Recent years have seen important changes in pharmacology. New techniques have been developed which are increasingly aimed at smaller groups of patients or even individual patients. In the past, thousands of chemical molecules were tested on a potential molecular target and the most effective molecules were selected.
View Article and Find Full Text PDFBackground: Red bone marrow (RBM) toxicity is dose-limiting in (pretargeted) radioimmunotherapy (RIT). Previous blood-based and two-dimensional (2D) image-based methods have failed to show a clear dose-response relationship. We developed a three-dimensional (3D) image-based RBM dosimetry approach using the Monte Carlo-based 3D radiobiological dosimetry (3D-RD) software and determined its additional value for predicting RBM toxicity.
View Article and Find Full Text PDFPurpose: Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies (bsMAb) and a radiolabeled peptide reduces the radiation dose to normal tissues. Here we report the accuracy of an (111)In-labeled pretherapy test dose for personalized dosing of (177)Lu-labeled IMP288 following pretargeting with the anti-CEA × anti-hapten bsMAb, TF2, in patients with metastatic colorectal cancer (CRC).
Methods: In 20 patients bone marrow absorbed doses (BMD) and doses to the kidneys were predicted based on blood samples and scintigrams acquired after (111)In-IMP288 injection for individualized dosing of PRIT with (177)Lu-IMP288.
Unlabelled: The prospects for using pretargeted immuno-SPECT to monitor the response to pretargeted radioimmunotherapy were examined. In this study, a bispecific anticarcinoembryonic antigen (CEACAM5; CD66e) × antihapten monoclonal antibody, TF2, was used in combination with a small (1.5 kD) peptide, IMP288, labeled with (111)In and (177)Lu.
View Article and Find Full Text PDFBackground: In this study, pretargeted immuno-positron-emission tomography [PET] with a bispecific monoclonal anti-carcinoembryonic antigen [CEA] (CEACAM5) × anti-hapten antibody (bispecific monoclonal antibody [bsmAb]) and a small (1.5 kD) peptide labeled with 68Ga was compared to fludeoxyglucose [18F-FDG]-PET for detecting intraperitoneal [i.p.
View Article and Find Full Text PDFUnlabelled: Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies in combination with a radiolabeled peptide reduces the radiation dose to normal tissues, especially the bone marrow. In this study, the optimization, therapeutic efficacy, and toxicity of PRIT of colon cancer with a (177)Lu-labeled peptide was determined in mice with carcinoembryonic antigen (CEA)-expressing human tumors.
Methods: To obtain the optimal therapeutic efficacy, several strategies were evaluated to increase the total amount of radioactivity targeted to subcutaneous LS174T colon cancer tumors in BALB/c nude mice.
(18)F-Fluorodeoxyglucose ((18)F-FDG) is the most common molecular imaging agent in oncology, with a high sensitivity and specificity for detecting several cancers. Antibodies could enhance specificity; therefore, procedures were developed for radiolabeling a small ( approximately 1451 Da) hapten peptide with (68)Ga or (18)F to compare their specificity with (18)F-FDG for detecting tumors using a pretargeting procedure. Mice were implanted with carcinoembryonic antigen (CEA; CEACAM5)-expressing LS174T human colonic tumors and a CEA-negative tumor, or an inflammation was induced in thigh muscle.
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