Search Results (92)

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

Here, we describe the case of a 43-year-old male patient with a metastatic parathyroid carcinoma who underwent dual-tracer whole-body positron emission tomography/computed tomography (PET/CT) with [¹⁸F]fluorocholine and fluorodeoxyglucose ([¹⁸F]FDG) for staging. [¹⁸F]FDG PET/CT detected multiple cervical and mediastinal lymph nodal lesions with increased tracer uptake, whereas [¹⁸F]fluorocholine PET/CT detected increased tracer uptake on cervical and mediastinal lymph nodal lesions and bone and lung lesions with a better evaluation of metastatic spread. Due to these imaging findings, the patient underwent systemic treatment with chemotherapy. This case demonstrates the added value of dual-tracer PET/CT in this rare metastatic tumor. Full article

Cardiac amyloidosis (CA) results mainly from the infiltration of the myocardium by either immunoglobulin light-chain fibrils (AL) or transthyretin fibrils (ATTR), causing restrictive cardiomyopathy and eventually death if untreated. AL derives from monoclonal immunoglobulin light chains produced by plasma cell clones in the bone marrow, while ATTR is the misfolded form of hepatically derived transthyretin (TTR) protein and can be hereditary (ATTRv) or wild-type (ATTRwt). Over the last decade, improvements in diagnostic imaging and better clinical awareness have unleashed a notable presence of CA in the community, especially ATTR in the elderly population. These multimodality imaging modalities include echocardiography, cardiac magnetic resonance, and radionuclide scintigraphy with bone-avid tracers. There has been remarkable progress in the therapeutic landscape as well, and there are disease-modifying therapies available now that can alter the course of the disease and improve survival if initiated at an early stage of the disease. There remains an unmet need for detecting this disease accurately and early so that these patients can benefit the most from newly emerging therapies. Full article

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[¹⁸F]fluoroethyl)-L-tryptophan (L-[¹⁸F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[¹⁸F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[¹⁸F]FETrp had a comparable tumor uptake with [¹⁸F]fluorodeoxyglucose (FDG). However, L-[¹⁸F]FETrp showed a significantly higher tumor-to-brain ratio than FDG (n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[¹⁸F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan–kynurenine pathway as a therapeutic target for treating NF1. Full article

The present report describes the history of a 58-year-old woman with a rapidly progressing neuroendocrine pancreatic tumor (initially G2) presenting with extensive liver, bone, and lymph node metastases. Previous treatments included chemotherapy, hemithyroidectomy for right lobe metastasis, Peptide Receptor Radionuclide Therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTATATE, Lanreotide, Everolimus, and liver embolization. Due to severe disease progression, after a liver biopsy revealing tumor grade G3, PRRT with the somatostatin receptor antagonist LM3 was initiated. [⁶⁸Ga]GaDOTA-LM3 PET/CT showed intense tracer uptake in the liver, pancreatic tumor, lymph nodes, and bone metastases. Three TANDEM-PRRT cycles using [¹⁷⁷Lu]LuDOTA-LM3 and [²²⁵Ac]AcDOTA-LM3, administered concurrently, resulted in significant improvement, notably in liver metastases, hepatomegaly reduction, the complete regression of bone and lymph node metastases, and primary tumor improvement. Partial remission was confirmed by positron emission tomography/computed tomography, chest–abdomen–pelvis contrast-enhanced computed tomography, and magnetic resonance of the abdomen, with marked clinical improvement in pain, energy levels, and quality of life, enabling full resumption of physical activity. Full article

Background: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is characterized by lymphoproliferation and increased risk of malignancy. FDG-PET/CT may represent a helpful diagnostic tool for differentiating these clinical features and correctly diagnosing inborn errors of immunity (IEI). Case report: We present the case of a female patient diagnosed with Hodgkin’s lymphoma at 19 years of age, although atypical imaging aspects emerged: baseline FDG-PET/CT revealed several hot lymph nodes with a symmetrical distribution, and increased tracer uptake in spleen, axial, and appendicular bone marrow. Imaging repeated after chemotherapy and autologous stem cell transplantation showed persistent increased FDG uptake at multiple supradiaphragmatic nodes and in bone marrow. After the diagnosis of APDS2 and rapamycin treatment, FDG-PET/CT confirmed complete metabolic normalization of all sites. Conclusions: In the IEI scenario, FDG-PET/CT plays an effective role in differentiating malignant proliferation and immune dysregulation phenotypes. Atypical patterns at FDG-PET/CT should be interpreted as a red flag for the need of an early immunological evaluation. Full article

Objectives: The purpose of this study was to investigate the imaging characteristics of medication-related osteonecrosis of the jaw (MRONJ) using [18F]fluoride positron emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) for preoperative assessment and to correlate them with microarchitectural and histomorphometric data with respect to clinical findings. Methods: Twelve patients (five female; mean age 75 ± 7.6 yr) with symptomatic MRONJ underwent both scans on the same day, and imaging findings were used to plan surgical interventions for seven patients. Bone tracer uptake was classified as high, medium, or low, and surgical samples were evaluated using Micro-CT and histomorphometric analysis. Results: CT showed medullary sclerosis in all patients, and MRI revealed gadolinium enhancement in four patients. PET imaging revealed remarkably elevated [18F]fluoride uptake and moderately increased [18F]FDG uptake in MRONJ compared to healthy jawbones, with both differences being statistically significant. [18F]fluoride uptake was associated with necrosis, bacteria, and inflammatory tissue. Micro-CT data did not show significant differences, but histomorphometric analysis revealed higher osteocyte and lacunae densities in the high [18F]fluoride uptake group, and more necrotic bone in the medium [18F]fluoride uptake group. Bacteria were observed in all areas. Conclusions: In summary, [18F]fluoride PET accurately identified MRONJ extent, revealing functional changes in jawbone remodeling not visible on CT. [18F]FDG PET showed differences in bone and soft tissue, though less pronounced. This method aids in evaluating disease activity and guiding treatment planning, requiring further research for optimal surgical approaches based on tracer uptake. Full article