Search Results (23)

Background/Objectives: Cervical cancer primarily disseminates through the lymphatic system, with the metastatic involvement of pelvic and para-aortic lymph nodes significantly impacting prognosis and treatment decisions. Sentinel lymph node (SLN) mapping is critical in guiding surgical management. However, resource-limited settings often lack advanced detection tools like indocyanine green (ICG). This study evaluated the feasibility and effectiveness of SLN biopsy using alternative techniques in a high-risk population with a high prevalence of large tumours. Methods: This prospective, observational study included 42 patients with FIGO 2018 stage IA1–IIA1 cervical cancer treated between November 2019 and April 2024. SLN mapping was performed using methylene blue alone or combined with a technetium-99m radiotracer. Detection rates, sensitivity, and false-negative rates were analysed. Additional endpoints included tracer technique comparisons, SLN localization patterns, and factors influencing detection success. Results: SLNs were identified in 78.6% of cases, with bilateral detection in 57.1%. The combined technique yielded higher detection rates (93.3% overall, 80% bilateral) compared to methylene blue alone (70.4% overall, 40.7% bilateral, p < 0.05). The sensitivity and negative predictive values were 70% and 93.87%, respectively. Larger tumours (>4 cm), deep stromal invasion, and prior conization negatively impacted detection rates. False-negative SLNs were associated with larger tumours and positive lymphovascular space invasion. Conclusions: SLN biopsy is feasible in resource-limited settings, with improved detection rates using combined tracer techniques. However, sensitivity remains suboptimal due to a steep learning curve and challenges in high-risk patients. Until a high detection accuracy is achieved, SLN mapping should complement, rather than replace, pelvic lymphadenectomy in high-risk cases. Full article

Radionuclide bone scintigraphy is the cornerstone of an imaging-based algorithm for accurate non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). In patients with heart failure and suggestive echocardiographic and/or cardiac magnetic resonance imaging findings, the positive predictive value of Perugini grade 2 or 3 myocardial uptake on a radionuclide bone scan approaches 100% for the diagnosis of ATTR-CA as long as there is no biochemical evidence of a clonal dyscrasia. The technetium-labelled tracers that are currently validated for non-invasive diagnosis of ATTR-CA include pyrophosphate (^99mTc-PYP); hydroxymethylene diphosphonate (^99mTc-HMDP); and 3,3-diphosphono-1,2-propanodicarboxylate (^99mTc-DPD). Although nuclear scintigraphy has transformed the contemporary diagnostic approach to ATTR-CA, a number of grey areas remains, including the mechanism for binding tracers to the infiltrated heart, differences in the kinetics and distribution of these radiotracers, differences in protocols of image acquisition worldwide, the clinical significance of extra-cardiac uptake, and the use of this technique for prognostic stratification, monitoring disease progression and assessing the response to disease-modifying treatments. This review will deal with the most relevant unmet needs and clinical questions concerning scintigraphy with bone tracers in ATTR-CA, providing expert opinions on possible future developments in the clinical application of these radiotracers in order to offer practical information for the interpretation of nuclear images by physicians involved in the care of patients with this ATTR-CA. Full article

When developing novel radiopharmaceuticals, a linker moiety between the chelator and targeting vector can have a crucial influence on adjusting the affinity of the tracer and its biodistribution in organisms. To develop novel ^99mTc-labelled hypoxia imaging radiotracers, in this study, five isocyanide-containing 2-nitroimidazole derivatives with different linkers (L1, L2, L3, L4 and L5) were synthesised and radiolabelled with technetium-99m to obtain five stable ^99mTc-complexes ([^99mTc]Tc-L1, [^99mTc]Tc-L2, [^99mTc]Tc-L3, [^99mTc]Tc-L4 and [^99mTc]Tc-L5). Corresponding rhenium analogues of [^99mTc]Tc-L1 were synthesised and suggested the structures of these ^99mTc-complexes would be a monovalent cation with a technetium (I) core surrounded by six ligands. [^99mTc]Tc-L1 is hydrophilic, while the lipophilicities of [^99mTc]Tc-L2, [^99mTc]Tc-L3, [^99mTc]Tc-L4 and [^99mTc]Tc-L5 are close. In vitro cell experiments showed that all five novel ^99mTc-complexes had higher uptake in hypoxic cells compared with aerobic cells, which indicates the complexes have good hypoxia selectivity. The biodistribution of the five ^99mTc-complexes in S180 tumour-bearing mice showed that they all had certain uptake in the tumours. Among them, [^99mTc]Tc-L1 had the highest tumour-to-muscle (4.68 ± 0.44) and tumour-to-blood (3.81 ± 0.46) ratios. The introduction of polyethylene glycol (PEG) chains effectively reduced the lipophilicity and decreased uptake by the liver, intestine and blood but also increased clearance from the tumours. In vivo metabolic studies showed [^99mTc]Tc-L1 kept intact and remained stable in tumour, blood and urine at 2 h post-injection. The results of SPECT imaging showed that [^99mTc]Tc-L1 had significant tumour uptake at 2 h post-injection, but there was still high uptake in abdominal organs such as the liver and kidney, suggesting that this complex needs to be further optimised before being used for tumour hypoxia imaging. Full article

Non-invasive brain stimulation (NIBS) interventions are promising for the treatment of psychiatric disorders. Notwithstanding, the NIBS mechanisms of action over the dorsolateral prefrontal cortex (DLPFC), a hub that modulates affective and cognitive processes, have not been completely mapped. We aimed to investigate regional cerebral blood flow (rCBF) changes over the DLPFC and the subgenual anterior cingulate cortex (sgACC) of different NIBS protocols using Single-Photon Emission Computed Tomography (SPECT). A factorial, within-subjects, double-blinded study was performed. Twenty-three healthy subjects randomly underwent four sessions of NIBS applied once a week: transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), combined tDCS + iTBS and placebo. The radiotracer 99m-Technetium-ethylene-cysteine-dimer was injected intravenously during the NIBS session, and SPECT neuroimages were acquired after the session. Results revealed that the combination of tDCS + iTBS increased right sgACC rCBF. Cathodal and anodal tDCS increased and decreased DLPFC rCBF, respectively, while iTBS showed no significant changes compared to the placebo. Our findings suggest that the combined protocol might optimize the activity in the right sgACC and encourage future trials with neuropsychiatric populations. Moreover, mechanistic studies to investigate the effects of tDCS and iTBS over the DLPFC are required. Full article

We hereby propose the use of stable, biocompatible, and uniformly sized polymeric micelles as high-radiotracer-payload carriers at region-of-interest with negligible background activity due to no or low offsite radiolysis. We modified glycol chitosan (GC) polymer with varying levels of palmitoylation (P) and quaternization (Q). Quaternary ammonium palmitoyl glycol chitosan (GCPQ) with a Q:P ratio of 9:35 (Q9P35GC) offers >99% biocompatibility at 10 mg mL⁻¹. Q9P35GC micelles exhibit >99% ^99mTechnetium (^99mTc) radiolabeling via the stannous chloride reduction method without heat. The ^99mTc-Q9P35GC micelles (65 ± 3 nm) exhibit >98% 6 h serum stability at 37 °C and 7 day of radiochemical stability at 25 °C. HepG2 cells show a higher uptake of FITC-Q9P35GC than Q13P15GC and Q20P15GC. The in vivo 24 h organ cumulated activity (MBq h) order follows: liver (234.4) > kidneys (60.95) > GIT (0.73) > spleen (88.84). The liver to organ ratio remains higher than 2.4, rendering a better contrast in the liver. The radiotracer uptake decreases significantly in fibrotic vs. normal liver, whereas a blocking study with excess Q9P35GC significantly decreases the radiotracer uptake in a healthy vs. fibrotic liver. FITC-Q9P35GC shows in vivo hepato-specific uptake. Radiotracer liver uptake profile follows reversible binding kinetics with data fitting to two-tissue compartmental (2T), and graphical Ichise multilinear analysis (MA2) with lower AIC and higher R² values, respectively. The study concludes that ^99mTc-Q9P35GC can be a robust radiotracer for noninvasive hepatocyte function assessment and diagnosis of liver fibrosis. Furthermore, its multifunctional properties enable it to be a promising platform for nanotheranostic applications. Full article

Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical composition, and/or chemical absorption. Depending on the targeted processes within the living organism, different tracers are used for various medical conditions, such as cancer, particular brain pathologies, cardiac events, and bone lesions, where the most commonly used tracers are radiolabeled with 18F (e.g., [¹⁸F]-FDG and NA [¹⁸F]). Oxygen-15 isotope is mostly involved in blood flow measurements, whereas a wide array of ¹¹C-based compounds have also been developed for neuronal disorders according to the affected neuroreceptors, prostate cancer, and lung carcinomas. In contrast, the single-photon emission computed tomography (SPECT) technique uses gamma-emitting radioisotopes and can be used to diagnose strokes, seizures, bone illnesses, and infections by gauging the blood flow and radio distribution within tissues and organs. The radioisotopes typically used in SPECT imaging are iodine-123, technetium-99m, xenon-133, thallium-201, and indium-111. This systematic review article aims to clarify and disseminate the available scientific literature focused on PET/SPECT radiotracers and to provide an overview of the conducted research within the past decade, with an additional focus on the novel radiopharmaceuticals developed for medical imaging. Full article

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [^99mTc]Tc-Sestamibi, [^99mTc]Tc-Tetrofosmin, and [^99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [^99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [^99mTc]Tc-Sestamibi and [^99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in ^99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies. Full article

Introduction. Primary hyperparathyroidism (PHPT) is a condition characterized by disorders of calcium–phosphate metabolism and bone metabolism caused by pathological overproduction of parathyroid hormone (PTH). The diagnosis of overt PHPT is based on the presence of clinical symptoms and laboratory abnormalities typical of this condition: hypercalcemia, hypercalciuria and elevated iPTH levels. Imaging studies are not used for diagnostic purposes; they are performed to localize the parathyroid glands prior to potential surgical treatment. Technetium 99 m sestamibi scintigraphy (Tc99 m-MIBI) is the gold standard in the assessment of pathologically altered parathyroid glands. Other diagnostic options include cervical ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). Parathyroid biopsy (P-FNAB) with iPTH washout concentration (iPTH-WC) assessment is still an underestimated method of preoperative parathyroid gland localization. Few studies have reported the utility of US-guided P-FNAB in preoperative assessment of parathyroid lesions. The aim of the study was to present our experience with 143 P-FNAB with iPTH-WC assessment. Material and methods. Laboratory results, US findings, P-FNAB complications and comparison with other imaging techniques were described and analyzed. Results. In 133 (93.0) patients, iPTH washout-to-serum ratio exceeded threshold level 0.5 and were classified as positive results. Median iPTH-WC in this group was 16,856 pg/mL, and the iPTH-WC to serum iPTH ratio was 158. There was no correlation between iPTH-WC and serum PTH, serum calcium, parathyroid gland volume and shape index. In the group of 46 operated patients, 44 demonstrated positive iPTH-WC results, which corresponds to a sensitivity of 95.6%. In Tc99-MIBI, radiotracer retention was found in 17 cases (in 24 MIBI performed), which corresponds to a sensitivity of 52.2%. P-FNAB did not cause any major side effects −92.5% of all patients had no or mild adverse events after this procedure. Conclusions. P-FNAB with iPTH-WC is a reliable method in parathyroid adenoma localization during PHPT. Its sensitivity for diagnosis of PHPT is much higher than that of Tc99-MIBI, and in some situations, P-FNAB with iPTH-WC may even replace that method. Furthermore, cost-effectiveness of iPTH-WC is at least similar to that of Tc99-MIBI. Complications of P-FNAB are mild and we can describe this method as a safe procedure. Full article

Auger electron-emitters increasingly attract attention as potential radionuclides for molecular radionuclide therapy in oncology. The radionuclide technetium-99m is widely used for imaging; however, its potential as a therapeutic radionuclide has not yet been fully assessed. We used MDA-MB-231 breast cancer cells engineered to express the human sodium iodide symporter-green fluorescent protein fusion reporter (hNIS-GFP; MDA-MB-231.hNIS-GFP) as a model for controlled cellular radionuclide uptake. Uptake, efflux, and subcellular location of the NIS radiotracer [^99mTc]TcO₄⁻ were characterised to calculate the nuclear-absorbed dose using Medical Internal Radiation Dose formalism. Radiotoxicity was determined using clonogenic and γ-H2AX assays. The daughter radionuclide technetium-99 or external beam irradiation therapy (EBRT) served as controls. [^99mTc]TcO₄⁻ in vivo biodistribution in MDA-MB-231.hNIS-GFP tumour-bearing mice was determined by imaging and complemented by ex vivo tissue radioactivity analysis. [^99mTc]TcO₄⁻ resulted in substantial DNA damage and reduction in the survival fraction (SF) following 24 h incubation in hNIS-expressing cells only. We found that 24,430 decays/cell (30 mBq/cell) were required to achieve SF_0.37 (95%-confidence interval = [SF_0.31; SF_0.43]). Different approaches for determining the subcellular localisation of [^99mTc]TcO₄⁻ led to SF_0.37 nuclear-absorbed doses ranging from 0.33 to 11.7 Gy. In comparison, EBRT of MDA-MB-231.hNIS-GFP cells resulted in an SF_0.37 of 2.59 Gy. In vivo retention of [^99mTc]TcO₄⁻ after 24 h remained high at 28.0% ± 4.5% of the administered activity/gram tissue in MDA-MB-231.hNIS-GFP tumours. [^99mTc]TcO₄⁻ caused DNA damage and reduced clonogenicity in this model, but only when the radioisotope was taken up into the cells. This data guides the safe use of technetium-99m during imaging and potential future therapeutic applications. Full article

This paper presents the application of ciprofloxacin as a biologically active molecule (vector) for delivering diagnostic radiopharmaceuticals to the sites of bacterial infection. Ciprofloxacin-based radioconjugates containing technetium-99m or gallium-68 radionuclides were synthesised, and their physicochemical (stability, lipophilicity) and biological (binding study to Staphylococcus aureus and Pseudomonas aeruginosa) properties were investigated. Both the tested radiopreparations met the requirements for radiopharmaceuticals, and technetium-99m-labelled ciprofloxacin turned out to be a good radiotracer for the tomography of diabetic foot syndrome using SPECT. Full article

The use of ordered mesoporous matrices, and in particular carbon-based mesoporous nanoparticles has shown great potential towards enhancing the bioavailability of orally administered drugs. Nevertheless, elucidation of the in vivo absorption, distribution, and excretion of such carriers is essential for understanding their behaviour, and radiolabelling provides a very useful way to track their occurrence inside the body. In this work, uniform spherical CMK-1-type ordered mesoporous carbon nanoparticles have been radiolabelled with Technetium-99m (^99mTc) and traced after oral administration to mice. Ex vivo biodistribution studies showed that the radiolabelled nanoparticles accumulated almost exclusively in the gastrointestinal tract; complete elimination of the radiotracer was observed within 24 h after administration, with practically no uptake into other main organs. These findings along with the results from in vitro stability studies indicate that the spherical carbon nanoparticles examined could be safely used as drug carriers with minimal side effects, but also support the great value of radiolabelling methods for monitoring the particles’ behaviour in vivo. Full article

Purpose: The purpose of this study was to assess the possibility of detecting sentinel lymph nodes (SLNs) and to perform analysis of lymphatic outflow in patients with suspicion of upper tract urothelial carcinoma (UTUC) with the use of a radioisotope-based technique. Methods: During 2018–2021, a prospective study was conducted on 19 patients with the suspicion of UTUC and for whom diagnostic ureterorenoscopy (URS) was planned. Technetium-99m (^99mTc) nanocolloid radioactive tracer injection and a tumor biopsy were performed for staging procedures. Three-dimensional (3D) reconstruction and fusion of images were performed for better localization of lymph nodes (LNs). Detection of SLNs and the analysis of the radiotracer outflow was conducted with the use of single-photon emission-computed tomography/computed tomography (SPECT/CT) lymphangiography. Results: The mean age of the patients was 73.4 years; 7 (36%) were male. Pathological staging from the biopsy was T0—8 (42%), Ta—7 (36%), T1—4 (21%). SLNs were detected in two of 19 cases (10%). In one patient a single SLN (5.3%) was visualized, and in another case (5.3%), multiple (double) radioactive lymph nodes were visualized. In 17 out of the 19 (89.5%) cases, no lymphatic outflow was observed, and out of these five cases (26.3%) of gravitational leakage of injected radiotracer to the retroperitoneal space was noted. Conclusions: We demonstrated that detection of SLNs in the upper urinary tract is possible yet challenging. Radiotracer injection in the upper urinary tract during ureterorenoscopy is difficult to perform, and the expected result of injection is unsatisfactory. Lymphatic outflow from the tumor site to the first LNs in our studied group of patients is visible in 10.5% of cases. SPECT/CT lymphangiography in cases of UTUC may provide valuable information about a patient’s individual anatomy of the lymphatic system and the position of the first lymph nodes draining lymph with potential metastatic cells from the tumor. Full article

Diagnostic imaging and radionuclide therapy of prostate (PC) and breast cancer (BC) using radiolabeled gastrin-releasing peptide receptor (GRPR)-antagonists represents a promising approach. We herein propose the GRPR-antagonist based radiotracer [^99mTc]Tc-DB15 ([^99mTc]Tc-N₄-AMA-DGA-_DPhe⁶,Sar¹¹,LeuNHEt¹³]BBN(6-13); N₄: 6-carboxy-1,4,8,11-tetraazaundecane, AMA: aminomethyl-aniline, DGA: diglycolic acid) as a new diagnostic tool for GRPR-positive tumors applying SPECT/CT. The uptake of [^99mTc]Tc-DB15 was tested in vitro in mammary (T-47D) and prostate cancer (PC-3) cells and in vivo in T-47D or PC-3 xenograft-bearing mice as well as in BC patients. DB15 showed high GRPR-affinity (IC₅₀ = 0.37 ± 0.03 nM) and [^99mTc]Tc-DB15 strongly bound to the cell-membrane of T-47D and PC-3 cells, according to a radiolabeled antagonist profile. In mice, the radiotracer showed high and prolonged GRPR-specific uptake in PC-3 (e.g., 25.56 ± 2.78 %IA/g vs. 0.72 ± 0.12 %IA/g in block; 4 h pi) and T-47D (e.g., 15.82 ± 3.20 %IA/g vs. 3.82 ± 0.30 %IA/g in block; 4 h pi) tumors, while rapidly clearing from background. In patients with advanced BC, the tracer could reveal several bone and soft tissue metastases on SPECT/CT. The attractive pharmacokinetic profile of [^99mTc]DB15 in mice and its capability to target GRPR-positive BC lesions in patients highlight its prospects for a broader clinical use, an option currently being explored by ongoing clinical studies. Full article

Curcumin is a natural occurring molecule that has aroused much interest among researchers over the years due to its pleiotropic set of biological properties. In the nuclear medicine field, radiolabelled curcumin and curcumin derivatives have been studied as potential radiotracers for the early diagnosis of Alzheimer’s disease and cancer. In the present review, the synthetic pathways, labelling methods and the preclinical investigations involving these radioactive compounds are treated. The studies entailed chemical modifications for enhancing curcumin stability, as well as its functionalisation for the labelling with several radiohalogens or metal radionuclides (fluorine-18, technetium-99m, gallium-68, etc.). Although some drawbacks have yet to be addressed, and none of the radiolabelled curcuminoids have so far achieved clinical application, the studies performed hitherto provide useful insights and lay the foundation for further developments. Full article

To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [^99mTc][Tc(I)]⁺ core to obtain [^99mTc]Tc-CN4NF and [^99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [^99mTc]Tc-CN4NF and [^99mTc]Tc-CN5NF were specific to bacteria. Compared with [^99mTc]Tc-CN4NF, biodistribution studies of [^99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [^99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [^99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [^99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer. Full article