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- Carlsson, Jörgen, et al.
(författare)
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Conjugate chemistry and cellular processing of EGF-dextran
- 1999
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:3, s. 313-321
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Tidskriftsartikel (refereegranskat)abstract
- Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.
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| 10. |
- Kälkner, Karl-Mikael, et al.
(författare)
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Positron emission tomography (PET) with 11C-5-hydroxytryptophan (5-HTP) in patients with metastatic hormone-refractory prostatic adenocarcinoma
- 1997
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 24:4, s. 319-325
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma has opened a potentially new therapeutic approach in this group of patients with a poor prognosis and few effective therapy modalities. Based on previous findings of increased uptake of 11C-5-hydroxytryptophan (11C-5-HTP) in neuroendocrine tumours using the PET technique, this tracer was applied in the study of 10 patients with metastatic hormone-refractory prostatic adenocarcinoma. In three patients, the study was repeated after treatment. An increased uptake of 11C-5-HTP was observed in all investigated skeletal lesions, although the magnitude of the uptake was moderate. The difference between the standard uptake values (SUV) in normal bone and metastatic lesions was significant (p < 0.001). A kinetic analysis of the uptake of 11C-5-HTP demonstrates an increase during the first minutes followed by a wash-out and a stabilization of the tissue/blood ratio at about 2. The Patlak plots demonstrated a gradual increase in the transport rate during the first 20 to 30 min, after which a constant level was observed. The SUV varied between patients and between lesions over time and treatment. The uptake of 11C-5-HTP discriminates metastatic lesions from normal bone and may thus aid in the diagnosis and, potentially, in treatment monitoring of metastatic hormone-refractory prostatic adenocarcinoma. Uptake kinetics are characterized by a wash-out and cannot alone be used as proof of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma.
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| 12. |
- Lubberink, Mark, et al.
(författare)
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Positron emission tomography and radioimmunotargeting : aspects ofquantification and dosimetry
- 1999
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:3, s. 343-349
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography (PET) is a medical imaging tool with high resolution and good quantitative properties, which makes it suitable for in vivo quantification of radioimmunotargeting agents. Most radionuclides used in radioimmunotherapy have positron-emitting analogues, which can be used for PET imaging, and this opens the possibility of performing dosimetry with PET. These isotopes, however, often emit gamma radiation and high-energy positrons in their decay, influencing the imaging properties of PET. Spatial resolution, reconstructed background and line source recovery for a number of non-pure positron emitters were investigated and compared with the imaging properties of 18F. PET imaging properties did not degrade severely for these non-pure positron emitters, but caution has to be applied when doing quantitative measurements. To assess the possibility of conducting PET studies during therapy, by combining, for example, a small amount of 124I with 131I, the influence of the presence of large amounts of gamma radiation on PET count rate characteristics was studied. The results of these studies were related to the necessary amounts of radioactivity needed for treatment of post-operative remains of glioma. The results indicate that the count rate capabilities of 2D PET permit PET studies for dose evaluation during radioimmunotherapy.
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| 13. |
- Lundqvist, Hans, et al.
(författare)
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Positron emission tomography and radioimmunotargeting : general aspects
- 1999
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:3, s. 335-341
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Tidskriftsartikel (refereegranskat)abstract
- To optimize radioimmunotherapy, in vivo information on individual patients, such as radionuclide uptake, kinetics, metabolic patterns and optimal administration methods, is important. An overriding problem is to determine accurately the absorbed dose in the target organ as well as critical organs. Positron Emission Tomography (PET) is a superior technique to quantify regional kinetics in vivo with a spatial resolution better than 1 cm3 and a temporal resolution better than 10 s. However, target molecules often have distribution times of several hours to days. Conventional PET nuclides are not applicable and alternative positron-emitting nuclides with matching half-lives and with suitable labelling properties are thus necessary. Over many years we have systematically developed convenient production methods and labelling techniques of suitable positron nuclides, such as 110In(T(1/2) = 1.15 h), 86Y(T(1/2) = 14 h), 76Br(T(1/2) = 16 h) and 124I(T(1/2) = 4 days). 'Dose planning' can be done, for example, with 86Y- or 124I-labelled ligands before therapy, and 90Y- and 131I-labelled analogues and double-labelling, e.g. with a 86Y/90Y-labelled ligand, can be used to determine the true radioactivity integral from a pure beta-emitting nuclide. The usefulness of these techniques was demonstrated in animal and patient studies by halogen-labelled MAbs and EGF-dextran conjugates and peptides chelated with metal ions.
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- Skogseid, Britt, et al.
(författare)
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Limited tumor involvement found at multiple endocrine neoplasia type I pancreatic exploration : can it be predicted by preoperative tumor localization?
- 1998
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 22:7, s. 673-677; discussion 667-668
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Tidskriftsartikel (refereegranskat)abstract
- Radiologically demonstrable pancreatic endocrine tumors are a frequent requirement for exploration in patients with multiple endocrine neoplasia type I (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of pancreatic endocrine metastases. This study explores biochemical tumor markers and operative findings in relation to preoperative pancreatic radiology in 25 MEN-I patients. They underwent pancreatic surgery with (n = 19) or without (n = 6) radiologic signs of primary tumor and absence of metastases upon conventional examination, including OctreoScan testing (n = 10). Biochemical diagnosis required an increasing elevation of at least two independent pancreatic tumor markers. Tumor diameters averaged 1.1 cm (0-5 cm) and 0.9 cm (0.2-1.5 cm) in the patients with and without positive preoperative radiology, respectively. These investigations never displayed more than one of the consistently multiple tumors, and the results were falsely positive in 26%. Preoperatively unidentified regional or hepatic metastases were found at surgical exploration in 26% of patients with radiologic localization and in none of the others. Limited pancreatic tumor involvement necessitated intraoperative absence of metastases and pancreatic lesions /= 7 mm in diameter. Conventional pancreatic imaging is insensitive and nonspecific for recognizing even substantial pancreatic tumors associated with MEN-I.
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