Search Results (98)

Background: Large-scale data on the diagnostic performance of functional imaging in metastatic pheochromocytoma/paraganglioma (PPGL) are scarce. Objective: To analyze the diagnostic accuracy of functional imaging for the assessment of metastases during long-term follow-up (FU). Design: Retrospective cohort study, 1991–2025. Setting: Referral center. Outcomes: Sensitivity and specificity of ¹²³MIBG-, ¹⁸F-DOPA-, ⁶⁸GaDOTA-based and ¹⁸FDG PET/CT. Patients: Patients with metastatic PPGL and without PPGL, ≥1 functional imaging prior to first diagnosis and/or during FU and FU ≥ 3 months. Results: 59 ¹²³MIBG-, 101 ¹⁸F-DOPA-, 11 ¹⁸FDG- and 74 ⁶⁸GaDOTA-based PET/CT were performed in 57 patients with metastatic PPGL and 37 ¹²³MIBG-, 323 ¹⁸F-DOPA-, 259 ¹⁸FDG- and 641 ⁶⁸GaDOTA-based imaging in 527 patients without PPGL. FU was 11.6 ± 11.4 and 5.1 ± 4.7 years, respectively. Sensitivity for the detection of all metastases (total cohort) by patient-based analysis was comparable between ¹⁸F-DOPA (77%), both ⁶⁸GaDOTA-based tracers combined (67%) and ¹²³MIBG (72%); lesion-based analysis was better for ¹⁸F-DOPA (94%) than for ⁶⁸GaDOTA (85%) and ¹²³MIBG (67%). Specificity (patient- and lesion-based) of ¹⁸F-DOPA vs. ⁶⁸GaDOTA (96–99%) was comparable and better than ¹²³MIBG (73%) and ¹⁸FDG (75%). Conclusions: Sensitivity of ¹⁸F-DOPA was superior to ⁶⁸GaDOTA for the detection of all and bone metastases in the total cohort and in patients with PCC, that of ⁶⁸GaDOTA was better for bone metastases with PGL, specificity was comparable and for both was better than for ¹⁸FDG and ¹²³MIBG. Given the beneficial pharmaceutical properties and favorable diagnostic performance, ¹⁸F-DOPA may be a good alternative to ⁶⁸GaDOTA-based tracers for the functional imaging of metastatic PPGL. Full article

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

Primary bone tumors encompass a heterogeneous spectrum ranging from benign entities to highly aggressive sarcomas. This review aims to summarize the current role and future perspectives of nuclear medicine in the diagnosis, staging, and management of primary bone tumors. Accurate diagnosis and staging are critical yet challenging due to histologic heterogeneity and overlapping imaging features. While radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) remain essential, nuclear medicine provides a complementary functional perspective by assessing bone turnover, vascularity, and glucose metabolism. Bone scintigraphy is highly sensitive for skeletal lesions and useful for detecting skip lesions or multifocal disease, although its specificity is limited. Hybrid single-photon emission computed tomography (SPECT)/CT enhances diagnostic confidence through precise anatomic localization and quantitation. [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET)/CT, by directly visualizing tumor metabolism, has become a cornerstone in osteosarcoma and Ewing sarcoma management, demonstrating superiority over bone scintigraphy for detecting skeletal metastases. In chondrosarcoma, [¹⁸F]FDG uptake correlates with histologic grade, although overlap with benign cartilage tumors complicates interpretation. Future directions include the integration of quantitative SPECT, artificial intelligence, and novel tracers such as [¹⁸F]sodium fluoride and [⁶⁸Ga]Ga-fibroblast activation protein inhibitor (FAPI). Collectively, nuclear medicine imaging is becoming a key element in musculoskeletal oncology, offering unique biological insights that complement anatomic imaging and contribute to improved patient management. Full article

Background: While prostate-specific membrane antigen (PSMA)-targeted imaging has revolutionized metastatic detection, unspecific bone uptake (UBU)—particularly in the ribs—is a common but diagnostically challenging finding in prostate cancer (PCa) patients. This review aims to synthesize current evidence on PSMA-avid rib lesions in PCa and to propose a structured approach for differentiating true metastases from benign mimics. Methods: A comprehensive literature search across PubMed, EMBASE, Scopus, and Web of Science identified relevant studies on PSMA imaging interpretation, tracer-specific patterns, rib lesion morphology, and clinical correlates. Data on uptake intensity, CT features, lesion number, location, tracer type, patient-specific risk factors, and follow-up behavior were extracted and analyzed. Results: Most solitary rib lesions are benign, particularly in low-risk patients or when located in the anterior/lateral arcs. Metastatic lesions are more likely to present as multiple foci, show cortical destruction on CT, exhibit high uptake intensity, and occur in patients with elevated PSA, high Gleason score, or ongoing androgen deprivation. ¹⁸F-PSMA-1007 is especially prone to UBU in the ribs compared to ⁶⁸Ga-PSMA-11. Based on these variables, we propose a clinical decision tree to guide interpretation of PSMA-avid rib lesions. Conclusions: Accurate interpretation of rib lesions on PSMA PET/CT requires a multimodal, context-sensitive approach. Our diagnostic decision tree guides precise differentiation of benign versus metastatic rib lesions, enhancing staging accuracy and clinical decision-making. Biomarker-guided therapies offer potential for personalized treatment, though rib-specific validation remains a critical need. Full article

Osteoarthritis involves complex interactions between articular joint tissues and the immune system, which is implicated in molecular trafficking via barrier-function modulating cytokines. The current study aims to test effects of an acute spike in TNF-α or TGF-β on vascular barrier function at multiple length scales, from the heart to tissue compartments of the knee, and cellular inhabitants of those respective compartments, in a spontaneous guinea pig model of osteoarthritis. First we quantified the intensity of a fluorescent-tagged 70 kDa tracer, similar in size to albumin, the most prevalent transporter protein in the blood, in tissue compartments of bone (periosteum, marrow space, compact bone, and epiphyseal bone) and cartilage (superficial cartilage, calcified cartilage, and the interface between, i.e., the epiphyseal line), as well as at sites of tendon attachment to bone (entheses). We then examined tracer presence and intensity in the respective pericellular and extracellular matrix zones of bone and cartilage. Acute exposure to TGF-β reduced barrier function (increased permeability) at nearest vascular interfaces in four of eight tissue compartments studied, compared to TNF-α where one of eight tissue compartments showed significant diminishment in barrier function. The increase in permeability associated with reduced barrier function was observed at both tissue compartment and cellular length scales. The observation of pericellular transport of the albumin-sized molecules to osteocytes contrasts with previous observations of barrier function in healthy, untreated animals and is indicative of increased molecular transport in pericellular regions of musculoskeletal tissues in cytokine-treated animals. Understanding age- and disease-related changes in molecular transport within musculoskeletal structures, such as the knee joint, is crucial for elucidating the etiology and pathogenesis of osteoarthritis. Full article

Background/Objectives: The diagnosis of osteomyelitis is typically based on clinical suspI icion supported by imaging and lab findings. Various nuclear medicine imaging, including bone SPECT/CT, is emerging as an effective tool to guide the diagnosis of osteomyelitis. This study investigates whether the preoperative ^99mTc DPD bone SPECT/CT uptake \ratio correlates with intraoperative tissue culture positivity in patients with suspected lower extremity osteomyelitis. Methods: We retrospectively reviewed 46 patients who underwent surgery for suspected osteomyelitis of the lower extremity between February 2020 and May 2025. Bone SPECT/CT was performed using ^99mTc DPD, and uptake values were measured using Syngo.via software. Lesion-to-Background Ratio (LBR) was calculated by comparing uptake in the lesion with the contralateral bone. Intraoperative culture was conducted at the region with high uptake in SPECT/CT. Results: Among the 46 patients who underwent surgery, 28 had positive tissue cultures, and 18 were negative. The mean LBR was significantly higher in culture-positive cases (14.5 ± 4.5) than in culture-negative cases (6.8 ± 8.0, p = 0.0002) Inflammatory markers (WBC, ANC, ESR, CRP) and the antibiotic-free interval before surgery did not significantly differ between groups or correlate with LBR. ROC analysis identified an LBR threshold of 9.44, yielding a sensitivity of 71.4% and specificity of 88.9% for predicting positive cultures (AUC = 0.81). Conclusions: ^99mTc DPD bone SPECT/CT uptake ratio may serve as a useful tool for the preoperative assessment of suspected lower extremity osteomyelitis, providing a more reliable prediction of intraoperative microbial culture results compared to serum inflammatory markers or the duration of antibiotic-free intervals. High tracer uptake may also be observed in various other conditions and thus should be interpreted in a multidisciplinary context in conjunction with other modalities. Full article

Background: ¹⁸F-NaF and ^99mTc-MDP are widely used bone imaging tracers, but their comparative uptake in bone versus cartilage is unclear. This study aimed to directly compare these patterns in rats to guide musculoskeletal molecular imaging. Methods: Male Sprague-Dawley rats underwent in vivo and ex vivo radiotracer studies. Tracer uptake (%ID/g) was quantified in bone and cartilage at 30, 60, or 120 min post-injection (¹⁸F-NaF or ^99mTc-MDP), and across different ages. Additional rats received subcutaneous implants of viable or devitalized bone and cartilage; uptake was assessed using PET/CT, autoradiography, and histology. Results: ¹⁸F-NaF showed faster blood/background clearance and higher target-to-background ratios compared to ^99mTc-MDP, especially in weight-bearing joint cartilage. ¹⁸F-NaF uptake in cancellous bone significantly exceeded that of ^99mTc-MDP, whereas ^99mTc-MDP showed higher uptake in knee cartilage. Age-related analysis showed maximal knee cartilage accumulation in aged rats. Histological and cell inactivation studies confirmed that ¹⁸F-NaF uptake reflects both cellular activity and degree of calcification. Conclusions:¹⁸F-NaF demonstrates distinctive, quantifiable uptake in cartilage, dependent on both cellular activity and calcification, and exhibits favorable imaging characteristics versus ^99mTc-MDP for cartilage metabolism. These findings support ¹⁸F-NaF as a promising tool for early diagnosis and therapeutic monitoring of bone and joint disorders, and provide pathophysiological insight into the dynamics of the bone–cartilage interface. Full article

Background/Objectives: Transthyretin cardiac amyloidosis (ATTR-CA) is an infiltrative cardiomyopathy caused by transthyretin (TTR) amyloid deposition in the myocardium, increasingly recognized in patients with aortic stenosis (AS). This study aims to investigate the diagnostic challenges and therapeutic strategies for patients with both conditions, focusing on shared pathophysiological mechanisms and key diagnostic indicators. Methods: A multimodal diagnostic approach was applied, utilizing cardiac magnetic resonance (CMR) and bone scintigraphy with technetium-99m-labeled tracers to assess AS patients with suspected ATTR-CA. Clinical signs, such as disproportionate heart failure symptoms, conduction abnormalities, and low-flow, low-gradient AS, were evaluated. Electrocardiographic findings, including low-voltage QRS complexes and pseudo-infarction patterns, were also assessed. Treatment options, including transcatheter aortic valve replacement (TAVR) and emerging pharmacotherapies for ATTR-CA, were analyzed. Results: The study found that ATTR-CA is increasingly prevalent in AS patients, with shared mechanisms like oxidative stress and amyloid-induced tissue remodeling. Key diagnostic signs include disproportionate heart failure symptoms, conduction abnormalities, and specific electrocardiographic patterns. TAVR was effective in both isolated AS and AS with ATTR-CA, although patients with both conditions had a higher risk of heart failure hospitalization and persistent symptoms. Emerging pharmacotherapies, such as TTR stabilizers and gene-silencing agents, showed promise in slowing disease progression. Conclusions: A multimodal diagnostic approach is essential for the early detection of ATTR-CA in AS patients. Combining TAVR with emerging pharmacotherapies may improve long-term outcomes for this high-risk group, enhancing patient care in those with both conditions. Full article

The inducible enzyme cyclooxygenase-2 (COX-2) and the subsequent synthesis of eicosanoids initiated by this enzyme are important molecular players in bone healing. In this pilot study, the suitability of a novel selective COX-2 inhibitor bearing a nitric oxide (NO)-releasing moiety was investigated as a modulator of healing a critical-size bone defect in rats. A 5 mm femoral defect was randomly filled with no material (negative control, NC), a mixture of collagen and autologous bone fragments (positive control, PC), or polycaprolactone-co-lactide (PCL)-scaffolds coated with two types of artificial extracellular matrix (aECM; collagen/chondroitin sulfate (Col/CS) or collagen/polysulfated hyaluronic acid (Col/sHA3)). Bone healing was monitored by a dual-tracer ([¹⁸F]FDG/[¹⁸F]fluoride) approach using PET/CT imaging in vivo. In addition, ex vivo µCT imaging as well as histological and immunohistochemical studies were performed 16 weeks post-surgery. A significant higher uptake of [¹⁸F]FDG, a surrogate marker for inflammatory infiltrate, but not of [¹⁸F]fluoride, representing bone mineralization, was observed in the implanted PCL-scaffolds coated with either Col/CS or Col/sHA3. Molecular targeting of COX-2 with NO-coxib had no significant effect on tracer uptake in any of the groups. Histological and immunohistochemical staining showed no evidence of a positive or negative influence of NO-coxib treatment on bone healing. Full article

The prevalence of cardiac amyloidosis (CA), especially as a cause of heart failure, has significantly increased in recent years. Early detection and accurate assessment of the disease burden are crucial for initiating timely treatment and ensuring precise prognosis. CA primarily results from the infiltration of the myocardium by either immunoglobulin light chain fibrils (AL) or transthyretin fibrils (ATTR), leading to restrictive cardiomyopathy and eventual death if untreated. Over the past decade, advancements in diagnostic imaging and heightened clinical awareness have revealed a substantial presence of CA, particularly ATTR, among the elderly. These diagnostic improvements encompass echocardiography, cardiac computerized tomography scans, magnetic resonance imaging, and radionuclide scintigraphy with bone-avid tracers. Concurrently, significant progress has been made in therapeutic options, with new disease-modifying treatments now available that can dramatically alter the disease trajectory and improve survival rates when administered early. However, despite these advancements, there remains an urgent need for the early and accurate detection of CA to ensure that patients can fully benefit from these emerging therapies. Full article

Over the past decade, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has revolutionized prostate cancer (PCa) imaging, offering greater sensitivity and specificity compared to conventional imaging modalities such as CT, MRI, and bone scintigraphy. PSMA-PET is particularly valuable in staging newly diagnosed patients with intermediate- and high-risk disease, detecting biochemical recurrence, and evaluating metastatic cases. By utilizing radiotracers that accumulate specifically in PSMA-expressing cells, even small metastases can be detected, offering a detailed assessment of cancer extent and enabling more targeted diagnostic evaluations. Among the most utilized radiotracers, [⁶⁸Ga]- and [¹⁸F]-labeled PSMA tracers enable precise imaging even with low disease burden. This diagnostic precision also supports advanced therapeutic approaches, including metastasis-directed therapy for oligometastatic cases and systemic treatment options, such as radioligand therapy, which presents new treatment perspectives for metastatic, castration-resistant PCa. This review examines the evolution of PSMA-PET in the diagnostics and therapy of PCa while comparing the current recommendations from leading clinical guidelines. The integration of PSMA-PET into clinical practice has redefined the management of PCa, improving diagnostic accuracy and enabling personalized treatment strategies, while lacking prospective long-term outcome data. As PSMA-PET continues to expand in clinical application, this review highlights its significant advancements while critically addressing limitations to ensure balanced and evidence-based implementation in prostate cancer care. Full article

A highly invasive species, free-ranging Sus scrofa often negatively impact the ecosystem and are capable of spreading a number of impactful pathogens to domestic livestock. Measures taken to ameliorate these impacts and/or control population size are based on the delivery of oral baits containing bioactive chemicals or vaccines, e.g., classical swine fever vaccine. The efficacy of these methods depends on the rate at which inoculated baits are consumed by the pigs. Rhodamine B, tetracycline, and iophenoxic acid are commonly used to quantitate bait uptake in free-ranging pig population studies. All three are effective in this application but differ in fundamental characteristics. When used as a tracer, the effective dose of rhodamine B was established at 15 mg/kg to ensure a 12-week window of detection based on evaluation of hair samples using fluorescent microscopy. Tetracyclines are likewise effective tracers in free-ranging pigs, but the process of detection is highly invasive, i.e., requires euthanasia, and extraction of bone or teeth, followed by examination by fluorescence microscopy. Iophenoxic acid and its derivatives also highly suitable tracers and may be detected in serum for ≥9 months after exposure. Notably tracers used in free-ranging pigs are not suitable for behavioral studies in farm-raised pigs either because the detection method is highly invasive (tetracyclines) or because they are unapproved for use in meat destined for human consumption. Full article

Background: Numerous PSMA-based tracers are used for diagnostic prostate cancer imaging, but comprehensive comparisons between multiple ligands are lacking. This study aimed to compare physiological skeletal uptake and tracer uptake in commonly recommended PSMA reference regions across three different PSMA ligands in prostate cancer patients. Methods: A total of 281 prostate cancer patients were included. Using PET and SPECT imaging, target volumes of interest were defined via a semiautomatic method, and standardized uptake values (SUV) were calculated for the skeletal system and reference regions (liver, spleen, parotid gland, and blood pool). Results: Significant differences in SUV uptake were observed, with [¹⁸F]F-PSMA-1007 showing higher SUV values in the skeletal system. The parotid gland displayed the highest variability in uptake, while the blood pool and liver exhibited more homogeneous uptake across patients. Conclusions: While radioligands behave similarly in bone regions, there are notable differences in SUV patterns, particularly for PSMA-1007, which showed higher bone uptake. Parotid gland uptake variability suggests a reconsideration of its suitability as a reference region, while the liver, spleen, and blood pool showed more consistent uptake. During comparison, the technetium-labeled SPECT ligand proved as similarly effective as the two PET ligands for diagnostic imaging. Full article

Background: Focal unspecific bone uptake (UBU) is common in [¹⁸F]PSMA-1007 PET/CT, yet its clinical significance remains unclear, causing uncertainty in treatment decisions. Material and Methods: We retrospectively analyzed 99 prostate cancer patients (age 69 ± 7) who underwent [¹⁸F]PSMA-1007 PET/CT scans (3 MBq/kg; uptake time 70 ± 14 min) for staging and follow-up (after 13.0 ± 7.2 months). Semiquantitative assessment using the miPSMA score, analogous to the PROMISE criteria, evaluated the prevalence of UBU and bone metastases. Results: In the initial PET/CT scan, 56 patients had 230 lesions classified as UBU. A total of 19 patients were found to have bone metastases and UBU, while 24 patients had no focal bone uptake. UBU distribution was as follows: ribs (50%), spine (30%), pelvis (15%), and other sites (5%). There were no significant differences in age, Gleason score, injected tracer dose, uptake time, SUV_peak of UBU, or SUV_mean in the spleen and parotid gland between patients with and without UBU. Follow-up showed stable miPSMA-score and CT appearance in 44/56 patients with UBU (79%), minor changes in 5/56 patients (8%), and new bone metastases in 7/56 patients (12%). Patient-specific analysis indicated at least one bone metastasis initially classified as UBU in 3/56 patients (5%) and new bone metastases in 4/56 patients (7%). In total, 4 of the 24 patients (17%) without initial focal uptake developed osseous metastases at follow-up. Conclusions: No significant differences were found between patients with or without UBU. Only a small portion of UBU (2%) evolved into metastases, a lower rate than the development of new osseous metastases, which appears to be independent of UBU. Full article

In mammals, nitric oxide (NO) is generated either by the nitric oxide synthase (NOS) enzymes from arginine or by the reduction of nitrate to nitrite by tissue xanthine oxidoreductase (XOR) and the microbiome and further reducing nitrite to NO by XOR or several heme proteins. Previously, we reported that skeletal muscle acts as a large nitrate reservoir in mammals, and this nitrate reservoir is systemically, as well as locally, used to generate nitrite and NO. Here, we report identifying two additional nitrate storage organs—bone and skin. We used bolus of ingested ¹⁵N-labeled nitrate to trace its short-term fluxes and distribution among organs. At baseline conditions, the nitrate concentration in femur bone samples was 96 ± 63 nmol/g, scalp skin 56 ± 22 nmol/g, with gluteus muscle at 57 ± 39 nmol/g. In comparison, plasma and liver contained 34 ± 19 nmol/g and 15 ± 5 nmol/g of nitrate, respectively. Three hours after ¹⁵N-nitrate ingestion, its concentration significantly increased in all organs, exceeding the baseline levels in plasma, skin, bone, skeletal muscle, and in liver 5-, 2.4-, 2.4-, 2.1-, and 2-fold, respectively. As expected, nitrate reduction into nitrite was highest in liver but also substantial in skin and skeletal muscle, followed by the distribution of ¹⁵N-labeled nitrite. We believe that these results underline the major roles played by skeletal muscle, skin, and bone, the three largest organs in mammals, in maintaining NO homeostasis, especially via the nitrate–nitrite–NO pathway. Full article