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Selected Papers from the 4th International Conference on Inflammation and Infection Imaging

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 (30 June 2025) | Viewed by 5963

Special Issue Editors

Prof. Dr. Alberto Signore

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Guest Editor
Nuclear Medicine Unit, University Hospital S. Andrea, “Sapienza” University of Rome, Rome, Italy
Interests: nuclear medicine; infection imaging; inflammation imaging; thyroid cancer imaging; pre-clinical imaging; imaging immuno-therapy; imaging autoimmune diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Chiara Lauri

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Guest Editor
Department of Medical-Surgical Sciences and Translational Medicine, University Hospital S. Andrea, “Sapienza” University of Rome, Rome, Italy
Interests: inflammation imaging; tumor micro-environment; personalized medicine
Dr. Michela Varani

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Guest Editor
Department of Medical-Surgical Sciences and Translational Medicine, University Hospital S. Andrea, “Sapienza” University of Rome, Rome, Italy
Interests: radiochemistry; nanotechnologies; nanoparticles; bacteria imaging

Special Issue Information

Dear Colleagues,

Following a tradition started in 1993, the 4th edition of the International Congress on "Imaging infections and inflammation" has been organized in Roma (Italy) from 5 to 7 December, 2024.

Scientific sessions included cardiovascular infections, bone infections, sterile inflammatory diseases, tumor microenvironments, and radiolabeled probes for imaging bacteria and fungi.

Each session included several lectures and roundtable discussions with the participation of several scientists and clinicians, experts in the field.

The best three oral presentations were given awards.

Since the high clinical relevance of such congress and the number and quality of studies presented, we decided to launch a Special Issue of the Journal of Clinical Medicine that could include all abstracts of congress presentations and a few selected full papers, accepted after peer review.

The early diagnosis of occult infections is a very important issue in medicine, especially for infections that do not present with obvious clinical signs but can have serious consequences if not treated promptly. The use of imaging techniques to detect hidden infections is becoming increasingly important due to their ability to visualize areas of the body that are difficult to explore, often before serious symptoms develop.

In addition to computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound, nuclear medicine techniques have improved enormously in the last decade thanks to the availability of several new radiopharmaceuticals for single-photon emission computed tomography (SPECT) and positron emission tomography (PET) use.

Rapid identification of occult infections will allow starting targeted and personalized treatment, reducing the risk of complications.

Furthermore, early diagnosis of infection in the early stages will contribute to reducing the costs of patients’ treatment with better prognoses, especially in immunocompromised patients or those with comorbidities.

One of the major challenges is the differential diagnosis between sterile inflammation and septic infection. Despite the use of radiolabeled autologous white blood cells that can allow us to differentiate inflammation from infection, the gold standard technique would be to directly image and quantify the presence of bacteria or fungi.

Another important field of application of nuclear medicine techniques is the study of tumor microenvironments. Here, by using radiopharmaceuticals that specifically target fibroblasts, lymphocytes, endothelial, or mesenchymal cells, the aim is to establish a non-invasive tool for prognostic purposes and for selecting tailored treatment.

Both fields have an enormous clinical and economic impact and will drive nuclear medicine research for the next decades.

Prof. Dr. Alberto Signore
Dr. Chiara Lauri
Dr. Michela Varani
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • infection imaging
  • inflammation imaging
  • imaging tumor micro-environment
  • bacteria imaging
  • new radiopharmaceuticals

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Published Papers (6 papers)

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Research

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15 pages, 1576 KB  
Article
A Head-to-Head Comparison Between [18F]Fluorodeoxyglucose ([18F]FDG) Positron Emission Tomography/Computed Tomography (PET/CT) and 99mTechnetium-Hexamethylpropylene Amine Oxime (HMPAO)-Labeled Leukocyte Scintigraphy in a Case Series of Patients with Suspected Vascular Prosthesis Infection: To Trust Is Good, but to Check Is Better
by Marina Scarpuzza, Alice Ambrogio, Andrea Leo, Lorenzo Roberto Suardi, Michele Marconi, Marco Falcone, Raffaella Berchiolli and Elena Lazzeri
J. Clin. Med. 2025, 14(12), 4352; https://doi.org/10.3390/jcm14124352 - 18 Jun 2025
Cited by 1 | Viewed by 695
Abstract
Background: Prosthetic vascular graft infection (PVGI) is a serious complication associated with vascular prostheses. Nuclear medicine techniques, including [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and 99mtechnetium-hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte (WBC) scintigraphy, are part of the MAGIC diagnostic criteria for [...] Read more.
Background: Prosthetic vascular graft infection (PVGI) is a serious complication associated with vascular prostheses. Nuclear medicine techniques, including [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and 99mtechnetium-hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte (WBC) scintigraphy, are part of the MAGIC diagnostic criteria for PVGI. Methods: In this retrospective study, we analyzed eight patients with suspected PVGI who underwent both [18F]FDG PET/CT and WBC scintigraphy within an average of 8 days. Results: Of all eight patients (median age 69 years), three showed concordant positive results with both PET/CT and WBC, and their final diagnosis confirmed the presence of infection; five showed discordant results: in all five of these patients, PET/CT showed false-positive findings, whereas WBC correctly identified five true-negative cases. Conclusions: [18F]FDG PET/CT is highly sensitive but prone to false positives. WBC scintigraphy, combined with SPECT/CT, particularly in the evaluation of the treatment response, showed greater specificity, and it may warrant consideration as a MAGIC major diagnostic criterion for PVGI. Full article
(This article belongs to the Special Issue Selected Papers from the 4th International Conference on Inflammation and Infection Imaging)
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14 pages, 4450 KB  
Article
Somatostatin Receptor Scintigraphy in Autoimmune Syndrome Induced by Silicone Breast Implants: Pre- and Postexplantation Findings
by Luz Kelly Anzola, Sara Ramirez, Sergio Moreno, Camilo Vargas, Sebastian Rojas and José Nelson Rivera
J. Clin. Med. 2025, 14(12), 4141; https://doi.org/10.3390/jcm14124141 - 11 Jun 2025
Viewed by 797
Abstract
Background: Silicone breast implants have been linked to autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This study evaluates the role of 99mTc-HYNIC-TOC somatostatin receptor scintigraphy in assessing somatostatin-mediated inflammation and the impact of explantation on inflammatory activity. Methods: Fifty patients with silicone breast [...] Read more.
Background: Silicone breast implants have been linked to autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This study evaluates the role of 99mTc-HYNIC-TOC somatostatin receptor scintigraphy in assessing somatostatin-mediated inflammation and the impact of explantation on inflammatory activity. Methods: Fifty patients with silicone breast implants and symptoms suggestive of ASIA were evaluated. Pre- and postexplantation imaging was performed using 99mTc-HYNIC-TOC scintigraphy. Matthews correlation coefficients quantified associations between clinical symptoms and imaging findings, and autoantibody profiles were analysed. Results: Scintigraphy identified a significant uptake in organs associated with autoimmune symptoms, particularly joints and salivary glands. Strong correlations were found between imaging findings and symptoms, including knee pain (MCC = 0.81) and sicca syndrome (MCC = 0.96). Explantation resolved abnormal uptake in the surgical bed, though variable uptake persisted in other organs, reflecting systemic inflammatory heterogeneity. Autoantibody analysis revealed positivity in 66% of patients, with antinuclear antibodies being most frequent (30%). Conclusions: 99mTc-HYNIC-TOC scintigraphy effectively evaluates organ-specific inflammation in ASIA. Explantation reduces localized inflammation but does not consistently address systemic autoimmune responses. Larger prospective studies are needed to validate these findings and improve management strategies for ASIA. Full article
(This article belongs to the Special Issue Selected Papers from the 4th International Conference on Inflammation and Infection Imaging)
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Review

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21 pages, 502 KB  
Review
A Comprehensive Review of SSTR-Based Spect and Pet Imaging in Chronic Inflammatory and Immune-Mediated Diseases
by Shaobo Li, Alex Maes, Tijl Vermassen, Justine Maes, Sylvie Rottey and Christophe Van de Wiele
J. Clin. Med. 2025, 14(23), 8451; https://doi.org/10.3390/jcm14238451 - 28 Nov 2025
Viewed by 352
Abstract
Background: Somatostatin receptors (SSTRs), especially subtype 2 (SSTR2), are increasingly recognized as valuable molecular targets in the imaging of chronic inflammatory and immune-mediated diseases. Their expression on activated immune and stromal cells enables specific, non-invasive detection of inflammatory activity using radio-labeled somatostatin analogs. [...] Read more.
Background: Somatostatin receptors (SSTRs), especially subtype 2 (SSTR2), are increasingly recognized as valuable molecular targets in the imaging of chronic inflammatory and immune-mediated diseases. Their expression on activated immune and stromal cells enables specific, non-invasive detection of inflammatory activity using radio-labeled somatostatin analogs. Objective: This review aims to summarize current evidence on SSTR-targeted imaging across a range of chronic inflammatory and immune-mediated diseases, compare its diagnostic value with 18F-FDG PET/CT, and discuss biological mechanisms, clinical applications, and remaining challenges. Methods: A literature-based narrative review was conducted, integrating preclinical studies, clinical trials, and comparative imaging research involving SSTR PET/SPECT tracers such as 68Ga-DOTATATE, 68Ga-DOTANOC, 99ᵐTc-HYNIC-TOC, and 111In-pentetreotide in diseases including vasculitis, sarcoidosis, autoimmune myocarditis, rheumatoid arthritis, and thyroid-associated ophthalmopathy. Results: SSTR-targeted imaging has shown promising specificity for inflammatory lesions and provides favorable lesion-to-background contrast, particularly in tissues with high physiological FDG uptake such as the myocardium and brain. In vasculitis and sarcoidosis, SSTR-targeted tracers may complement FDG PET by improving diagnostic confidence and inter-observer consistency in selected small studies. Mechanistically, SSTR2 expression is closely associated with cytokine-driven immune activation, predominantly involving M1 macrophages. However, current evidence remains limited by heterogeneous receptor expression, variable myocardial uptake, and the lack of standardized imaging protocols. Conclusions: SSTR-targeted molecular imaging represents a biologically grounded and clinically promising complementary approach for assessing immune-mediated inflammation. Future developments in tracer design, quantitative standardization, and multicenter clinical validation are warranted to establish its role in precision diagnostics. Full article
(This article belongs to the Special Issue Selected Papers from the 4th International Conference on Inflammation and Infection Imaging)
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24 pages, 4520 KB  
Review
Radiolabeled LHRH and FSH Analogues as Cancer Theranostic Agents: A Systematic Review
by Anna Giorgio, Michela Varani, Chiara Lauri, Valeria Bentivoglio and Pallavi Nayak
J. Clin. Med. 2025, 14(21), 7811; https://doi.org/10.3390/jcm14217811 - 3 Nov 2025
Cited by 1 | Viewed by 579
Abstract
Background: G-protein-coupled receptors (GPCRs) play pivotal roles in tumor growth and progression. Among these, the luteinizing hormone-releasing hormone receptor (LHRH-R) and follicle-stimulating hormone receptor (FSH-R) represent promising translational targets, unlike luteinizing hormone receptors (LH-Rs). Indeed, both LHRH-R and FSH-R are selectively expressed in [...] Read more.
Background: G-protein-coupled receptors (GPCRs) play pivotal roles in tumor growth and progression. Among these, the luteinizing hormone-releasing hormone receptor (LHRH-R) and follicle-stimulating hormone receptor (FSH-R) represent promising translational targets, unlike luteinizing hormone receptors (LH-Rs). Indeed, both LHRH-R and FSH-R are selectively expressed in various cancers and their vasculature, offering opportunities for receptor-mediated imaging and therapy. Objectives: This systematic review aims to evaluate radiolabeled LHRH- and FSH-derivative biomolecules, including peptides, monoclonal antibodies and nanocarriers, for their applications in cancer diagnosis and treatment. Methods: The systematic review was conducted following PRISMA 2020 guidelines. A systematic search of PubMed, Scopus and Web of Science was conducted for studies published between 2005 and 2025. A total of 248 records were identified, and 156 articles were screened after removing duplicate records. Two authors independently selected eligible studies. Quality of evidence was assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) approach. Results: A total of 25 studies met the inclusion criteria and were included in the final review. Radiolabeled LHRH and FSH derivatives showed receptor-specific tumor localization in both preclinical and clinical applications. FSH-R expression in tumor blood vessels supports its potential as a biomarker for early cancer diagnosis. FSHβ-derived peptides exhibit improved pharmacokinetics compared to monoclonal antibodies in PET imaging. LHRH analogues, particularly D-Lys6-modified peptides, proved effective for SPECT, PET and therapeutic applications, particularly in breast and prostate cancer. The integration of radiolabeled LHRH and FSH derivatives with nanocarriers further enhanced probe stability and tumor targeting, increasing tumor accumulation and image contrast compared to free peptide. Conclusions: Radiopharmaceuticals targeting LHRH-R and FSH-R are promising tools for cancer imaging and treatment. Advances in nanotechnology enhance delivery precision and reduce systemic toxicity, thereby increasing its translational promise in oncology. Full article
(This article belongs to the Special Issue Selected Papers from the 4th International Conference on Inflammation and Infection Imaging)
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12 pages, 281 KB  
Review
Role of 18F FDG-PET-CT in Fever and Inflammation of Unknown Origin
by Elena Romano Gargarella, Flaminia Vocaturo, Andrea Guarneri, Maria Lucia Calcagni and Lucia Leccisotti
J. Clin. Med. 2025, 14(16), 5861; https://doi.org/10.3390/jcm14165861 - 19 Aug 2025
Cited by 1 | Viewed by 2107
Abstract
Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) remain complex diagnostic challenges due to their heterogeneous presentations and broad differential diagnoses. FUO was first described by Petersdorf and Beeson in 1961 and later redefined by Durack and Street, while IUO [...] Read more.
Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) remain complex diagnostic challenges due to their heterogeneous presentations and broad differential diagnoses. FUO was first described by Petersdorf and Beeson in 1961 and later redefined by Durack and Street, while IUO was introduced more recently by Vanderschueren et al. in 2009. Despite thorough investigations, a significant proportion of patients remain without a clear diagnosis, often resulting in prolonged hospital stays and increased healthcare costs. In recent years, [18F]FDG PET/CT has emerged as a valuable tool in the diagnostic workup of FUO and IUO, offering both metabolic and anatomical insights in a single scan. This review evaluates the diagnostic utility of [18F]FDG PET/CT, based on an analysis of 55 studies encompassing 6681 patients. The scan was found to be clinically helpful in 59% of cases, with diagnostic contributions from both true-positive and true-negative findings. Negative scans were frequently associated with spontaneous symptom resolution and fewer unnecessary interventions. However, differences in study design and definitions of diagnostic value make it difficult to compare results across studies. Overall, [18F]FDG PET/CT has proven to be a useful tool in the evaluation of FUO and IUO, and future research should focus on standardizing how its clinical benefit is measured and directly comparing its effectiveness with conventional imaging in well-designed prospective studies. Full article
(This article belongs to the Special Issue Selected Papers from the 4th International Conference on Inflammation and Infection Imaging)
11 pages, 251 KB  
Review
PET and SPECT Imaging of Macrophages in the Tumor Stroma: An Update
by Shaobo Li, Alex Maes, Tijl Vermassen, Justine Maes, Chabi Sathekge, Sylvie Rottey and Christophe Van de Wiele
J. Clin. Med. 2025, 14(14), 5075; https://doi.org/10.3390/jcm14145075 - 17 Jul 2025
Viewed by 1121
Abstract
Tumor-associated macrophages (TAMs) are pivotal immune cells within the tumor stroma, whose dynamic alterations significantly impact tumor progression and therapeutic responses. Conventional methods for TAM detection, such as biopsy, are invasive and incapable of whole-body dynamic monitoring. In contrast, positron emission tomography (PET) [...] Read more.
Tumor-associated macrophages (TAMs) are pivotal immune cells within the tumor stroma, whose dynamic alterations significantly impact tumor progression and therapeutic responses. Conventional methods for TAM detection, such as biopsy, are invasive and incapable of whole-body dynamic monitoring. In contrast, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) offer a non-invasive imaging approach by targeting TAM-specific biomarkers like CD206, TSPO, and CCR2. This review comprehensively summarizes the advancements in TAM-targeted imaging probes, including cell surface markers, metabolic/functional markers, and multifunctional nanoprobe, while assessing their potential in tumor immune surveillance and tumor targeting therapeutic applications. While current probes, including 68Ga-NOTA-anti-CD206 and 64Cu-Macrin, have exhibited high specificity and theragnostic potential in preclinical and early clinical trials, challenges such as target heterogeneity, off-target effects, and clinical translation persist. Moving forward, the advancement of multi-target probes, optimization of pharmacokinetics, and incorporation of multimodal imaging technologies are anticipated to further enhance the impact of TAM-targeted imaging in precision medicine and tumor immunotherapy, fostering the refinement of personalized treatment strategies and improving patient outcomes. Full article
(This article belongs to the Special Issue Selected Papers from the 4th International Conference on Inflammation and Infection Imaging)
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