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Diagnostics
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Applications of PET/CT in Clinical Diagnostics
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Applications of PET/CT in Clinical Diagnostics

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Medical Imaging and Theranostics".

Deadline for manuscript submissions: closed (13 November 2025) | Viewed by 19838

Special Issue Editors

Prof. Dr. Jasna M. Mihailovic

E-Mail Website
Guest Editor
Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Interests: PET/CT imaging; thyroid cancer; radionuclide diagnostics; radionuclide treatment
Special Issues, Collections and Topics in MDPI journals
Dr. Partha S Choudhury

E-Mail Website
Guest Editor
Rajiv Gandhi Cancer Institute & Research Centre Delhi, New Delhi, India
Interests: molecular imaging; theranostics; tracers beyond FDG

Special Issue Information

Dear Colleagues,

Positron emission tomography/computed tomography (PET/CT), a fused imaging tool, efficiently combines functional (metabolic) and anatomical (morphologic) information simultaneously. The most frequently used radiotracer for PET/CT imaging is deoxy-2-[18 F] fluoro-D-glucose (F-18 FDG), a glucose analog with a fluorine isotope (F-18) replacing the hydroxyl group. This radiotracer shows increased uptake in tumor cells due to increased anaerobic glycolysis (Warburg effect). The F-18 FDG PET/CT, with its unique ability to highlight tumor cells, plays a pivotal role in clinical diagnostics in oncology. It is a milestone of neoplasm diagnostic algorithms for detection, staging, treatment response evaluation, restaging, and prognosis.

In addition to PET CT using 18-F FDG, which is the workhorse in day-to-day practice, multiple other tracers have been developed and are used routinely. A few examples of these tracers are F-18 Fluoroestradiol (FES) which is used to image ER +ve breast cancer, Ga-68 DOTANOC/DOTATOC, used to image SSTR receptors, Ga-68/F-18 PSMA used in prostate cancer, and the most recent example, -68 FAPI, which images the tumour microenvironment. Unlike 18-F FDG, which looks into the glucose utilisation in various tumours, each of these above-mentioned radiopharmaceuticals look into the specific aspects in various tumours and can be used in detection, staging, response evaluation, restaging and prognostication.

Prof. Dr. Jasna M. Mihailovic
Dr. Partha S Choudhury
Guest Editors

Manuscript Submission Information

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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

  • F-18
  • fluorodeoxyglucose
  • PET/CT imaging
  • oncology
  • radiotracers beyond F-18 fluorodeoxyglucose
  • clinical diagnostics

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Published Papers (6 papers)

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Research

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13 pages, 1291 KB  
Article
Standard Visual and Ordinal Coronary Calcium Scoring on PET/CT: Agreement with Agatston Scoring and Prognostic Implications
by Sehyun Pak, Hye Joo Son, Dongwoo Kim, Jung Won Moon, Yoo Na Kim, Ji Young Woo, Min-Kyung Kang, Dong-Ok Won and Suk Hyun Lee
Diagnostics 2025, 15(23), 2969; https://doi.org/10.3390/diagnostics15232969 - 22 Nov 2025
Viewed by 1385
Abstract
Background: Visual assessment of coronary artery calcium (CAC) on ungated chest CT has been described previously. However, its reliability and clinical utility remain uncertain, particularly in PET/CT studies that use low-dose, low-slice CT and are susceptible to respiratory artifacts. Methods: We [...] Read more.
Background: Visual assessment of coronary artery calcium (CAC) on ungated chest CT has been described previously. However, its reliability and clinical utility remain uncertain, particularly in PET/CT studies that use low-dose, low-slice CT and are susceptible to respiratory artifacts. Methods: We retrospectively analyzed 106 patients (median age, 66 years [interquartile range, 60–75 years]; 67 men [63.2%]) who underwent PET/CT and electrocardiogram (ECG)-gated chest CT within a 90-day interval. Six readers (three radiologists and three nuclear medicine physicians) independently assessed CAC on PET/CT using a standard four-point visual scale and a 0–12 ordinal scale based solely on written instructions. Agatston scoring was also performed. Interobserver agreement and concordance with ECG-gated chest CT Agatston score categories were calculated. Major adverse cardiovascular events (MACE) were recorded over a median follow-up of 3.5 years. Results: Interobserver agreement was good for both the standard visual (κ = 0.761) and ordinal (κ = 0.779) scales. Concordance with ECG-gated CT Agatston categories was higher for standard visual (κ = 0.849) and ordinal (κ = 0.750) scoring than for PET/CT Agatston categories (κ = 0.464). Both qualitative scales tended to underestimate CAC categories compared with ECG-gated CT; however, severe CAC on PET/CT predicted MACE (hazard ratios: 4.41 standard visual; 6.59 ordinal), and the ordinal scale significantly stratified MACE-free survival (p = 0.047). Conclusions: Standard visual and ordinal CAC scoring on the ungated CT portion of PET/CT is quick, reproducible, closely mirrors ECG-gated-CT Agatston grading, and offers prognostic value for future MACE in cancer patients. Full article
(This article belongs to the Special Issue Applications of PET/CT in Clinical Diagnostics)
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15 pages, 1645 KB  
Article
Total Lesion Glycolysis (TLG) on 18F-FDG PET/CT as a Potential Predictor of Pathological Complete Response in Locally Advanced Rectal Cancer After Total Neoadjuvant Therapy: A Retrospective Study
by Handan Tokmak, Nurhan Demir and Hazal Cansu Çulpan
Diagnostics 2025, 15(14), 1800; https://doi.org/10.3390/diagnostics15141800 - 16 Jul 2025
Cited by 2 | Viewed by 1894
Abstract
Background: The accurate prediction of pathological complete response (pCR) following total neoadjuvant therapy (TNT) is crucial for optimising treatment protocols in locally advanced rectal cancer (LARC). Although conventional imaging techniques such as MRI show limitations in assessing treatment response, metabolic imaging utilising 18F-fluorodeoxyglucose [...] Read more.
Background: The accurate prediction of pathological complete response (pCR) following total neoadjuvant therapy (TNT) is crucial for optimising treatment protocols in locally advanced rectal cancer (LARC). Although conventional imaging techniques such as MRI show limitations in assessing treatment response, metabolic imaging utilising 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) provides distinctive information by quantifying tumour glycolytic activity. This study investigates the predictive value of sequential 18F-FDG PET-CT parameters, focusing on Total Lesion Glycolysis (TLG), in predicting pCR after TNT. Methods: We conducted a retrospective analysis of 33 LARC patients (T3–4/N0–1) treated with TNT (neoadjuvant-chemoradiation followed by consolidation FOLFOX chemotherapy). Sequential PET-CT scans were performed at baseline, interim (after 4 cycles of FOLFOX), and post-TNT. Metabolic parameters, including maximum standardised uptake value (SUVmax) and TLG, were measured. Receiver operating characteristic (ROC) analysis assessed the predictive performance of these parameters for pCR. Results: The pCR rate was 21.2% (7/33). Post-TNT TLG ≤ 10 demonstrated excellent predictive accuracy for pCR (AUC 0.887, 92.3% sensitivity, 85.7% specificity, and 96.0% PPV), outperforming SUVmax (AUC 0.843). Interim TLG ≤ 10 also showed a strong predictive value (AUC 0.824, 100% sensitivity, and 71.4% specificity). Conclusions: TLG may serve as a reliable metabolic biomarker for predicting pathologic complete response (pCR) after total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC). Its inclusion in clinical decision-making could improve patient selection for organ preservation strategies, thereby reducing the need for unnecessary surgeries in the future. However, given that the study is based on a small retrospective design, the findings should be interpreted with caution and used alongside other decision-making tools until more comprehensive data are collected from larger studies. Full article
(This article belongs to the Special Issue Applications of PET/CT in Clinical Diagnostics)
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14 pages, 586 KB  
Article
[18F]-FDG PET-CT in Malignant Melanoma
by Teodora Sidonia Mititelu, Mihaela Raluca Mititelu, Sandica Bucurica and Daniel Octavian Costache
Diagnostics 2025, 15(10), 1192; https://doi.org/10.3390/diagnostics15101192 - 8 May 2025
Cited by 1 | Viewed by 1931
Abstract
Background/Objectives: Malignant melanoma (MM) is an aggressive neoplasm with a rising global incidence. Accurate staging and risk stratification are essential for guiding therapeutic decisions and improving patient prognosis. [18F]-FDG PET-CT enables the non-invasive assessment of tumor metabolic activity, offering a valuable adjunct [...] Read more.
Background/Objectives: Malignant melanoma (MM) is an aggressive neoplasm with a rising global incidence. Accurate staging and risk stratification are essential for guiding therapeutic decisions and improving patient prognosis. [18F]-FDG PET-CT enables the non-invasive assessment of tumor metabolic activity, offering a valuable adjunct to histopathological evaluation. However, the correlation between PET-CT findings and established prognostic markers in MM, such as Breslow thickness, ulceration, and mitotic rate, remains insufficiently explored. Methods: This retrospective observational study included 61 patients diagnosed with MM, of whom 48 met the inclusion criteria. Quantitative and qualitative variables such as SULmax, Breslow thickness, Ki-67 expression, and mitotic rate were analyzed using descriptive statistics, while correlations between PET-CT findings, SLNB, and histopathological characteristics were assessed using Spearman’s correlation test. A p-value < 0.05 was considered statistically significant. Results: Significant associations were identified between ulceration and both overall metastases (p = 0.01) and pulmonary metastases (p = 0.02). Breslow thickness showed a positive correlation with metastatic spread (p = 0.01), reinforcing its role as a key prognostic indicator. Perineural and vascular invasion were significantly associated with intra-abdominal metastases (p < 0.001 and p = 0.0007, respectively). Tumor-infiltrating lymphocytes (TILs) were inversely correlated with intra-abdominal metastases (p = 0.05), while sentinel lymph node positivity correlated with the presence of regional (p = 0.008) and distant (p = 0.02) metastases. Additionally, subcutaneous SULmax values were significantly higher in male patients compared to females (p = 0.04). Conclusions: Integrating PET-CT metabolic parameters with histopathological markers enhances the assessment of MM aggressiveness and metastatic potential. By refining risk stratification, PET-CT may contribute to personalized therapeutic strategies and improved patient management in MM. Full article
(This article belongs to the Special Issue Applications of PET/CT in Clinical Diagnostics)
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Review

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18 pages, 2930 KB  
Review
The Role of Nuclear Medicine in Prostate Cancer
by Isidora Grozdic Milojevic, Bogomir Milojevic, Daniel Skrijelj, Uros Bumbasirevic, Aleksandar Janicic, Boris Kajmakovic, Dragana Sobic-Saranovic, Vera Artiko and Slobodanka Beatovic
Diagnostics 2025, 15(22), 2876; https://doi.org/10.3390/diagnostics15222876 - 13 Nov 2025
Cited by 1 | Viewed by 1447
Abstract
Background: Considering the high global frequency of prostate cancer, it is necessary to know the benefits and drawbacks of numerous diagnostic and therapeutic modalities. Methods: In this article, we include 88 manuscripts (46/88 original studies) found on PubMed, written in English [...] Read more.
Background: Considering the high global frequency of prostate cancer, it is necessary to know the benefits and drawbacks of numerous diagnostic and therapeutic modalities. Methods: In this article, we include 88 manuscripts (46/88 original studies) found on PubMed, written in English in extenso, dealing with nuclear medicine methods in patients with prostate cancer. Results: Choline PET/CT had low sensitivity in detecting the primary tumor. This method has been almost completely replaced by PSMA PET/CT, which is included in international guidelines and recommended for initial staging of unfavorable intermediate- to high-risk prostate cancer, the detection of recurrent disease after treatment, the evaluation of mCRPC, therapy response evaluation, and theranostics. FDG is currently used in aggressive forms of prostate cancer and as a supplement in PSMA PET/CT for patient selection for RLT. Na[18F]F has demonstrated satisfactory diagnostic capacity for evaluating bone loss; however, due to a lack of research, it is not recommended in international guidelines. 18F-Fluciclovine has lower sensitivity than [18F]F-PSMA-1007 for the detection of early biochemical recurrence in prostate cancer. GRPR and SSTR analogs are less frequently used but can be useful in the evaluation of rarer pathohistological types. [99mTc]Tc-PSMA can be used in resource-limited settings where PET/CT is unavailable, with a lower sensitivity compared to [18F]F-PSMA-1007 but a higher sensitivity compared to bone scans. Conclusions: PSMA tracers are important tools for evaluating intermediate- and high-risk prostate cancer, with limitations in 5–10% of prostate cancers that do not express PSMA. Theranostics are increasingly incorporating PSMA. Full article
(This article belongs to the Special Issue Applications of PET/CT in Clinical Diagnostics)
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29 pages, 770 KB  
Review
Evolving Paradigm in Radioactive Iodine Therapy for Differentiated Thyroid Cancer: Historical Perspectives, Current Practices and Future Directions
by Jasna Mihailović
Diagnostics 2025, 15(11), 1438; https://doi.org/10.3390/diagnostics15111438 - 5 Jun 2025
Cited by 5 | Viewed by 10766
Abstract
Therapy with radioactive iodine (I-131) following a total thyroidectomy has been a gold standard in the treatment of differentiated thyroid cancer (DTC) for over 80 years. Over the years, its role has shifted from routine use to a more selective, risk-adapted approach, informed [...] Read more.
Therapy with radioactive iodine (I-131) following a total thyroidectomy has been a gold standard in the treatment of differentiated thyroid cancer (DTC) for over 80 years. Over the years, its role has shifted from routine use to a more selective, risk-adapted approach, informed by tumor biology, patient risk stratification and evolving clinical guidelines. This review examines the changing landscape of I-131 therapy, tracing its historical foundations, current indications, and future directions shaped by molecular medicine. We discuss the transition from a standardized, one-size-fits-all treatment approach to an individualized, dynamic stratification model that allows for ongoing risk reassessment and tailored treatment strategies. Key updates in clinical practice, such as the 2015 ATA Guidelines, the 2022 ETA Consensus Statement, and joint SNMMI and EANM nuclear medicine recommendations, are critically examined. We also address ongoing controversies in the management of low- and intermediate-risk patients, including the roles of I-131 whole-body scanning, activity selection, and overall treatment approach. Molecular theranostics is ushering in a new era in DTC management, enabling improved patient selection and more precise treatment. Advances in molecular profiling, imaging, and targeted therapies support a personalized treatment approach that aims to optimize therapeutic decisions while minimizing side effects and enhancing long-term safety. Full article
(This article belongs to the Special Issue Applications of PET/CT in Clinical Diagnostics)
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Other

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22 pages, 4931 KB  
Systematic Review
Advancements in Renal Imaging: A Comprehensive Systematic Review of PET Probes for Enhanced GFR and Renal Perfusion Assessment
by Marwah Abdulrahman, Ahmed Saad Abdlkadir, Serin Moghrabi, Salem Alyazjeen, Soud Al-Qasem, Deya’ Aldeen Sulaiman Sweedat, Saad Ruzzeh, Dragi Stanimirović, Michael C. Kreissl, Hongcheng Shi, Mike Sathekge and Akram Al-Ibraheem
Diagnostics 2025, 15(24), 3209; https://doi.org/10.3390/diagnostics15243209 - 15 Dec 2025
Viewed by 1515
Abstract
Glomerular filtration rate (GFR) is a key indicator of renal function. Traditional methods for GFR measurement have limitations including invasiveness, low spatial resolution, and lengthy protocols. Positron emission tomography (PET) radiotracers have emerged as promising tools for non-invasive, accurate, and dynamic renal function [...] Read more.
Glomerular filtration rate (GFR) is a key indicator of renal function. Traditional methods for GFR measurement have limitations including invasiveness, low spatial resolution, and lengthy protocols. Positron emission tomography (PET) radiotracers have emerged as promising tools for non-invasive, accurate, and dynamic renal function assessment. Objectives: This systematic literature review evaluates the clinical utility, and current evidence surrounding PET radiotracers used for GFR measurement in humans, emphasizing advances over conventional renal imaging modalities. Methods: A systematic literature search was conducted in PubMed, Web of Science, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, from database inception to November 2024. The search identified studies evaluating PET-based measurement of glomerular filtration rate (GFR) and renal perfusion. Inclusion criteria encompassed human studies using PET radiotracers (e.g., 68Ga, 18F) with comparisons to reference standards (estimated GFR or serum creatinine). Two authors independently screened titles/abstracts, extracted data, and assessed bias using Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). Exclusions included animal studies, reviews, and non-English articles. Results: Eleven studies met inclusion criteria, with 68Ga-EDTA showing the highest validation against reference standards such as 51Cr-EDTA plasma clearance, demonstrating strong correlation. PET imaging offered superior spatial–temporal resolution, enabling accurate split renal function assessment and quantitative analysis of both filtration and perfusion. 68Ga-somatostatin analogues exhibited moderate correlations between renal SUV and estimated GFR, with post-PRRT uptake changes indicating early nephrotoxicity. Among novel tracers, 68Ga-FAPI showed a strong inverse SUV–GFR relationship, reflecting renal fibrosis and suggesting potential as a chronic kidney disease (CKD) biomarker but requires further clinical validation. Limitations across studies include small sample sizes, retrospective designs, and variability in reference standards. Conclusions: PET radiotracers, particularly 68Ga-EDTA, represent a significant advancement for non-invasive, quantitative GFR measurement with improved precision and renal anatomical detail compared to traditional methods. Future prospective, large-scale human studies with standardized protocols are needed to establish these PET tracers as routine clinical tools in nephrology. Integration of hybrid PET/MRI and novel tracer development may further enhance renal diagnostic capabilities. Full article
(This article belongs to the Special Issue Applications of PET/CT in Clinical Diagnostics)
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