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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nuclear Medicine & Radiology".

Deadline for manuscript submissions: closed (20 June 2019) | Viewed by 42226

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Dr. Constantin Lapa

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Guest Editor

Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
Interests: multiple myeloma; novel PET tracers; theranostics; radionuclide therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nuclear medicine has experienced a number of unprecedented developments in recent years. Above all, the concept of "theranostics", the combination of a predictive biomarker with a therapeutic agent, has been a central part of this success. For example, a phase III randomized, controlled trial provided unequivocal evidence of the effectiveness of 177Lu-DOTATATE for treatment of neuroendocrine tumors, and there have been multiple reports of the benefits of prostate-specific membrane antigen targeted PET imaging and radio-ligand therapy in prostate cancer. Other new exciting theranostic applications include, among many others, C-X-C motif chemokine receptor 4, as well as cancer-associated fibroblasts. These can be specifically addressed by inhibitors of the fibroblast activation protein and represent a particularly promising target for nuclear medicine theranostics. This Special Issue aims to present the most recent advances in the field of nuclear medicine imaging and therapy, as well as their implications for future patient care.

Dr. Constantin Lapa
Guest Editor

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Keywords

PET
Theranostics
PSMA
SSTR
CXCR4
FAP
Radio-ligand therapy
Nuclear medicine

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

3 pages, 147 KiB

Open AccessEditorial

Exciting Opportunities in Nuclear Medicine Imaging and Therapy

by Constantin Lapa

J. Clin. Med. 2019, 8(11), 1944; https://doi.org/10.3390/jcm8111944 - 12 Nov 2019

Cited by 2 | Viewed by 2198

Abstract

Nuclear medicine has experienced a number of unprecedented developments in recent years. Above all, the concept of “theranostics”, the combination of a predictive biomarker with a therapeutic agent, has been a central part of this success. For example, a phase III randomized, controlled trial provided unequivocal evidence of the effectiveness of 177Lu-DOTATATE for treatment of neuroendocrine tumors, and there have been multiple reports of the benefits of prostate-specific membrane antigen targeted PET imaging and radio-ligand therapy in prostate cancer. Other new exciting theranostic applications include, among many others, C-X-C motif chemokine receptor 4, as well as cancer-associated fibroblasts. These can be specifically addressed by inhibitors of the fibroblast activation protein and represent a particularly promising target for nuclear medicine theranostics. This Special Issue presents some of the most recent advances in the field of nuclear medicine. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

Research

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14 pages, 4883 KiB

Open AccessArticle

Effect of F-18 Fluorodeoxyglucose Uptake by Bone Marrow on the Prognosis of Head and Neck Squamous Cell Carcinoma

by Jeong Won Lee, Myung Jin Ban, Jae Hong Park and Sang Mi Lee

J. Clin. Med. 2019, 8(8), 1169; https://doi.org/10.3390/jcm8081169 - 4 Aug 2019

Cited by 15 | Viewed by 4687

Abstract

The purpose of this study was to assess the relationship between F-18 fluorodeoxyglucose (FDG) uptake in bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) and survival in patients with head and neck squamous cell carcinoma (HNSCC). We retrospectively enrolled 157 HNSCC patients who underwent staging FDG PET/CT and subsequent treatment. On PET/CT, primary tumor metabolic characteristics, mean FDG uptake of BM (BM SUV), and BM-to-liver uptake ratio (BLR) were measured. The prognostic significance of FDG uptake of BM for predicting disease progression-free survival and distant failure-free survival was assessed using a Cox proportional hazards regression model. In univariate analysis for disease progression-free survival, increased BM SUV and BLR were associated with poor survival. In multivariate analysis, BLR (p = 0.044; hazard ratio, 1.96), TNM stage (p = 0.014; hazard ratio, 2.87) and maximum FDG uptake of the primary tumor (p = 0.046; hazard ratio, 2.38) were independently associated with disease progression-free survival. For distant failure-free survival, BLR, TNM stage, tumor size, and metabolic parameters of the primary tumor showed prognostic significance in univariate analysis. However, none of the variables showed significance in multivariate analysis. FDG uptake of BM in HNSCC patients might be a significant predictor for disease progression-free survival. Further studies with large patient population are needed to validate the results. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

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12 pages, 2165 KiB

Open AccessArticle

Hybrid Imaging in Head and Neck Sarcoidosis

by Isidora Grozdic Milojevic, Marijana Tadic, Dragana Sobic-Saranovic, Jelena Saponjski and Vera M. Artiko

J. Clin. Med. 2019, 8(6), 803; https://doi.org/10.3390/jcm8060803 - 5 Jun 2019

Cited by 2 | Viewed by 3023

Abstract

To determine the prevalence of head and neck sarcoidosis (HNS) and evaluate the role of hybrid molecular imaging in HNS. Between 2010 and 2018, 222 patients with chronic sarcoidosis and presence of prolonged symptoms of active disease were referred to FDG PET/CT. Active disease was found in 169 patients, and they were all screened for the presence of HNS. All patients underwent MDCT and assessment of the serum ACE level. Follow-up FDG PET/CT examination was done 19.84 ± 8.98 months after the baseline. HNS was present in 38 out of 169 patients. FDG uptake was present in: cervical lymph nodes (38/38), submandibular glands (2/38), cerebrum (2/38), and bone (1/38). The majority of patients had more than two locations of disease. After FDG PET/CT examination, therapy was changed in most patients. Fourteen patients returned to follow-up FDG PET/CT examination in order to assess the therapy response. PET/CT revealed active disease in 12 patients and complete remission in two patients. Follow-up ACE levels had no correlation with follow-up SUVmax level (ρ = −0.18, p = 0.77). FDG PET/CT can be useful in the detection of HNS and in the evaluation of the therapy response. It may replace the use of non-purposive mounds of insufficiently informative laboratory and radiological procedures. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

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11 pages, 1560 KiB

Open AccessArticle

Value of Somatostatin Receptor Scintigraphy with ^99mTc-HYNIC-TOC in Patients with Primary Sjögren Syndrome

by Luz Kelly Anzola, Josè Nelson Rivera, Rudi A. Dierckx, Chiara Lauri, Stefano Valabrega, Filippo Galli, Sergio Moreno Lopez, Andor W. J. M. Glaudemans and Alberto Signore

J. Clin. Med. 2019, 8(6), 763; https://doi.org/10.3390/jcm8060763 - 30 May 2019

Cited by 22 | Viewed by 3419

Abstract

Objectives: Primary Sjögren syndrome (SS) is diagnosed based on the American European Consensus Group (AECG) criteria, but lacks specificity, not only in the involvement of salivary glands, but also in extra-glandular involvement. Whole-body somatostatin receptor scintigraphy with ^99mTc-HYNIC-TOC scintigraphy could overcome these limitations. The aims of this study were to evaluate salivary gland uptake of ^99mTc-HYNIC-TOC in untreated patients with de-novo diagnosis of SS as compared to control subjects and as compared to conventional sialoscintigraphy with ^99mTcO₄⁻. We also aimed to evaluate the involvement of joints. Methods: ^99mTc-HYNIC-TOC was used with SS patients and uptake in joints and salivary glands was analyzed semi-quantitatively. Patients also underwent ^99mTcO₄ sialoscintigraphy. The control group that we analyzed consisted of 30 patients with neuroendocrine tumors. Results: Fifty-two females and 10 males fully met the AECG criteria for SS, and were included. A target background ratio (TBR) >1.18 in submandibular glands correctly classified 93% of the patients with SS in comparison to 27% for ^99mTcO₄ sialoscintigraphy. The area under the curve (ROC) analysis for TBR in submandibular glands was 0.95. In joints there was a huge variety in uptake. The median TBR was significantly higher in salivary glands in patients with SS compared to controls. Conclusions: ^99mTc-HYNIC-TOC scintigraphy identified active inflammatory processes not only in the salivary glands, but, unexpectedly, also in many joints in patients with primary SS, contrary to popular belief. This technique provides an objective parameter to evaluate the inflammation burden in salivary glands and joints and could be used to evaluate response to treatment. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

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20 pages, 5519 KiB

Open AccessArticle

Selection Criteria for Determination of Optimal Reconstruction Method for Cu-64 Trastuzumab Dosimetry on Siemens Inveon PET Scanner

by Seonhwa Lee, Hyeongi Kim, Ye-rin Kang, Hyungwoo Kim, Jung Young Kim, Yong-Jin Lee, Jung Min Kim and Jin Su Kim

J. Clin. Med. 2019, 8(4), 512; https://doi.org/10.3390/jcm8040512 - 14 Apr 2019

Cited by 4 | Viewed by 3249

Abstract

The goal of this study was to suggest criteria for the determination of the optimal image reconstruction algorithm for image-based dosimetry of Cu-64 trastuzumab PET in a mouse model. Image qualities, such as recovery coefficient (RC), spill-over ratio (SOR), and non-uniformity (NU), were [...] Read more.

200 {mm}^{3}

, HER2 NCI N87) were injected with monoclonal antibodies (trastuzumab) with Cu-64. Preclinical mouse PET images were acquired at 4 time points after injection (2, 15, 40 and 64 h). Phantom and Cu-64 trastuzumab PET images were reconstructed using various reconstruction algorithms (filtered back projection (FBP), 3D reprojection algorithm (FBP-3DRP), 2D ordered subset expectation maximization (OSEM 2D), and OSEM 3D maximum a posteriori (OSEM3D-MAP)) and filters. The absorbed dose for the tumor and the effective dose for organs for Cu-64 trastuzumab PET were calculated using the OLINDA/EXM program with various reconstruction algorithms. Absorbed dose for the tumor ranged from 923 mGy/MBq to 1830 mGy/MBq with application of reconstruction algorithms and filters. When OSEM2D was used, the effective osteogenic dose increased from 0.0031 to 0.0245 with an increase in the iteration number (1 to 10). In the region of kidney, the effective dose increased from 0.1870 to 1.4100 when OSEM2D was used with iteration number 1 to 10. To determine the optimal reconstruction algorithms and filters, a correlation between RC and NU was plotted and selection criteria (0.9 < RC < 1.0 and < 10% of NU) were suggested. According to the selection criteria, OSEM2D (iteration 1) was chosen for the optimal reconstruction algorithm. OSEM2D (iteration 10) provided 154.7% overestimated effective dose and FBP with a Butterworth filter provided 20.9% underestimated effective dose. We suggested OSEM2D (iteration 1) for the calculation of the effective dose of Cu-64 trastuzumab on an Inveon PET scanner. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

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11 pages, 983 KiB

Open AccessArticle

Diffusely Increased ¹⁸F-FDG Uptake in the Thyroid Gland and Risk of Thyroid Dysfunction: A Cohort Study

by Young Hwan Kim, Yoosoo Chang, Yejin Kim, Soo Jeong Kim, Eun-Jung Rhee, Hyemi Kwon, Jiin Ahn and Seungho Ryu

J. Clin. Med. 2019, 8(4), 443; https://doi.org/10.3390/jcm8040443 - 2 Apr 2019

Cited by 11 | Viewed by 4719

Abstract

The impact of incidentally identified diffuse thyroid FDG uptake on ¹⁸F-FDG PET/CT scan on the incidence of thyroid dysfunction remains unclear. We examined the association of diffuse thyroid FDG uptake with the development of thyroid dysfunction. This cohort study involved 39,098 Korean adults who were free of malignancy and thyroid disease at baseline and underwent regular health checkup examinations including an ¹⁸F-FDG whole body PET/CT scan, thyroid-stimulating hormone and free thyroxine. The participants were annually or biennially followed for up to 5 years. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Diffuse thyroid uptake was positively associated with increased risk of thyroid dysfunction in both the cross-sectional and cohort studies. During 104,261.4 person-years of follow-up, 102 incident hypothyroidism cases and 172 hyperthyroidism cases were identified. Multivariable-adjusted HR (95% CI) for incident hypothyroidism or hyperthyroidism comparing diffuse thyroid uptake to no uptake were 15.72 (9.23–26.77) and 7.38 (4.23–12.87), respectively. In this large cohort, incidentally, identified diffuse thyroid uptake on ¹⁸F-FDG PET/CT was associated with increased risk of both prevalent and incident thyroid dysfunction. Therefore, baseline and follow-up evaluations in individuals with diffuse thyroid uptake may help identify individuals with thyroid dysfunction. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

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Review

Jump to: Editorial, Research

17 pages, 2798 KiB

Open AccessReview

The Roles of Hypoxia Imaging Using ¹⁸F-Fluoromisonidazole Positron Emission Tomography in Glioma Treatment

by Kenji Hirata, Shigeru Yamaguchi, Tohru Shiga, Yuji Kuge and Nagara Tamaki

J. Clin. Med. 2019, 8(8), 1088; https://doi.org/10.3390/jcm8081088 - 24 Jul 2019

Cited by 38 | Viewed by 5491

Abstract

Glioma is the most common malignant brain tumor. Hypoxia is closely related to the malignancy of gliomas, and positron emission tomography (PET) can noninvasively visualize the degree and the expansion of hypoxia. Currently, ¹⁸F-fluoromisonidazole (FMISO) is the most common radiotracer for hypoxia imaging. The clinical usefulness of FMISO PET has been established; it can distinguish glioblastomas from lower-grade gliomas and can predict the microenvironment of a tumor, including necrosis, vascularization, and permeability. FMISO PET provides prognostic information, including survival and treatment response information. Because hypoxia decreases a tumor’s sensitivity to radiation therapy, dose escalation to an FMISO-positive volume is an attractive strategy. Although this idea is not new, an insufficient amount of evidence has been obtained regarding this concept. New tracers for hypoxia imaging such as ¹⁸F-DiFA are being tested. In the future, hypoxia imaging will play an important role in glioma management. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

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19 pages, 6535 KiB

Open AccessReview

Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers—Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT

by Rudolf A. Werner, James T. Thackeray, Martin G. Pomper, Frank M. Bengel, Michael A. Gorin, Thorsten Derlin and Steven P. Rowe

J. Clin. Med. 2019, 8(7), 1060; https://doi.org/10.3390/jcm8071060 - 19 Jul 2019

Cited by 20 | Viewed by 8624

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. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

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26 pages, 740 KiB

Open AccessReview

PET Radiopharmaceuticals for Specific Bacteria Imaging: A Systematic Review

by Sveva Auletta, Michela Varani, Rika Horvat, Filippo Galli, Alberto Signore and Søren Hess

J. Clin. Med. 2019, 8(2), 197; https://doi.org/10.3390/jcm8020197 - 6 Feb 2019

Cited by 53 | Viewed by 5356

Abstract

Background: Bacterial infections are still one of the main factors associated with mortality worldwide. Many radiopharmaceuticals were developed for bacterial imaging, both with single photon emission computed tomography (SPECT) and positron emission tomography (PET) isotopes. This review focuses on PET radiopharmaceuticals, performing a systematic literature review of published studies between 2005 and 2018. Methods: A systematic review of published studies between 2005 and 2018 was performed. A team of reviewers independently screened for eligible studies. Because of differences between studies, we pooled the data where possible, otherwise, we described separately. Quality of evidence was assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS) approach. Results: Eligible papers included 35 published studies. Because of the heterogeneity of animal models and bacterial strains, we classified studies in relation to the type of bacterium: Gram-positive, Gram-negative, Gram-positive and negative, others. Conclusions: Results highlighted the availability of many promising PET radiopharmaceuticals for bacterial imaging, despite some bias related to animal selection and index test, but few have been translated to human subjects. Results showed a lack of standardized infection models and experimental settings. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

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