that utilize this technology.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11040665
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 9
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    Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [177Lu]Lu-PSMA I&T
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 3 ( 2022-01-27), p. 647-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 3 ( 2022-01-27), p. 647-
    Abstract: (1) Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) has shown remarkable results in patients with advanced prostate cancer. We aimed to evaluate the toxicity profile of the PSMA ligand [177Lu]Lu-PSMA I & T. (2) Methods: 49 patients with metastatic, castration-resistant prostate cancer treated with at least three cycles of [177Lu]Lu-PSMA I & T were evaluated. Prior to and after RLT, we compared leukocytes, hemoglobin, platelet counts, and renal functional parameters (creatinine, eGFR, n = 49; [99mTc]-MAG3-derived tubular extraction rate (TER), n = 42). Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and KDIGO Society. To identify predictive factors, we used Spearman’s rank correlation coefficient. (3) Results: A substantial fraction of the patients already showed impaired renal function and reduced leukocyte counts at baseline. Under RLT, 11/49 (22%) patients presented with nephrotoxicity CTCAE I or II according to creatinine, but 33/49 (67%) according to eGFR. Only 5/42 (13%) showed reduced TER, defined as 〈 70% of the age-adjusted mean normal values. Of all renal functional parameters, absolute changes of only 2% were recorded. CTCAE-based re-categorization was infrequent, with creatinine worsening from I to II in 2/49 (4.1%; GFR, 1/49 (2%)). Similar results were recorded for KDIGO (G2 to G3a, 1/49 (2%); G3a to G3b, 2/49 (4.1%)). After three cycles, follow-up eGFR correlated negatively with age (r = −0.40, p = 0.005) and the eGFR change with Gleason score (r = −0.35, p 〈 0.05) at baseline. Leukocytopenia CTCAE II occurred only in 1/49 (2%) (CTCAE I, 20/49 (41%)) and CTCAE I thrombocytopenia in 7/49 (14%), with an absolute decrease of 15.2% and 16.6% for leukocyte and platelet counts. Anemia CTCAE II occurred in 10/49 (20%) (CTCAE I, 36/49 (73%)) with a decrease in hemoglobin of 4.7%. (4) Conclusions: After PSMA-targeted therapy using [177Lu]Lu-PSMA I & T, no severe (CTCAE III/IV) toxicities occurred, thereby demonstrating that serious adverse renal or hematological events are unlikely to be a frequent phenomenon with this agent.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14030647
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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