Detection of melanoma, breast cancer and head and neck squamous cell cancer sentinel lymph nodes by Tc-99m Tilmanocept (Lymphoseek®)

Technetium-99m-labeled Tilmanocept or Lymphoseek® (Cardinal Health, Dublin, Ohio) is a soluble, synthetic molecule with a small diameter (7 nm), which is comprised of technetium-99m chelated to a dextran backbone containing multiple units of mannose ligands with a high affinity for CD206, a receptor located on the surface of macrophages and dendritic cells that are found in high concentration in lymph nodes. It enables quick transit from the injection site and rapid lymph node accumulation. The binding of mannose ligand and CD206 results in the internalization of the ligand and receptor into the cell. Once the Technetium-99m-labeled Tilmanocept (Lymphoseek®) reaches the lymph node, it is readily internalized by the macrophages and dendritic cells within the draining lymph nodes. Technetium-99m-labeled Tilmanocept (Lymphoseek®) has been extensively studied as a radioisotope for detection of sentinel lymph nodes in melanoma, breast cancer and head and neck squamous cell carcinoma in clinical trials. Based on its safety and ability to detect sentinel lymph nodes satisfactorily, it has been approved by the FDA to use as a radioisotope for preoperative lymphoscintigraphy for identification of sentinel lymph nodes in these types of cancer. Further, the FDA has expanded approval of Technetium-99m-labeled for sentinel lymph node mapping of all solid tumors as well as in pediatric patients.

Relationship of In Vitro Toxicity of Technetium-99m to Subcellular Localisation and Absorbed Dose

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 SF0.37 (95%-confidence interval = [SF0.31; SF0.43]). Different approaches for determining the subcellular localisation of [99mTc]TcO4− led to SF0.37 nuclear-absorbed doses ranging from 0.33 to 11.7 Gy. In comparison, EBRT of MDA-MB-231.hNIS-GFP cells resulted in an SF0.37 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.

Physicochemical and Biological Study of 99mTc and 68Ga Radiolabelled Ciprofloxacin and Evaluation of [99mTc]Tc-CIP as Potential Diagnostic Radiopharmaceutical for Diabetic Foot Syndrome Imaging

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.

Biodistribution of Mesoporous Carbon Nanoparticles via Technetium-99m Radiolabelling after Oral Administration to Mice

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.

Diagnosis of Cardiac Transthyretin Amyloidosis by Technetium-99m Pyrophosphate Heart Scan, Confirmed by Genetic Mutations: Case Report

Amyloid deposition in the myocardium can cause clinically significant heart failure, which is very difficult to diagnose. The present case reported presented a patient with heart failure, with suspected cause of cardiac amyloidosis, but abdominal fat pad and endomyocardial with Congo red stain biopsies were negative. Due to high suspicion of cardiac amyloidosis, a technetium-99m pyrophosphate (Tc-99m PYP) heart scan was done, which was revealed as strongly suggestive for cardiac transthyretin amyloidosis. So, the patient was sent for genetic testing, and a TTR gene mutation [c.148G>A (p.Val50Met)] was found. Keywords: Cardiac amyloidosis; Endomyocardial biopsy (EMB); Technetium-99m pyrophosphate (Tc-99m PYP) heart scan; Transthyretin amyloidosis (TTR)

Recent Progress in Technetium-99m-Labeled Nanoparticles for Molecular Imaging and Cancer Therapy

Nanotechnology has played a tremendous role in molecular imaging and cancer therapy. Over the last decade, scientists have worked exceptionally to translate nanomedicine into clinical practice. However, although several nanoparticle-based drugs are now clinically available, there is still a vast difference between preclinical products and clinically approved drugs. An efficient translation of preclinical results to clinical settings requires several critical studies, including a detailed, highly sensitive, pharmacokinetics and biodistribution study, and selective and efficient drug delivery to the target organ or tissue. In this context, technetium-99m (99mTc)-based radiolabeling of nanoparticles allows easy, economical, non-invasive, and whole-body in vivo tracking by the sensitive clinical imaging technique single-photon emission computed tomography (SPECT). Hence, a critical analysis of the radiolabeling strategies of potential drug delivery and therapeutic systems used to monitor results and therapeutic outcomes at the preclinical and clinical levels remains indispensable to provide maximum benefit to the patient. This review discusses up-to-date 99mTc radiolabeling strategies of a variety of important inorganic and organic nanoparticles and their application to preclinical imaging studies.

EVALUATION OF EXTENT OF BREAST CANCER IN A PATIENT WITH HER2/NEU OVEREXPRESSION USING A RADIOPHARMACEUTICAL BASED ON TECHNETIUM-99M-LABELED TARGET MOLECULES (CASE REPORT)

Introduction. Overexpression of Her2/neu is detected in 15–20 % of patients with breast cancer and associated with an aggressive form of disease and low overall and disease-free survival rates. Currently, immunohistochemical studies (IHC) and methods of in situ hybridization are used to assess Her2/neu status. One of significant drawbacks of this detection is the impossibility of simultaneous assessment of the receptor status of the primary tumor and metastatic sites. The increasing popularity of radionuclide methods using recombinant proteins as a targeting module have already demonstrated their effectiveness in solving this question at the initial stages of clinical research.The purpose of this study is to demonstrate a clinical case of assessing the extent of breast cancer in a patient with overexpression of Her2/neu using a radiopharmaceutical based on targeted protein molecules labeled with technetium-99m.Description of the clinical case. A patient diagnosed with stage IIIA right breast cancer (T2N2M0), multicentric growth and metastases in right axillary and subclavian lymph nodes at the diagnostic stage was injected intravenously with 99mTc-ADAPT6 radiopharmaceutical. The drug was prepared in the Department of Nuclear Medicine of Research Cancer Institute (Tomsk) immediately before its administration. Planar scintigraphy and singlephoton emission tomography of the chest organs were performed 2 hours after injection of 99mTc-ADAPT6 radiopharmaceutical. In addition to the previously described tumors, 3 foci of hyperfixation of the tracer in the projection of the 5th rib on the right along the middle-clavicular line, as well as in the projection of the 8 and 9 thoracic vertebrae (Th VIII, IX) were found. Computed tomography of the chest organs and bone scintigraphy with 99mTc-pyrophosphate showed no metastases in the 5th rib on the right and Th VIII, IX. Magnetic resonance imaging of the thoracic spine revealed 2 metastatic foci in Th VIII, IX. Planar scintigraphy with 99mTc-pyrophosphate and CT performed 6 months after injection of 99mTc-ADAPT6 revealed previously described foci in the projection of the thoracic spine (Th VIII, IX) and 5 ribs on the right along the mid-clavicular line. Conclusion. The results demonstrated during the study suggest that 99mTc-ADAPT6 is a promising tracer for molecular imaging of tumor foci with overexpression of the Her2/neu receptor in breast cancer patients.