caa a22 4500 465786316 CHVBK 20180323112010.0 cr unu---uuuuu 170327e19900801xx s 000 0 eng 10.1007/BF00998159 doi (NATIONALLICENCE)springer-10.1007/BF00998159 Biodistribution in normal mice of an111in-labelled prostatic acid phosphatase-specific antibody and its F(ab′)2 fragments derivatized site-specifically or via bicyclic diethyl enetriaminepentaacetic acid anhydride [Elektronische Daten] [Maritta Perälä, Pirkko Vihko, Marja Södervall, Juhani Heikkilä, Reijo Vihko] In this study we examined optimization of derivatization of monoclonal antibodies and their fragments intended for use as radiopharmaceutical in radioimaging and/or radioimmunotherapy of prostatic cancer. Two different principles were used to conjugate diethylene triaminepentaacetic acid (DTPA) to a monoclonal antibody (Mab, subclass IgG1) raised against human prostatic acid phosphatase (PAP). In addition, the F(ab′)2 fragments of this Mab were also derivatized. We used the cyclic anhydride of DTPA (CA-DTPA) as a chelating agent for these two protein moieties. Furthermore, the Mab and the F(ab′)2 fragments were modified site-specifically by attaching linkers,N-(p-aminobenzyl)diethylenetriaminetetraacetic acid (p-NH2-Bz-DTTA) and 1(p-aminobenzyl)diethylenetriaminepentaacetic acid (p-NH2-Bz-DTPA), to the carbohydrate components of the parent molecules. In this study, biodistribution of the111In-labelled derivatives was investigated in normal mice. All the derivatives of IgG1 demonstrated a slower blood clearance than the corresponding derivatives of the F(ab′)2 fragments. This property was particularly pronounced in the site-specifically conjugated derivatives of IgG1. All the derivatives studied accumulated in the liver, kidney, and spleen. The CA-DTPA derivatives of F(ab′)2 fragments showed the highest kidney-to-blood ratios of radioactivity compared with the other compounds studied. The derivatives of IgG1 showed a higher percentage of the injected dose in liver and spleen tissues than the derivatives of the F(ab′)2 fragments. The F(ab′)2 fragments studied also gave rise to site-specific derivatives, which demonstrated that carbohydrates were also present in this part of the molecule. They behaved similarly to the CA-DTPA F(ab′)2 derivative in other respects, but the kidney accumulation was lower at 72 and 120 h. The F(ab′)2 fragments studied would be better suited for radioimaging than the derivatives of the IgG1 studied due to the rapid blood clearance of the F(ab′)2 derivatives. In contrast, the derivatives of IgG1, especially thep-NH2-Bz-DTPA conjugate, which showed the lowest kidney uptake, might be more suitable candidates for the development of therapeutic agents. Springer-Verlag, 1990 Radioimaging nationallicence Radiotherapy nationallicence Conjugation of antibodies nationallicence Perälä Maritta Biocenter and Department of Clinical Chemistry, University of Oulu, SF-90220, Oulu, Finland aut Vihko Pirkko Biocenter and Department of Clinical Chemistry, University of Oulu, SF-90220, Oulu, Finland aut Södervall Marja Research Center of Farmos Group Ltd, SF-20101, Box 425, Turku, Finland aut Heikkilä Juhani Biocenter and Department of Clinical Chemistry, University of Oulu, SF-90220, Oulu, Finland aut Vihko Reijo Biocenter and Department of Clinical Chemistry, University of Oulu, SF-90220, Oulu, Finland aut European Journal of Nuclear Medicine Springer-Verlag 16/8-10(1990-08-01), 621-626 0340-6997 16:8-10<621 1990 16 259 https://doi.org/10.1007/BF00998159 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00998159 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Perälä Maritta Biocenter and Department of Clinical Chemistry, University of Oulu, SF-90220, Oulu, Finland aut NATIONALLICENCE 700 1- Vihko Pirkko Biocenter and Department of Clinical Chemistry, University of Oulu, SF-90220, Oulu, Finland aut NATIONALLICENCE 700 1- Södervall Marja Research Center of Farmos Group Ltd, SF-20101, Box 425, Turku, Finland aut NATIONALLICENCE 700 1- Heikkilä Juhani Biocenter and Department of Clinical Chemistry, University of Oulu, SF-90220, Oulu, Finland aut NATIONALLICENCE 700 1- Vihko Reijo Biocenter and Department of Clinical Chemistry, University of Oulu, SF-90220, Oulu, Finland aut NATIONALLICENCE 773 0- European Journal of Nuclear Medicine Springer-Verlag 16/8-10(1990-08-01), 621-626 0340-6997 16:8-10<621 1990 16 259 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer