title: Pharmacokinetics and dosimetry of [111In] F(ab')2 fragments against prostatic acid phosphatase after intraprostatic injection for immunoscintigraphy in prostate cancer.
abstract: The purpose of this study was to investigate the pharmacokinetics and dosimetry of using [111In]-labelled F(ab')2 fragments against prostate acid phosphatase (FC-3001, Orion Corporation Farmos, Finland) for the detection of metastatic prostate cancer. Five patients in all were subjected to intraprostatic injection of 1 mg FC-3001 labelled with 85-100 MBq [111In]. In four of the patients the biodistribution was studied by sequential whole-body counting, gamma-camera scintigraphy of the abdomen in antero-posterior and postero-anterior projections. Blood and urine samples were collected sequentially up to 72 h after injection. Initially, significant amounts of antibody fragments were released from the site of injection. After the first 4 h, 22.0% of injected antibody (2.2-41.3% ID) remained in the prostate and was slowly released with a final half-life of 80.4 h (49.9-141.8 h). Labelled antibody appeared in the blood shortly after injection and was cleared from the blood with a final half-life of 27.7-300.9 h. The liver, the bone marrow and, in two patients, the kidneys accumulated antibody fragments in significant amounts during the period of investigation. An apparent relationship between the initial whole-body clearance and renal uptake is described. The effective dose averaged 0.37 mSv/MBq (range 0.24-0.52 mSv/MBq). The highest equivalent doses were received by the kidneys (0.46-2.81 mGy/MBq) the liver (0.44-1.59 mGy/MBq) and the bone marrow (0.37-0.57 mGy/MBq). Only in two of the patients with known metastases were pathological foci seen. The disappointing imaging results were probably caused by the biphasic release of antibody from the prostate, and indicates that intraprostatic injection of this antibody has no advantage for imaging, as well as being unpleasant for the patient. The biodistribution of the antibody following release from the prostate is similar to but more variable than the biodistribution seen in patients after intravenous injection of labelled antibodies.
authors.affiliation: Dept of Clinical Physiology and Nuclear Medicine, Aarhus University Hospital, Denmark.
authors.forename: J T
authors.initials: JT
authors.lastname: Nielsen
authors.forename: J
authors.initials: J
authors.lastname: Poulsen
authors.forename: C
authors.initials: C
authors.lastname: Flø
authors.forename: J
authors.initials: J
authors.lastname: Marqversen
authors.forename: M
authors.initials: M
authors.lastname: Rehling
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal; D006801:Humans; D007205:Indium Radioisotopes; D008297:Male; D008875:Middle Aged; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology*; D011467:Prostate / Q000276:immunology; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology; D011863:Radioimmunoassay; D011869:Radioligand Assay; D011877:Radionuclide Imaging
chemical_list: D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D010744:Phosphoric Monoester Hydrolases