Source: FDA, National Drug Code (US) Revision Year: 2021
Indium forms a saturated (1:3) complex with oxyquinoline. The complex is neutral and lipid-soluble, which enables it to penetrate the cell membrane. Within the cell, indium becomes firmly attached to cytoplasmic components; the liberated oxyquinoline is released by the cell. It is thought likely that the mechanism of labeling cells with indium In-111 oxyquinoline involves an exchange reaction between the oxyquinoline carrier and subcellular components which chelate indium more strongly than oxyquinoline. The low stability constant of the oxyquinoline complex, estimated at approximately 10, supports this theory.
Following the recommended leukocyte cell labeling procedure, approximately 77% of the added indium In-111 oxyquinoline is incorporated in the resulting cell pellet (which represents approximately 3-4 × 108 WBC).
Cell clumping can occur and was found in about one fifth of the leukocyte preparations examined. The presence of red blood cells or plasma will lead to reduced leukocyte labeling efficiency. Transferrin in plasma competes for indium In-111 oxyquinoline.
After injection of labeled leukocytes into normal volunteers, about 30% of the dose is taken up by spleen and 30% by liver, reaching a plateau at 2-48 hours after injection. No significant clearance of radioactivity is observed at 72 hours in these two organs. Pulmonary uptake is 4-7.5% at 10 minutes but is lost rapidly; pulmonary radioactivity is usually visible in scans only up to about 4 hours after injection.
The human biodistribution studies in three normal subjects injected with indium In-111 oxyquinoline labeled leukocytes indicate a biexponential disappearance of indium In-111 from the blood when monitored for up to 72 hours. Between 9.5 to 24.4% of the injected dose remains in whole blood and clears with a biological half-time of 2.8 to 5.5 hours. The remainder (13-18%) clears from blood with a biological half-time of 64 to 116 hours.
Elimination from the body of injected indium In-111 oxyquinoline is probably mainly through decay to stable cadmium since only a negligible amount (less than 1%) of the dose is excreted in feces and urine in 24 hours.
Clearance from whole blood and biological distribution can vary considerably with the individual recipient, the condition of the injected cells and labeling techniques used.
Release of radioactivity from the labeled cells is about 3% at 1 hour and 24% at 24 hours.
Clearance from liver and spleen, for the purpose of calculating the radiation dose, is assumed to be equal to the physical half-life of indium In-111 (67.2 hours).
Although earlier studies suggested that oxyquinoline (oxine) might have carcinogenic potential, recent studies have found no evidence of carcinogenicity in either rats or mice given oxyquinoline in feed at concentrations of 1,500 or 3,000 ppm for 103 weeks.
It has been reported [ten Berge, R.J.M., Natarajan, A.T., Hardeman, M.R., et al, Labeling with indium In-111 has detrimental effects on human lymphocytes, Journal of Nuclear Medicine, 24, 615-620 (1983)] that human lymphocytes labeled with recommended concentrations of indium In-111 oxyquinoline showed chromosome aberrations consisting of gaps, breaks and exchanges that appear to be radiation induced. At 555 kBq/107, 15 µCi/107 lymphocytes 93% of the cells were reported to be abnormal. The oncogenic potential of such lymphocytes has not been studied. It has been reported that the radiation dose to 108 leukocytes is 9 × 104 mGy (0.9 × 104 rads) from 18.5 MBq, 500 µCi [Goodwin, David A., Cell labeling with oxine chelates of radioactive metal ions: Techniques and clinical implications, Journal of Nuclear Medicine, 19, 557-559 (1978)].
Studies have not been performed to evaluate whether indium In-111 oxyquinoline affects fertility in male or female laboratory animals or humans.
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