Search Results (235)

Background/Objectives: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially improves staging, stratification, and therapy of cancer patients. This study explores a dual-tracer SPECT approach using [¹¹¹In]In-RM2 (targeting the gastrin-releasing peptide receptor, GRPR) and [^99mTc]Tc-PSMA-I&S (targeting the prostate-specific membrane antigen, PSMA) as a proof of concept. To mimic heterogeneous tumor lesions in the same individual, we aimed to establish a dual xenograft mouse model for preclinical evaluation. Methods: CHO-K1 cells underwent lentiviral transduction for human GRPR or human PSMA overexpression. Six-to-eight-week-old female immunodeficient mice (NOD SCID) were subsequently inoculated with transduced CHO-K1 cells in both flanks, enabling a dual xenograft with similar target density and growth of both xenografts. Respective dual-isotope imaging and γ-counting protocols were established. Target expression was analyzed ex vivo by Western blotting. Results: In vitro studies showed similar target-specific binding and internalization of [¹¹¹In]In-RM2 and [^99mTc]Tc-PSMA-I&S in transduced CHO-K1 cells compared to reference lines PC-3 and LNCaP. However, in vivo imaging showed negligible tumor uptake in xenografts of the transduced cell lines. Ex vivo analysis indicated a loss of the respective biomarkers in the xenografts. Conclusions: Although the technical feasibility of a dual-tracer SPECT imaging approach using ¹¹¹In and ^99mTc has been demonstrated, the potential of [^99mTc]Tc-PSMA-I&S and [¹¹¹In]In-RM2 in a dual-tracer cocktail to improve PCa diagnosis could not be verified. The animal model, and in particular the transduced cell lines developed exclusively for this project, proved to be unsuitable for this purpose. The in/ex vivo experiments indicated that results from an in vitro model may not necessarily be successfully transferred to an in vivo setting. To assess the potential of this dual-tracer concept to improve PCa diagnosis, optimized in vivo models are needed. Nevertheless, our strategies address key challenges in dual-tracer applications, aiming to optimize future SPECT imaging approaches. Full article

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

Background: Granulomatous and amyloidogenic cardiomyopathies are infiltrative conditions that can be fatal if left untreated. Among these, cardiac amyloidosis and cardiac sarcoidosis are significant but often underdiagnosed causes of heart failure, each serving as cardiac manifestations of broader systemic diseases. Advancements in imaging techniques and the emergence of novel therapies—particularly for cardiac amyloidosis—have brought these conditions into sharper focus for both clinicians and researchers. Methods: We conducted a comprehensive review of the literature by searching databases including PubMed and Scopus for studies published since 1990 regarding clinical features, diagnostic techniques, and treatment strategies for cardiac amyloidosis and cardiac sarcoidosis. Studies were selected based on relevance to imaging methods, including echocardiography, cardiac magnetic resonance imaging (CMR), positron emission tomography (PET), and technetium-labeled nuclear scintigraphy, as well as treatment modalities for both conditions. Results: Imaging techniques, particularly CMR, technetium-labeled nuclear scan, and PET, were found to be crucial for the early identification and differentiation of cardiac amyloidosis and cardiac sarcoidosis. Distinct late gadolinium enhancement patterns were observed in CMR along with morphological differences, aiding in diagnosis. Technetium-labeled nuclear scintigraphy can definitively distinguish between subtypes of cardiac amyloidosis in the absence of paraproteinemia. Early diagnosis has been shown to significantly improve patient outcomes. Early treatment can reduce morbidity in both cardiomyopathies. Conclusions: Multimodality imaging can help in the early detection of cardiac amyloidosis and cardiac sarcoidosis. Treatment strategies differ substantially: cardiac amyloidosis is primarily managed with disease-modifying therapies for the transthyretin subtype and chemotherapy/stem cell transplant for the AL subtype, while cardiac sarcoidosis is treated with corticosteroids and immunosuppressive drugs to reduce inflammation. Early and accurate diagnosis through advanced imaging techniques is critical to improving outcomes for patients with these conditions. Full article

Amphiphilic diblock copolymers comprising polyethylene glycol (PEG) and 1-vinyl imidazole (VIM) were synthesized using reversible addition–fragmentation chain transfer (RAFT) polymerization. The study focused on the synthesis of well-defined nanostructures with tunable composition and their functional modification for biomedical applications. The successful polymerization of PEG-b-PVIM diblock copolymers was confirmed via ¹H NMR spectroscopy, and their molecular weights were analyzed using gel permeation chromatography (GPC). The copolymers exhibited pH-responsive behavior, with effective pK values of approximately 4.2. To facilitate radiolabeling and in vivo tracking, a post-polymerization modification enabled the conjugation of a 1,4,7-Triazacyclononane-1,4,7-triacetic acid (NOTA) chelator via aminolysis. The final conjugates were purified and characterized, confirming successful functionalization. These findings highlight the potential of PEG_x-b-PVIM_y diblock copolymers for biomedical applications. Full article

Background/Objectives: Neurotensin receptors (NTSRs), members of the G protein-coupled receptor (GPCR) family, have been found to be overexpressed in several types of human cancers, including breast, colon, lung, liver, prostate, and pancreatic cancer. In particular, NTSR1 is overexpressed in at least 75% of pancreatic ductal adenocarcinomas. The aim of the present study was the development and evaluation of new ^99mTc-labeled nonpeptide NTSR1-antagonists for SPECT imaging of NTSR-positive tumors. Methods: Multistep syntheses of NTSR1 antagonist derivatives were performed following our previously described procedure. Two different chelating strategies were applied for ^99mTc radiolabeling to provide the [^99mTc]Tc-HYNIC complex [^99mTc]1 and the [^99mTc]Tc-tricarbonyl complex [^99mTc]2. Receptor binding assays were performed using hNTSR1-expressing CHO cells. Radiochemical yields (RCYs) were determined by radio-HPLC. For [^99mTc]1 and [^99mTc]2, log D_7.4, plasma protein binding, stability in human plasma and serum, and cellular uptake in HT-29 cells were determined. Biodistribution studies and small animal SPECT studies were performed in HT-29 tumor-bearing nude mice. Results: The radiosynthesis of [^99mTc]1 (log D_7.4 = −0.27) and [^99mTc]2 (log D_7.4 = 1.00) was successfully performed with RCYs of 94–96% (decay-corrected). Both radioligands were stable in human serum and plasma, showed plasma protein binding of 72% ([^99mTc]1) and 82% ([^99mTc]2), and exhibited high and specific uptake in HT-29 cells. Biodistribution studies in HT-29 tumor-bearing mice showed a higher tumor accumulation of [^99mTc]1 compared to [^99mTc]2 (8.8 ± 3.4 %ID/g vs. 2.7 ± 0.2 %ID/g at 2 h p.i.). [^99mTc]2 showed exceptionally high intestinal accumulation (49 ± 22 %ID/g at 1 h p.i.) and was therefore considered unfavorable. In the SPECT/CT imaging of HT-29 tumor xenografts, [^99mTc]1 showed a higher NTSR1-specific tumor uptake than [^99mTc]2 at all time points after tracer injection, with 12 ± 2.8 %ID/g for [^99mTc]1 vs. 3.1 ± 1.1 %ID/g for [^99mTc]2 at 4 h p.i. and adequate tumor-to-background ratios. Conclusions: In particular, the [^99mTc]Tc-HYNIC ligand ([^99mTc]1) showed promising preclinical results, being a potential candidate for SPECT imaging and, therefore, appropriate for translation into the clinic. Full article

Background/Objectives: Lipoxins, particularly Lipoxin A4 (LXA4), are endogenous lipid mediators with potent anti-inflammatory and pro-resolving properties, making them promising candidates for the treatment of inflammatory and neurodegenerative disorders. However, their therapeutic application is limited by poor stability and bioavailability. This study aimed to develop and characterize nanomicelles encapsulating LXA4 (nano-lipoxin A4) to improve its pharmacological efficacy against Alzheimer’s disease (AD), a neurodegenerative condition marked by chronic inflammation and beta-amyloid (Aβ) accumulation. Methods: Nano-lipoxin A4 was synthesized using Pluronic F-127 as a carrier and characterized in terms of morphology, physicochemical stability, and in vitro activity against Aβ fibrils. Dissociation of Aβ fibrils was assessed via Thioflavin-T fluorescence assays and transmission electron microscopy. In vivo biodistribution and pharmacokinetic profiles were evaluated using technetium-99m-labeled nano-lipoxin A4 in rodent models. Hepatic biochemical parameters were also measured to assess potential systemic effects. Results: In vitro studies demonstrated that nano-lipoxin A4 effectively dissociated Aβ fibrils at concentrations of 50 nM and 112 nM. Electron microscopy confirmed the disruption of fibrillar structures. In vivo imaging revealed predominant accumulation in the liver and spleen, consistent with reticuloendothelial system uptake. Pharmacokinetic analysis showed a prolonged half-life (63.95 h) and low clearance rate (0.001509 L/h), indicating sustained systemic presence. Biochemical assays revealed elevated liver enzyme levels, suggestive of increased hepatic metabolism or potential hepatotoxicity. Conclusions: Nano-lipoxin A4 exhibits significant therapeutic potential for Alzheimer’s disease through effective modulation of Aβ pathology and favorable pharmacokinetic characteristics. However, the elevation in liver enzymes necessitates further investigation into systemic safety to support clinical translation. Full article

Background: While sentinel lymph node (SLN) biopsy has been integrated into international guidelines for endometrial cancer, a standardized technique is still lacking. This study addresses whether the concurrent use of two tracers, technetium-99 (Tc) and indocyanine green (ICG), administered intracervically through distinct techniques, enhances the performance of SLN biopsies. As the blue dye is used routinely by some centers, it can be used alone; however, our analysis focused on only Tc and ICG (as is used in the majority of centers). Methods: A prospective multicentric observational study was designed to evaluate the unilateral detection rate, bilateral detection rates, sensitivity, and consistency of SLNs when using both tracers simultaneously in patients with early-stage endometrial cancer. Results: Our findings demonstrated that the simultaneous use of ICG and Tc significantly outperformed the use of either tracer alone. Unilateral detection rates were 69.2% for Tc, 84.9% for ICG, and 88.4% for both. Bilateral detection rates were 57.0% for Tc, 77.9% for ICG, and 83.6% for both. Additionally, the incidence of “empty pockets” was low with both tracers, at 2.7%. Notably, the concurrent application of both tracers identified instances where the Tc-labeled sentinel node differed from the ICG-labeled sentinel node. Conclusions: The combined use of Tc and ICG in SLN biopsy for early-stage endometrial cancer significantly enhances detection rates and reduces the occurrence of “empty pockets”, potentially decreasing the need for site-specific lymphadenectomy. 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

Background and Objectives: To summarize the evidence on in vivo uterine pelvic lymphatic drainage. Materials and Methods: A literature search was performed in multiple electronic databases from inception to December 2024. We included all the studies that compared two different uterine injection sites in the mapping of pelvic sentinel lymph nodes by injecting two different tracers into two distinct injection sites. The primary outcomes included the concordance and discordance rates in the mapped pelvic sentinel lymph nodes between the pairs of injection sites. The secondary outcomes were the detection rates per injection site and tracer. Four reviewers independently reviewed the records for inclusion, assessed the risk of bias, and extracted the data. Pooled concordance, discordance, and detection rates with 95% confidence intervals (CIs) were estimated using the random effects model. Heterogeneity was quantified using the I² tests. Results: Out of 2512 records, we included 4 studies (172 patients and 344 hemipelves). Three studies injected the cervix with the technetium-99m and the uterine corpus with methylene blue; one study injected the cervix with indocyanine green and the utero-ovarian ligament with methylene blue. Both tracers/injection sites successfully identified a sentinel lymph node in 132 hemipelves (132/344; 38.4%), identifying the same sentinel lymph node in 116 cases (116/132; 87.9%). The pooled concordance rate per hemipelvis was 91.8% (95% CI 0.665–1.000; I² = 92%; chi² p-value < 0.01). Two different sentinel lymph nodes were identified in the remaining 16 hemipelves, with a pooled hemipelvis discordance rate of 8.2% (95% CI 0.000–0.335; I² = 92%; chi² p-value < 0.01). The cervix and technetium-99m were the injection site and tracer with the highest pooled detection rate. Conclusions: Different uterine injection sites appear to share a common pelvic lymphatic pathway and sentinel lymph node in most cases, consistent with the current practice in endometrial cancer. Future research will confirm whether cervical injections might be proposed for pelvic sentinel lymph node mapping in all gynecological cancers. Full article

Background/Objectives: Studies have indicated that forgoing lung shunt fraction measurement in select patients undergoing Yttrium 90 (Y90) transarterial radioembolization (TARE) may be safe without sacrificing efficacy. This study evaluated the safety and efficacy of a streamlined treatment in patients with small hepatocellular carcinoma (HCC) receiving resin-based TARE. Methods: Patients who received single-session Y90 TARE between September 2023 and May 2024 were retrospectively evaluated. Treatment response was evaluated at the 3-month follow-up using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Adverse events (AEs) ≥ Grade 3 were recorded post-procedurally at 3 months. The time from the interventional radiology clinic visit to the procedure date was compared to patients receiving the conventional TARE treatment. Results: Ten consecutive patients were treated with 12 treatments. Each treatment targeted an isolated lesion with median size of 2.5 cm (IQR: 2.1, 2.9). Two patients received two treatments (one for treatment of a separate lesion and the other for the initial incomplete targeting of the tumor). The median delivered tumor dose was 377.7 Gy (IQR: 246.5, 570.1). No patients developed ≥ Grade 3 AEs post-TARE. Complete response was achieved in 11/12 patients (92%). The conventional cohort consisted of 60 patients, all OPTN T2 treated with radiation segmentectomy with glass microspheres. Patients undergoing SSMT had a median time from clinic visit to treatment of 26.5 days (IQR: 15.3, 39) vs. 61 days (IQR: 48, 88.8) in the conventional TARE group (p < 0.001). Conclusions: Streamlined single-session resin-based Y90-TARE in patients with OPTN T2 stage HCC is feasible, efficacious, safe, and associated with reduced time to treatment. Full article

Tungsten oxide (WO₃) is a high-density material with exceptional radiation attenuation properties, making it a strong candidate for advanced shielding applications. This study explores the structural, mechanical, and shielding performance of WO₃-reinforced polyisoprene composites. Morphological analysis reveals a plate-like structure, indicating robust interfacial interactions that enhance mechanical integrity and thermal stability. X-ray diffraction confirms the crystalline nature of WO₃, while Fourier transform infrared spectroscopy detects distinct W–O bond absorption bands, validating uniform dispersion. Computational analysis using XCOM demonstrates remarkable improvements in attenuation properties, particularly at intermediate- and high-photon energies. While PbO₂ outperforms at lower energies due to the photoelectric effect, Phy-X/PSD analysis confirms that composites with ≥75% WO₃ offer strong shielding capabilities. Variations in effective atomic number, linear attenuation coefficient, and mass attenuation coefficient establish WO₃-reinforced NR as a compelling lead-free alternative, especially for Tc-99m applications. Experimental findings further reveal that increasing WO₃ content significantly reduces Tc-99m gamma radiation dose equivalents Hp(0.07), Hp(3), and Hp(10), emphasizing the potential of WO₃-reinforced composites for next-generation radiation shielding solutions. Full article

Background/Objectives: The high success rate of minimally invasive parathyroidectomy (MIP) is dependent upon the correct preoperative localization of the solitary parathyroid adenoma (SPA). Various studies have focused on comparisons of radiologist-performed ultrasound (RUS) and surgeon-performed ultrasound (SUS) to increase the sensitivity rate of US. However, the efficiency of radiologist- and surgeon-performed ultrasound (RSUS) before MIP has not frequently been reported. We aimed to evaluate the efficiency of RSUS in clinical practice. Methods: In total, 122 patients (107 females, 15 males, mean age: 47.62 ± 15.75 years) with SPA were enrolled in our study design. The patients underwent preoperative ultrasonography (US) and technetium-99-sestamibi scintigraphy. Patient data including demographic characteristics, levels of biochemical parameters (parathyroid hormone (PTH), total serum calcium and phosphorus levels), operation time, and length of hospital stay were recorded. Results: MIP was performed with success under local anesthesia following the accurate localization of the adenomas by RSUS. The mean operation time was 20.00 ± 3.87 min. The mean preoperative serum PTH, calcium, and phosphorus levels were 525.69 ± 1050.92 pg/mL, 11.38 ± 1.22 mg/dL, and 2.53 ± 0.60 mg/dL, respectively. The decline in the perioperative PTH and calcium levels reflecting a cure was observed on the first postoperative day. Postoperative sixth month evaluations of the PTH and calcium levels confirmed the significant decrease, reflecting the therapeutic cure. Since no complications occurred, the hospital discharge process was carried out on the same day. Conclusions: RSUS is a beneficial adjunctive tool to facilitate MIP, and it achieved satisfactory therapeutic success in all the patients. Full article

Background: Pulmonary circulation typically shows flow divided between the right and left lungs, with a marked predominance of the right lung. Pneumonectomy reduces pulmonary circulation by ~50%, irreversibly changing the pulmonary perfusion characteristics. Here we assessed pulmonary flow after pneumonectomy and investigated how selected factors influenced pulmonary perfusion in this patient group. Methods: This study included 31 patients who underwent pneumonectomy complicated by postpneumonectomy pleural empyema, which was successfully treated, with long-term survival. Testing was conducted at a median of 1100 days after pneumonectomy, after flow stabilization. The control group comprised 31 subjects without pulmonary pathology. Pulmonary flow was assessed by scintigraphy using Technetium (99m-Tc). Results: The average single lung perfusion after pneumonectomy corresponded to the total perfusion in both lungs in the control group without statistic difference between comparable parameters (upper field, 21.35 vs. 22.129, p = 0.4; middle field, 47.15 vs. 49.62, p = 0.099; lower field 30.71 vs. 28.29, p = 0.14). Compared to those with left-sided pneumonectomy, patients with right-sided pneumonectomy exhibited increased upper field perfusion (22.61 vs. 19.82, p = 0.049) and decreased perfusion in the lower field (30.81 vs. 26.22, p = 0.049) and the combined middle and lower field (79.63 vs. 76.49, p = 0.046). Pulmonary flow was not significantly related to age, side of surgery, or empyema duration. Conclusions: Flow rate in the remaining lung after pneumonectomy corresponded to the total flow in both lungs in healthy controls. The perfusion ratio differed after right-sided versus left-sided pneumonectomy, which may be related to the initial anatomical differences of the right and left lung. Full article

Background/Objectives: Cardiac amyloidosis (CA) is associated with amyloid infiltration of the extra-cardiac tissue, which may occur in the early stages of the disease. This study evaluates the diagnostic utility of thoracic fat pad biopsy obtained during a pacemaker or ICD implantation as an alternative to the standard diagnostic criteria for systemic amyloidosis. Methods: This exploratory, retrospective study included 27 patients with suspected or diagnosed CA who underwent pacemaker or defibrillator therapy. Results: Of these, 16 patients were confirmed to have CA (15 with technetium-labeled bisphosphonate bone scintigraphy and 1 with protein electrophoresis and echocardiographic findings) while 11 were confirmed to be CA-negative. The thoracic fat pad biopsy demonstrated a specificity of 100% but a sensitivity of only 31%. Among patients with transthyretin (ATTR)-CA, the sensitivity remained similarly low, at 27%. These results are consistent with prior findings on abdominal fat pad biopsy in ATTR-CA, highlighting the limited diagnostic yield of this method. Conclusions: Thoracic fat pad biopsy cannot be recommended as a standard diagnostic tool for CA, particularly in ATTR-CA, due to its poor sensitivity. However, in AL (amyloid light-chain) amyloidosis, this minimally invasive procedure may aid diagnosis without additional invasive interventions. Full article

Background: The development of nanostructured materials for cancer therapy has garnered significant interest due to their unique physicochemical properties, including enhanced surface area and tunable electronic structures, which can facilitate targeted drug delivery and oxidative stress modulation. This study investigates the anticancer potential of monoclinic silver dimolybdate nanorods (m-Ag₂Mo₂O₇) against aggressive breast (MDA-MB-231) and prostate (PC-3) cancer cells and explores their in vivo pharmacokinetic behavior. Methods: m-Ag₂Mo₂O₇ nanorods were synthesized via a hydrothermal method and characterized using XRD, SEM, Raman, and FTIR spectroscopy. In vitro cytotoxicity was evaluated using MTT assays on MDA-MB-231 and PC-3 cell lines across concentrations ranging from 1.56 to 100 µg/mL. In vivo biodistribution and radiopharmacokinetics were assessed using technetium-99m-labeled nanorods in male Swiss rats, with gamma counting employed for tissue uptake analysis and pharmacokinetic parameter determination. Results: m-Ag₂Mo₂O₇ nanorods exhibited a modest cytotoxic effect on MDA-MB-231 cells, with 50 µg/mL reducing cell viability by 23.5% (p < 0.05), while no significant cytotoxicity was observed in PC-3 cells. In vivo studies revealed predominant accumulation in the stomach, liver, spleen, and bladder, indicating reticuloendothelial system uptake and renal clearance. Pharmacokinetic analysis showed a rapid systemic clearance (half-life ~6.76 h) and a low volume of distribution (0.0786 L), suggesting primary retention in circulation with minimal off-target diffusion. Conclusions: While m-Ag₂Mo₂O₇ nanorods display limited standalone cytotoxicity, their ability to induce oxidative stress and favorable pharmacokinetic profile support their potential as adjuvant agents in cancer therapy, particularly for chemoresistant breast cancers. Further studies are warranted to elucidate their molecular mechanisms, optimize combinatorial treatment strategies, and assess long-term safety in preclinical models. Full article