sodium-pertechnetate-tc-99m and Neoplasms

Noninvasive bioluminescence imaging (BLI) of luciferase-expressing tumor cells has advanced pre-clinical evaluation of cancer therapies. Yet despite its successes, BLI is limited by poor spatial resolution and signal penetration, making it unusable for deep tissue or large animal imaging and preventing precise anatomical localization or signal quantification. To refine pre-clinical BLI methods and circumvent these limitations, we compared and ultimately combined BLI with tomographic, quantitative imaging of the sodium iodide symporter (NIS). To this end, we generated tumor cell lines expressing luciferase, NIS, or both reporters, and established tumor models in mice. BLI provided sensitive early detection of tumors and relatively easy monitoring of disease progression. However, spatial resolution was poor, and as the tumors grew, deep thoracic tumor signals were massked by overwhelming surface signals from superficial tumors. In contrast, NIS-expressing tumors were readily distinguished and precisely localized at all tissue depths by positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging. Furthermore, radiotracer uptake for each tumor could be quantitated noninvasively. Ultimately, combining BLI and NIS imaging represented a significant enhancement over traditional BLI, providing more information about tumor size and location. This combined imaging approach should facilitate comprehensive evaluation of tumor responses to given therapies.

Topics: Animals; Benzothiazoles; Cell Line, Tumor; Female; Genes, Reporter; Humans; Luciferases, Firefly; Luminescent Measurements; Mice; Molecular Imaging; Neoplasms; Positron-Emission Tomography; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Symporters; Tomography, Emission-Computed, Single-Photon; Xenograft Model Antitumor Assays

Imaging spontaneous cancer cell metastasis or heterogeneous tumor responses to drug treatment in vivo is difficult to achieve. The goal was to develop a new highly sensitive and reliable preclinical longitudinal in vivo imaging model for this purpose, thereby facilitating discovery and validation of anticancer therapies or molecular imaging agents.. The strategy is based on breast cancer cells stably expressing the human sodium iodide symporter (NIS) fused to a red fluorescent protein, thereby permitting radionuclide and fluorescence imaging. Using whole-body nano-SPECT/CT with (99m)TcO4(-), we followed primary tumor growth and spontaneous metastasis in the presence or absence of etoposide treatment. NIS imaging was used to classify organs as small as individual lymph nodes (LNs) to be positive or negative for metastasis, and results were confirmed by confocal fluorescence microscopy. Etoposide treatment efficacy was proven by ex vivo anticaspase 3 staining and fluorescence microscopy.. In this preclinical model, we found that the NIS imaging strategy outperformed state-of-the-art (18)F-FDG imaging in its ability to detect small tumors (18.5-fold-better tumor-to-blood ratio) and metastases (LN, 3.6-fold) because of improved contrast in organs close to metastatic sites (12- and 8.5-fold-lower standardized uptake value in the heart and kidney, respectively). We applied the model to assess the treatment response to the neoadjuvant etoposide and found a consistent and reliable improvement in spontaneous metastasis detection. Importantly, we also found that tumor cells in different microenvironments responded in a heterogeneous manner to etoposide treatment, which could be determined only by the NIS-based strategy and not by (18)F-FDG imaging.. We developed a new strategy for preclinical longitudinal in vivo cancer cell tracking with greater sensitivity and reliability than (18)F-FDG PET and applied it to track spontaneous and distant metastasis in the presence or absence of genotoxic stress therapy. Importantly, the model provides sufficient sensitivity and dynamic range to permit the reliable assessment of heterogeneous treatment responses in various microenvironments.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; DNA Damage; Environment; Etoposide; Female; Fluorescence; Humans; Lymph Nodes; Microscopy, Confocal; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasms; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sodium Pertechnetate Tc 99m; Symporters; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Whole Body Imaging

Recent data suggest that somatostatin receptors (SSTRs) are expressed on various tumor cells. High-level expression of SSTR on the tumor cell surface provides the basis for the successful clinical use of radiolabeled ligands for the in vivo localization of tumor sites. We have characterized the in vitro binding properties of the novel SSTR ligand 99mTc-P829 using primary human tumors (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small cell and non-small cell lung cancer, and melanomas; n = 28), various tumor cell lines, and COS7 cells transfected with the human SSTR (hSSTR) subtypes 1, 2, 3, 4, and 5. 99mTc-P829 bound to primary tumor cells and tumor cell lines with high affinity and high capacity. The dissociation constants (Kd) ranged between 1 and 20 nM. 99mTc-P829 also bound with high affinity to the transfected hSSTR2 (Kd, 2.5 nM), hSSTR5 (Kd, 2 nM), and hSSTR3 (Kd, 1.5 nM). Binding of 99mTc-P829 to hSSTR3 was found to be displaceable by unlabeled P829/([ReO]-P829), SST-14, and vasoactive intestinal peptide (VIP; IC50, 2 nM) and, less effectively, by Tyr3-octreotide (IC50, 20 nM). In contrast, the binding of 99mTc-P829 to hSSTR2 and hSSTR5 could be displaced by P829/([ReO]-P829) and Tyr3-octreotide but not by VIP. 99mTc-P829 scintigraphy revealed in vivo binding to primary or metastatic tumor sites in seven of eight patients with breast cancer and six of six patients with melanoma. In summary, our data show that 99mTc-P829 binds with high affinity to many different types of primary and cloned tumor cells. Furthermore, our data identify hSSTR2, the VIP acceptor hSSTR3, and hSSTR5 as the respective target receptors. Because these receptors are frequently expressed at high levels on primary tumor cells, 99mTc-P829 appears to be a promising novel peptide tracer for tumor imaging.

Topics: Animals; Binding, Competitive; Blotting, Northern; Breast Neoplasms; COS Cells; Female; Humans; Melanoma; Neoplasms; Peptides, Cyclic; Radioligand Assay; Receptors, Somatostatin; RNA, Messenger; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed, Single-Photon; Tumor Cells, Cultured

Radionuclide ventriculography (RNV) is an established method of evaluating cardiotoxic side-effects of chemotherapy. The image quality of RNV depends on labelling yields obtained after red blood cell (RBC) labelling with 99Tc(m)-pertechnetate and has an influence on the evaluation of the left ventricular ejection fraction (LVEF). Several drugs and certain parameters of RBC labelling are known to have a detrimental effect on the labelling yield, but often the reason for poor image quality remains unclear. The aim of this study was to determine the effect of chemotherapeutic agents on LVEF evaluation. The chemotherapeutic medications and RNV data of 116 patients were noted. The patients underwent 205 RNV examinations (up to 7 RNV follow-up examinations) consisting of rest and stress studies. Ten patients with a poor labelling yield after in vivo labelling received an additional RNV study after in vitro labelling. The effects of commonly used anticoagulants and chemotherapeutic drugs on labelling yields were also investigated in experiments on in vitro RBC labelling. In vitro labelling had the advantage of better detection of pathological alterations in left ventricular motility, but often improved evaluability only slightly. The administration of corticosteroids showed an unexpected positive correlation with image quality (Spearman correlation coefficient: prednisone, 0.42403, P = 0.0013; prednisolone, 0.45629, P = 0.0286) and labelling yield (prednisolone, 0.65466, P = 0.0024), whereas idarubicin showed a negative correlation with image quality (-0.53364, P = 0.005). A slight positive correlation of prednisolone with LVEF at rest (0.45425, P = 0.0197) was also noted. Using our evaluation software, the manual contour method was found to be superior to the automatic determination of the left ventricular contour. Cycle ergometry alone caused a significant deterioration in image quality. The in vitro results suggested a negative influence of epirubicine on labelling yields at very high concentrations (10(-3) M). Our main result was that a clinically adequate study is possible in patients with moderate image quality and labelling yields. Furthermore, the administration of corticosteroids had a positive impact on image quality.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Exercise Test; Female; Gated Blood-Pool Imaging; Heart; Humans; Male; Middle Aged; Neoplasms; Prednisolone; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Sodium Pertechnetate Tc 99m; Statistics, Nonparametric; Ventricular Function, Left

The aim of our study was to evaluate the clinical value of immunoscintigraphy with the monoclonal antibody 99mTc-BW 250/183 in patients with fever of unknown origin (FUO). The antibody BW 250/183 is an immunoglobulin G1 subtype that binds to the antigen NCA-95, which is expressed on the cell membrane surface of granulocytes.. We studied 51 patients who were referred with the diagnosis of FUO. Thirty-five percent of the patients suffered from infection, 17% had autoimmune diseases, 14% had neoplasms and 8% had other diseases. The remaining 28% of the patients did not have a diagnosis. Planar imaging was performed in all patients, and 19 patients underwent SPECT. In our analysis, both cold and hot spots were considered diagnostic.. Pyogenic infections were visualized correctly in 13 foci. The diagnosis of endocarditis (n = 4) could be determined only by SPECT. False-negative results were found in 4 patients and false-positive uptake was seen in 2 patients. No false-positive uptake or cold spots in the central bone marrow were found in patients with viral, granulomatous and autoimmune diseases or in those patients in whom no FUO cause was found in a 6-mo follow-up. In these patients, a negative scan did not change their diagnostic work-up. Cold spots in the central bone marrow were correctly interpreted in 5 of 6 patients. Sensitivity in detecting pyogenic foci was 73% and specificity was 97%. Positive and negative predictive values were 93% and 87%, respectively. Including areas of decreased uptake in the analysis, sensitivity for detecting an underlying inflammatory or malignant process for FUO was 81 % and specificity was 87%. Positive and negative predictive values were 81% and 87%, respectively.. Immunoscintigraphy with 99mTc-BW 250/183 in patients with FUO has clinical potential for the diagnosis and exclusion of pyogenic causes of FUO. Metastatic malignant disease and high-grade spondylodiskitis could be diagnosed early in a diagnostic work-up by a characteristic cold spot pattern in the bone marrow. SPECT is indispensible for scintigraphic imaging of endocarditis.

Topics: Adult; Antibodies, Monoclonal; Autoimmune Diseases; Female; Fever of Unknown Origin; Humans; Infections; Leukocytes; Male; Neoplasms; Predictive Value of Tests; Radioimmunodetection; Radiopharmaceuticals; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed, Single-Photon

The authors indicate that according to the degree of informative value all the methods used in this study can be listed as follows: the method of combined use of positive and negative scintigraphy, the method of positive scintigraphy with Ga67-citrate (the lymph nodes above the diaphragm) and Tc99-pertechnetate (the lymph nodes below the diaphragm), the method of indirect lymphography with colloids. The main indices of the radionuclide methods in the diagnosis of the lymph node metastatic involvement are presented.

Topics: Female; Gallium Radioisotopes; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasms; Radionuclide Imaging; Sodium Pertechnetate Tc 99m

The pharmacokinetics, organ distribution, and 24-hr urinary excretion of negatively charged 99mTc-labeled multilamellar liposomes, composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7:3 molar ratio, were studied in seven patients with cancer. The radiolabeled liposomes were administered i.v. in three doses: 150 mg/sq m of body surface area; 300 mg/sq m; and 450 mg/sq m of lipid. The dose of 99mTc was 4.8 to 7.6 mCi per patient. The plasma disappearance curve was biphasic (half-life alpha = 5.53 min, half-life beta = 289 min), suggesting a two-compartmental model of distribution. The calculated volume of distribution indicated considerable tissue retention of liposomes. This was confirmed by body imaging. Twenty-four hr after injection, liposomes were localized in organs rich in reticuloendothelial cells, i.e., liver [44.5 +/- 9.1% (S.E.)], spleen [25.5 +/- 7.7%], lung [14.5 +/- 4.9%], and bone marrow. Although the hepatic uptake accounted for more than 40% of the total uptake, the spleen retained liposomes at a higher density. Cumulative urinary excretion of radioactivity was 13.4 +/- 1.5% over 24 hr. Liposome administration was safe and devoid of any adverse side effects. The results provide a basis for the use of liposomes as potential target-specific and safe drug carriers in the treatment of pathological conditions that involve organs rich in reticuloendothelial cells.

Topics: Adult; Female; Humans; Kinetics; Liposomes; Male; Metabolic Clearance Rate; Middle Aged; Neoplasms; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Tissue Distribution

The subtraction method for radioimmunodetection (RID) of cancer is showing potential as a diagnostic tool. An objective assessment of this technique is needed in order to determine its clinical usefulness. A numerical analysis of the RID scintigrams was developed and applied to 21 RID studies on 20 patients for whom a final diagnosis had been established. The subtraction technique was shown to give rise to artifactual positive regions, which could be avoided by experienced clinicians. When artifact-producing regions were excluded, 97 regions were examined (80 nontumor, 17 tumor-containing). The "background" scintigrams were shown to be good models for nontumor regions of the antibody scintigrams, and tumor and nontumor regions were shown to form statistically distinct groups.

Topics: Antibodies; Carcinoembryonic Antigen; Humans; Iodine Radioisotopes; Neoplasms; Radionuclide Imaging; Serum Albumin; Sodium Pertechnetate Tc 99m; Statistics as Topic; Subtraction Technique; Technetium; Technetium Tc 99m Aggregated Albumin

Topics: Adolescent; Adult; alpha-Fetoproteins; Antibodies, Neoplasm; Carcinoembryonic Antigen; Female; Humans; Iodine Radioisotopes; Isotope Labeling; Male; Neoplasm Metastasis; Neoplasms; Radionuclide Imaging; Serum Albumin; Sodium Pertechnetate Tc 99m; Subtraction Technique; Technetium; Technetium Tc 99m Aggregated Albumin; Thyroglobulin

A dual radionuclide subtraction technique for external detection of tumours has been evaluated to determine the viability of the method for use with radioisotope labelled antibodies. A number of external scintigraphic investigations have been carried out with 131I-labelled antibodies to carcinoembryonic antigen (CEA). The investigations were performed on patients with metastatic disease known to produce CEA. The dual radionuclide subtraction technique was used to account for the blood and tissue background. The 131I-labelled antibodies were found to localise in the metastatic lesions, but the subtraction technique using 99Tcm-labelled HSA and pertechnetate gave ambiguous results, which included the production of artefacts. The ambiguities noted in the clinical results were substantiated by experimental data, which highlight the unreliability of this technique.

Topics: Antibodies, Neoplasm; Carcinoembryonic Antigen; Female; Humans; Iodine Radioisotopes; Neoplasm Metastasis; Neoplasms; Radionuclide Imaging; Serum Albumin; Sodium Pertechnetate Tc 99m; Subtraction Technique; Technetium; Technetium Tc 99m Aggregated Albumin

Topics: Adolescent; Child; Child, Preschool; Diagnosis, Differential; Diphosphates; Female; Humans; Infant; Male; Neoplasms; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Heart; Heart Failure; Humans; Neoplasms; Pericardial Effusion; Pericarditis, Tuberculous; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium

Topics: Astrocytoma; Brain; Brain Neoplasms; Chlormerodrin; Diuretics; Glioma; Neoplasms; Organomercury Compounds; Radionuclide Imaging; Serum Albumin; Serum Albumin, Radio-Iodinated; Sodium Pertechnetate Tc 99m; Technetium