![Representative in vivo [ 99m Tc]-AP39-SPECT imaging in apoE-/-and WT mice. A) In vivo [ 99m Tc]-AP39-SPECT imaging of an apoE-/(left) and a WT mouse (sagittal and transversal reconstruction, upper and lower panel, respectively). Imaging data are displayed in false colors as a maximum intensity projection (MIP). The color-bar reflects normalized intensity of the SPECT dataset, displaying the lowest (0) and highest (1) value in black and red, respectively. To stress signal differences in the aortic region, the slice with highest signal intensity in the chest is displayed (lower panel). This slice was overlaid with a manually performed MRI scan (informative only). Using volumic MRI and SPECT datasets, overall anatomy was matched. Processing steps involved rotation and scaling of the SPECT data to match the FOV of the MRI data. The closest MRI slice was overlaid to the SPECT slice. Injected activity of [ 99m Tc]-AP39 was 144-159 MBq, timing of the SPECT scan was 4 hours after [ 99m Tc]-AP39 injection, the collection period was 25 min, and rompun/ketamin was used for anaesthesia; B) in vivo SPECT signal intensity 4 hours after [ 99m Tc]-AP39 injection in the aortic artery of apoE-/-and WT mice (N.=5, each; cpm/cm 3 ); C) resected aortas (from root to the bifurcation) were weighed and placed into a g-counter. [ 99m Tc]-AP39 uptake is stated as %ID per gram of harvested aorta in apoE-/-and WT mice (N.=5, each).](https://www.researchgate.net/profile/Richard-P-Baum/publication/274902173/figure/fig14/AS:614148807344167@1523435894962/Representative-in-vivo-99m-Tc-AP39-SPECT-imaging-in-apoE--and-WT-mice-A-In-vivo_Q320.jpg)
![[Lys 40 (Ahx-HYNIC-99m Tc/EDDA)NH 2 ]-exendin-4 SPECT/ CT of the 16-year-old man with signs and symptoms of insulinoma. Examination revealed a pathological focal uptake of the tracer in the pancreas (arrow).](https://www.researchgate.net/profile/Richard-P-Baum/publication/274902173/figure/fig5/AS:614148807327749@1523435894157/Lys-40-Ahx-HYNIC-99m-Tc-EDDANH-2-exendin-4-SPECT-CT-of-the-16-year-old-man-with_Q320.jpg)
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The long history of the International Research Group in Immuno-Scintigraphy and Therapy (IRIST)
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Background:
Poorly differentiated thyroid carcinoma (PDTC) and anaplastic (undifferentiated) thyroid carcinoma (ATC) comprise a small subset of thyroid tumors that are associated with a poor prognosis and account for a significant portion of the morbidity and mortality related to thyroid cancer. Since management strategies vary between these two entities, it is important for clinicians to be able to differentiate PDTC from ATC.
Methods:
We reviewed the literature on PDTC and ATC and compared clinical and histopathologic features important in defining the disease process.
Results:
Both PDTC and ATC display aggressive behavior with increased locoregional and distant disease. In most cases, patients are older and have large, locally advanced tumors. PDTC may represent an intermediate entity in the progression of well-differentiated thyroid carcinoma to ATC. The use of surgical management may be curative or palliative and differs between PDTC and ATC. The roles of radiotherapy and chemotherapy have not been well described.
Conclusions:
PDTC and ATC are rare diseases that carry a poor prognosis. Recognition of their different clinicopathologic features is important to the optimal management of these tumors.
2531 Background: L19-IL2 is a tumor-targeting immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a marker of tumor angiogenesis, and of human interleukin-2 (IL2). L19-IL2 is able to selectively deliver IL2 to tumor tissues exploiting the expression of EDB on newly formed blood vessels. The recommended monotherapy dose (RD) of 22.5 MioIU IL2 equivalents (day 1, 3, and 5) of L19-IL2 was defined earlier. In this study, we investigated L19-IL2 in combination with dacarbazine in patients with metastatic melanoma, assessing safety, tolerability, and activity. Methods: The study consists of a dose confirmation part, during which 10 patients with metastatic melanoma were enrolled, followed by a fixed dose part, during which 22 chemo-naive metastatic melanoma patients were treated at the RD. Patients received intravenous infusions of L19-IL2 (10, 15 and 22.5 MioIU during dose confirmation, and 22.5 MioIU in the fixed dose part of the study) on day 1, 3 and 5 in combination w...
The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor-node-metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.
Abstract
Purpose: The rationale of the present study was to radiolabel rituximab with 99m-technetium and to image B lymphocytes infiltration in the affected tissues of patients with chronic inflammatory autoimmune diseases, in particular, the candidates to be treated with unlabelled rituximab, in order to provide a rationale for 'evidence-based' therapy.
Procedures: Rituximab was labelled with (99m)Tc via 2-ME reduction method. In vitro quality controls of (99m)Tc-rituximab included stability assay, cysteine challenge, SDS-PAGE, immunoreactive fraction assay and competitive binding assay on CD20+ve Burkitt lymphoma-derived cells. For the human pilot study, 350-370 MBq (100 μg) of (99m)Tc-rituximab were injected in 20 patients with different chronic inflammatory autoimmune diseases. Whole body anteroposterior planar scintigraphic images were acquired 6 and 20 h p.i.
Results: Rituximab was labelled to a high labelling efficiency (>98%) and specific activity (3515-3700 MBq/mg) with retained biochemical integrity, stability and biological activity. Scintigraphy with (99m)Tc-rituximab in patients showed a rapid and persistent spleen uptake, and the kidney appeared to be a prominent source for the excretion of radioactivity. Inflamed joints showed a variable degree of uptake at 6 h p.i. in patients with rheumatoid arthritis indicating patient variability; similarly, the salivary and lacrimal glands showed variable uptake in patients with Sjögren's syndrome, Behçet's disease and sarcoidosis. Inflammatory disease with particular characteristics showed specific uptake in inflammatory lesions, such as, dermatopolymyositis patients showed moderate to high skin uptake, a sarcoidosis patient showed moderate lung uptake, a Behçet's disease patient showed high oral mucosa uptake and a polychondritis patient showed moderate uptake in neck cartilages. In one patient with systemic lupus erythematosus, we did not find any non-physiological uptake.
Conclusion: Rituximab can be efficiently labelled with (99m)Tc with high labelling efficiency. The results suggest that this technique might be used to assess B lymphocyte infiltration in affected organs in patients with autoimmune diseases; this may provide a rationale for anti-CD20 therapies.
Purification and amino acid sequence analysis of a proteolytic fragment of fibronectin (FN) from transformed human cells demonstrated that a high percentage of these FN molecules contains an extra amino acid sequence which is present only in a very low percentage of FN molecules from normal fibroblasts and is undetectable in plasma FN. This new amino acid sequence introduces into the FN molecule a site very sensitive to a number of proteolytic enzymes. By analyzing the cellular mRNA and genomic clones, we have demonstrated that this sequence derives from a differential splicing pattern of the FN mRNA precursors, which leads in transformed cells to a high‐level expression of an extra type III homology repeat (ED‐B) coded for by a previously unobserved exon. Here we also report the complete sequence of this new exon. These results demonstrate that in malignant cells the mechanisms regulating the splicing of FN mRNA precursors are altered.
PURPOSE: Variable uptake of the glucose analog ¹⁸ fluorodeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared ¹⁸ FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms.
PATIENTS AND METHODS: Preoperative ¹⁸ FDG-PET scans were performed in 55 patients. ¹⁸ FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1α); vascular endothelial growth factor (VEGF 165 ); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed.
RESULTS: There were positive correlations between ¹⁸ FDG uptake and Glut-1 expression (P < .001), MAI (P = .001), amount of necrosis (P = .010), number of tumor cells/volume (P = .009), expression of HK I (P = .019), number of lymphocytes (P = .032), and microvessel density (r = .373; P = .005). HIF-1α, VEGF 165 , HK II, HK III, and macrophages showed no univariate correlation with ¹⁸ FDG. In logistic regression, however, HIF-1α and HK II added value to MAI and Glut-1.
CONCLUSION: ¹⁸ FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of ¹⁸ FDG into the cell, HK for entering ¹⁸ FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1α for upregulating Glut-1. Together, these features explain why breast cancers vary in ¹⁸ FDG uptake and elucidate the low uptake in lobular breast cancer.
The availability of quantitative three-dimensional in vivo data on radionuclide distributions within the body makes it possible to calculate the corresponding nonuniform distribution of radiation absorbed dose in body organs and tissues. This pamphlet emphasizes the utility of the MIRD schema for such calculations through the use of radionuclide S values defined at the voxel level. The use of both dose point-kernels and Monte Carte simulation methods is also discussed. PET and SPECT imaging can provide quantitative activity data in voxels of several millimeters on edge. For smaller voxel sizes, accurate data cannot be obtained using present imaging technology. For submillimeter dimensions, autoradiographic methods may be used when tissues are obtained through biopsy or autopsy. Sample S value tabulations for five radionuclides within cubical voxels of 3 mm and 6 mm on edge are given in the appendices to this pamphlet. These S values may be used to construct three-dimensional dose profiles for nonuniform distributions of radioactivity encountered in therapeutic and diagnostic nuclear medicine. Data are also tabulated for I-131 in 0.1-mm voxels for use in autoradiography. Two examples illustrating the use of voxel S values are given, followed by a discussion of the use of three-dimensional dose distributions in understanding and predicting biologic response.
