Indium In 111 oxyquinoline (oxine) is a diagnostic radiopharmaceutical intended for
radiolabeling autologous leukocytes. It is supplied as a sterile, non-pyrogenic, isotonic aqueous
solution with a pH range of 6.5 to 7.5. Each mL of the solution contains 37 MBq, 1 mCi of
indium In 111 [no carrier added, >1.85 GBq/µg indium (>50 mCi/µg indium)] at calibration
time, 50 µg oxyquinoline, 100 µg polysorbate 80, and 6 mg of HEPES (N-2-hydroxyethyl-
piperazine-N'-2-ethane sulfonic acid) buffer in 0.75% sodium chloride solution. The drug is
intended for single use only and contains no bacteriostatic agent. The radionuclidic impurity
limit for indium 114m is not greater than 37 kBq, 1 µCi of indium 114m per 37 MBq, 1 mCi of
indium In 111 at the time of calibration. The radionuclidic composition at expiration time is not
less than 99.75% of indium In 111 and not more than 0.25% of indium In 114m/114.
Chemical name: Indium In 111 Oxyquinoline.
The precise structure of the indium In 111 oxyquinoline complex is unknown at this time. The
empirical formula is (C
Indium In 111 decays by electron capture with a physical half-life of 67.2 hours (2.8 days). The
energies of the photons that are useful for detection and imaging studies are listed in Table 1.
Table 1. Principal Radiation Emission Data
Kocher, David C., "Radioactive Decay Data Tables", DOE/TIC-11026, 115 (1981).
The exposure rate constant for 37 MBq, 1 mCi indium In 111 is 8.3 × 10
C/kg/h (3.21 R/h) at 1
for the relative attenuation of the radiation emitted by this radionuclide that results from the
interposition of various thicknesses of Pb is shown in Table 2. For example, the use of 0.834 cm
of lead will decrease the external radiation exposure by a factor of about 1,000.
Data supplied by Oak Ridge Associated Universities, Radiopharmaceutical Internal Dose Information
These estimates of attenuation do not take into consideration the presence of longer-lived
To allow correction for physical decay of indium In 111, the fractions that remain at selected
Table 3. Physical Decay Chart for Indium In 111,
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
approximately 3-4 × 10
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
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
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
feces and urine in 24 hours.
Clearance from whole blood and biological distribution can vary considerably with the
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).
INDICATIONS AND USAGE
Indium In 111 oxyquinoline is indicated for radiolabeling autologous leukocytes.
Indium In 111 oxyquinoline labeled leukocytes may be used as an adjunct in the detection of
other infection, following reinjection and detection by appropriate imaging procedures. The
degree of accuracy may vary with labeling techniques and with the size, location and nature of
the inflammatory process.
Indium In 111 oxyquinoline labeled leukocyte imaging is not the preferred technique for the
Ultrasound or computed tomography may provide a better anatomical delineation of the
infectious process and information may be obtained more quickly than with labeled leukocytes.
If localization by these techniques is successful, labeled leukocytes should not be used as a
confirmatory procedure. If localization or diagnosis by these methods fails or is ambiguous,
indium In 111 oxyquinoline labeled leukocyte imaging may be appropriate.
The content of the vial of indium In 111 oxyquinoline solution is intended only for use in the
preparation of indium In 111 oxyquinoline labeled autologous leukocytes, and is not to be
administered directly. Autologous leukocyte labeling is not recommended in leukopenic patients
because of the small number of available leukocytes.
Due to radiation exposure, indium In 111 oxyquinoline labeled leukocytes could cause fetal harm
patient should be informed of the potential hazard to the fetus.
Indium In 111 oxyquinoline labeled autologous leukocytes should be used only when the benefit
high radiation burden and the potential for delayed manifestation of long-term adverse effects.
Clumping of cells may produce focal accumulations of radioactivity in lungs which do not wash
out in 24 hours and thus may lead to false positive results. This phenomenon can be detected by
imaging the chest immediately after injection.
The normally high uptake of indium In 111 oxyquinoline labeled leukocytes by spleen and liver
accumulate in the colon and accessory spleens of patients with or without disease.
Chemotaxis of granulocytes deteriorates during storage and loss of chemotaxis may cause false
3% at one hour to 24% at 24 hours [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)]. The maximum amount of time recommended between drawing
the blood and reinjection should not exceed 5 hours. It is recommended that the labeled cells be
used within one hour of preparation, if possible and in no case more than three hours after
Plasma and red cell contamination impairs labeling efficiency of leukocytes. Hemolyzed blood
Cell aggregates of various degrees have been reported. Cell labeling techniques and standing of
Nuclear medicine procedures involving withdrawal and reinjection of blood have the potential
administration errors and viral contamination of personnel during blood product labeling. A
system of checks similar to the ones used for administering blood transfusions should be routine.
Strict aseptic techniques should be used to maintain sterility throughout the procedures for using
Do not use after the expiration time and date (5 days after calibration time) stated on the label.
The contents of the vial are radioactive. Adequate shielding of the preparation must be
maintained at all times.
Indium In 111 oxyquinoline, like other radioactive drugs, must be handled with care and
Care should also be taken to minimize radiation exposure to the patient consistent with proper
Radiopharmaceuticals should be used only by physicians who are qualified by training and
been approved by the appropriate governmental agency authorized to license the use of radio-
Carcinogenesis, Mutagenesis, Impairment of Fertility
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
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/10
, 15 µCi/10
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 10
leukocytes is 9 × 10
mGy (0.9 × 10
rads) from 18.5 MBq, 500 µCi [Goodwin, David A., Cell labeling with oxine chelates of
Studies have not been performed to evaluate whether indium In 111 oxyquinoline affects fertility
Pregnancy Category C
Animal reproduction studies have not been conducted with Indium In 111 Oxyquinoline labeled
leukocytes. It is also not known whether Indium In 111 Oxyquinoline labeled leukocytes can
cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
However, Indium Nitrate, a closely related compound, was teratogenic and embryopathic in
hamsters. Indium In 111 Oxyquinoline labeled leukocytes should be given to a pregnant woman
only if clearly needed.
of childbearing capability should be performed during the first few (approximately ten) days
following the onset of menses.
It is reported that indium 111 is secreted in human milk following administration of indium In
111 labeled leukocytes. Therefore, formula feedings should be substituted for breast feedings.
Safety and effectiveness in pediatric patients below age 18 have not been established (See
Other reported clinical experience has not identified differences in responses between the elderly
and younger patients. In general, dose selection for an elderly patient should be cautious usually
starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic,
renal, or cardiac function, and of concomitant disease or other drug therapy.
Sensitivity reactions (urticaria) have been reported. The presence of fever may mask pyrogenic
reactions from indium In 111 oxyquinoline labeled leukocytes. The possibility of delayed
adverse reactions has not been studied.
DOSAGE AND ADMINISTRATION
The recommended adult (70 kg) dose of indium In 111 oxyquinoline labeled autologous
leukocytes is 7.4 to 18.5 MBq, 200-500 µCi. Indium In 111 oxyquinoline solution is intended for
the radiolabeling of autologous leukocytes. The indium In 111 oxyquinoline labeled autologous
leukocytes are administered intravenously.
Imaging is recommended at approximately 24 hours post injection. Typically, anterior and
Aseptic procedures and a shielded syringe should be employed in the withdrawal of indium In
procedure and the administration of the labeled leukocytes to the patient. The user should wear
waterproof gloves during the entire procedure. The patient's dose should be measured by a
suitable radioactivity calibration system immediately before administration. At this time, the
leukocyte preparation should be checked for gross clumping and red blood cell contamination.
The estimated absorbed radiation doses to an adult patient weighing 70 kg from an intravenous
dose of 18.5 MBq, 500 µCi of indium In 111 oxyquinoline labeled leukocytes including
contributions from indium In 114m/114 as a radionuclidic impurity are shown in Table 4.
Assumptions: 30% to spleen, 30% to liver, 34% to red marrow, 6% to remainder of body, with
The dose of radiation absorbed by the organs will vary with the distribution of the blood cells in
Sterile technique must be used throughout. It is important that all equipment used for the
preparation of reagents be thoroughly cleaned to assure the absence of trace metal impurities.
The user should wear waterproof gloves during the handling and administration procedure.
1. The following equipment is recommended:
gauge needle (NOTE: Do not use a smaller gauge needle).
Ring stand and clamp(s).
Three (3) 50 mL sterile conical plastic centrifuge tubes with screw caps. Label each set
with patient ID and "WBC", "LPP" and "Wash" respectively (NOTE: 3 centrifuge tubes
Clinical Centrifuge with horizontal, 4 place rotor or equivalent.
Sodium Chloride 0.9% Injection, USP.
Three (3) disposable 5 or 10 mL syringes and 19 gauge needles.
Syringe shield to dispense indium In 111 oxyquinoline.
A dose calibrator.
Butterfly catheter infusion set.
Test tube rack.
10 mL syringe with a 19 gauge or 20 gauge needle.
19 gauge needle with filter (optional).
2. Withdraw from the patient 30-50 mL blood [preferably fifty (50) mL] using aseptic
venipuncture technique using the 60 mL syringe fitted with a 19 gauge or 20 gauge
needle and containing approximately 1000-1500 units heparin in 1-2 mL. Blood
withdrawal should be smooth and slow so as not to produce bubbles or foaming.
3. Remove and dispose of the needle and replace with a syringe cap. Gently mix the
contents of the syringe and label with the patient's ID, date and time.
4. Upon receipt of the full syringe for processing, the contents should again be gently
the syringe 10-20 degrees from its position perpendicular to the bench.
6. Allow the red cells to sediment 30-60 minutes, depending upon when the supernatant
[leukocyte rich plasma (LRP)] looks clear of red blood cells.
7. Replace the syringe cap with an infusion set.
8. Collect the plasma (LRP) in the centrifuge tube marked "WBC" by expressing the LRP
through the catheter tubing making sure not to get any red cells into the WBC tube.
9. Immediately centrifuge the capped WBC tube at 400-450 g for 5 minutes.
mL supernatant to cover the white cell button (NOTE: the button often contains a small
number of red cells and may appear red).
11. Wash the white cell button with 4-6 mL Sodium Chloride (0.9%) Injection, USP.
Resuspend the button by gentle swirling.
12. Centrifuge the capped WBC tube at 400-450 g for 5 minutes (alternatively, 150 g for 8
minutes) and discard all but 0.5-1.0 mL of the supernate to cover the cells.
13. Add 5.0 mL Sodium Chloride (0.9%) Injection, USP. Resuspend the cells by gentle
14. With the shielded syringe, draw up approximately 22.2 MBq, 600 µCi indium In 111
oxyquinoline. Check the amount of radioactivity in a dose calibrator set for indium In
111 and record for labeling efficiency calculations.
Parenteral drug products should be inspected visually for particulate matter and
15. In several additions, add the indium In 111 oxyquinoline to the WBC tube, gently
swirling after each addition.
16. Set the lab timer for 15 minutes and allow the capped WBC tube to incubate. Swirl the
cell preparation several times during the incubation.
17. With a sterile plastic syringe, add half of the saved LPP (or about 8 mL) from the LPP
tube. Cap and gently swirl the contents of WBC tube to resuspend the cells.
18. Centrifuge the WBC tube at 450 g for 5 minutes (or 150 g for 8 minutes). Decant
supernatant into the wash tube leaving behind about 0.5 mL of the supernate to cover the
20. With a sterile plastic syringe add the remaining LPP to the cell button and gently
resuspend by swirling. With a sterile syringe fitted with a 19 gauge needle, resuspend
the cells by drawing the cells up into the syringe and expressing the suspension against
the tube gently once or twice. Alternatively, draw up the cells into a syringe fitted with
the filtered 19 gauge needle, and replace the needle with an unfiltered 19 or 20 gauge
21. Reserve in the WBC tube a minimum amount of white cell suspension for a WBC count.
A microscopic examination should also be completed to observe for clumping. Draw up
the patient's dose (7.4 to 18.5 MBq, 200-500 µCi) and check the syringe in the dose
calibrator. Record the measurement.
It is generally advantageous to record any observations on cell abnormalities (e.g., cell
clumping). A trypan blue exclusion test may also be performed.
It is recommended that the preparation be used within one hour of labeling (See Precautions).
Indium In 111 oxyquinoline solution is supplied in a vial as a single use only product containing
37 MBq, 1.0 mCi in 1.0 mL aqueous solution at the calibration date stated on the label. Vials are
packaged in individual lead shields.
The contents of the vial are radioactive and adequate shielding and handling precautions must be
This preparation is approved for use by persons licensed by the Illinois Emergency Management
the Nuclear Regulatory Commission or an Agreement State.
SPECIAL HANDLING AND STORAGE
Indium In 111 oxyquinoline solution should be stored at room temperature (15-25°C, 59-77°F).
Indium In 111 oxyquinoline labeled autologous leukocytes should preferably be reinjected
77°F) for up to three hours following completion of the cell labeling procedure. Reinjection of
indium In 111 oxyquinoline labeled autologous leukocytes more than 5 hours after initial blood
drawing is not recommended.
Sterile technique must be used throughout the collection, labeling and re-injection procedures.
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