Kit For the Prepartion of Technetium Tc99m Sulfur Colloid

KIT FOR THE PREPARTION OF TECHNETIUM TC99M SULFUR COLLOID- technetium tc 99m sulfur colloid
Sun Pharmaceutical Industries, Inc.

1 INDICATIONS AND USAGE

Technetium Tc 99m Sulfur Colloid Injection is indicated:

In adults, to assist in the:

•

localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter.

•

evaluation of peritoneo-venous (LeVeen) shunt patency.

In adults and pediatric patients, for imaging:

•

areas of functioning reticuloendothelial cells in the liver, spleen and bone marrow.

•

studies of esophageal transit and, gastroesophageal reflux, and detection of pulmonary aspiration of gastric contents.

2 DOSAGE AND ADMINISTRATION

Technetium Tc 99m Sulfur Colloid Injection emits radiation. Use procedures to minimize radiation exposure. Measure patient dose by a suitable radioactivity calibration system immediately before administration.

2.1 Recommended Doses

•

Breast cancer or malignant melanoma setting in adults: 3.7 to 37 MBq (0.1 to 1 mCi) in volumes ranging from 0.1 to 1 mL by subcutaneous injection.

•

Peritoneo-venous (LeVeen) shunt setting in adults: 37 to 111 MBq (1 to 3 mCi) by intraperitoneal injection, or 12 to 37 MBq (0.3 to 1 mCi) in a volume not to exceed 0.5 mL by percutaneous transtubal (efferent limb) injection. Patient repositioning or other measures may be used to help assure uniform mixing of the radiopharmaceutical with peritoneal fluid.

•

Imaging areas of functioning reticuloendothelial cells:

In adults:

1.

liver/spleen imaging: 37 to 296 MBq (1 to 8 mCi) by intravenous injection;

2.

bone marrow imaging: 111 to 444 MBq (3 to 12 mCi) by intravenous injection.

In pediatric patients:

3.

liver/spleen imaging in children: 0.56 to 2.78 MBq (0.015 to 0.075 mCi) per kg of body weight (BW) by intravenous injection;

4.

liver/spleen imaging in newborns: 7.4 to 18.5 MBq (0.20 to 0.50 mCi) by intravenous injection;

5.

bone marrow imaging: 1.11 to 5.55 MBq (0.03 to 0.15 mCi) per kg of BW by intravenous injection.

•

Gastroesophageal and pulmonary aspiration imaging studies:

In adults:

6.

gastroesophageal studies: 5.55 to 11.1 MBq (0.15 to 0.30 mCi) by oral administration;

7.

pulmonary aspiration studies: 11.1 to 18.5 MBq (0.30 to 0.50 mCi) by oral administration.

In pediatric patients:

8.

gastroesophageal and pulmonary aspiration studies: 3.7 to 11.1 MBq (0.10 to 0.30 mCi) by oral or nasogastric tube administration. For oral administration, combine the radiopharmaceutical with a milk feeding. For nasogastric tube administration, administer the radiopharmaceutical into the stomach then instill a normal volume of dextrose or milk feeding.

2.2 Drug Preparation and Administration

•

The contents of the two Solution vials, the Solution A vial containing the appropriate acidic solution and the Solution B vial containing the appropriate buffer solution, are intended only for use in the preparation of the Technetium Tc 99m Sulfur Colloid Injection and are not to be directly administered to the patient.

•

Do not use Sodium Pertechnetate Tc 99m containing oxidants to reconstitute this kit.

•

The contents of the kit are not radioactive. However, after the Sodium Pertechnetate Tc 99m is added, maintain adequate shielding of the final preparation. Wear waterproof gloves during the preparation procedure.

•

Do not use Sodium Pertechnetate Tc 99m containing more than 10 micrograms per mL of aluminum ion because a flocculent precipitate may occur and such a precipitate may localize in the lung.

•

The contents of the kit are sterile and non-pyrogenic. This preparation contains no bacteriostatic preservative. Follow the directions carefully and adhere strictly to aseptic procedures during preparation.

Prepare Technetium Tc 99m Sulfur Colloid Injection by the following aseptic procedure:

1.

Remove the dark brown plastic cap from the Sulfur Colloid multi-dose Reaction Vial and swab the top of the vial closure with alcohol to sterilize the surface. Complete the radiation label and affix to the vial. Place the vial in an appropriate lead-capped radiation shield labeled and identified.

2.

With a sterile shielded syringe, aseptically obtain 1 to 3 mL of a suitable, oxidant-free sterile and non-pyrogenic Sodium Pertechnetate Tc 99m, each milliliter containing a maximum activity of 18,500 MBq (500 mCi).

3.

Aseptically add the Sodium Pertechnetate Tc 99m to the vial.

4.

Place a lead cover on the vial shield and dissolve the reagent by gentle swirling.

5.

Just before use, remove the red cap from the Solution A vial and swab the top of the vial closure with alcohol to sterilize the surface. Using a sterile needle and syringe, aseptically withdraw 1.5 mL Solution A from the vial. Aseptically Inject 1.5mL Solution A into the multi-dose Reaction Vial and swirl again.

6.

Transfer the multi-dose Reaction Vial from vial shield and place in a vigorously boiling water bath (water bath should be shielded with 1/8” to 1/4” lead) deep enough to cover the entire liquid contents of the vial. Keep the vial in the water bath for five minutes.

7.

Remove the multi-dose Reaction Vial from the water bath and place in the lead shield and allow to cool for three minutes. Swab the vial closure again with an antiseptic.

8.

Just before use, remove the blue cap from the Solution B vial and swab the top of the vial closure with alcohol to sterilize the surface. Using a sterile needle and syringe, aseptically withdraw 1.5 mL Solution B from the vial. Aseptically Inject 1.5 mL Solution B into the multi-dose Reaction Vial and swirl again.

9.

Record time and date of preparation.

10.

Allow the preparation to cool to body temperature before use. Maintain adequate shielding of the radioactive colloid preparation at all times.

11.

Where appropriate, dilute the preparation with sterile Sodium Chloride Injection to bring the dosage to within the recommended range.

12.

Mix the multi-dose Reaction Vial and aseptically withdraw material with a sterile shielded syringe for use within 6 hours of preparation. For optimum results this time should be minimized. The vial contains no bacteriostatic preservative. Store the reconstituted vial at 20 to 25°C (68 to77°F). Discard vial 6 hours after reconstitution.

13.

Carefully agitate the shielded syringe immediately prior to administration of sulfur colloid to avoid particles aggregation and non-uniform distribution of radioactivity.

Measure the patient dose by a suitable radioactivity calibration system immediately before administration. Check radiochemical purity before patient administration.

Inspect Technetium Tc 99m Sulfur Colloid Injection visually for particulate matter and discoloration before administration, whenever solution and container permit. Do not administer the drug if it contains particulate matter or discoloration; dispose of these unacceptable or unused preparations in a safe manner, in compliance with applicable regulations.

2.3 Radiation Dosimetry

•

Subcutaneous injection to assist in lymph node localization

Table 1. Estimated Adult Absorbed Radiation Doses from Subcutaneous Administration of Technetium Tc 99m Sulfur Colloid Injection (mSv/MBq and rem/mCi)¹

Target Organ	mSv/MBq	rem/mCi
Injection Site	9.51	35. 2
Lymph Nodes	0.951	3.52
Liver	0.0028	0.0104
Spleen	0.0017	0.00629
Bone Marrow	0.0019	0.00703
Testes	0.0009	0.0033
Ovaries	0.00018	0.00066
Total Body	0.004	0.0148

¹ Bergqvist L, Strand S-E, Persson B, et al. Dosimetry in
Lymphoscintigraphy of Tc 99m Antimony Sulfide Colloid,
J Nucl Med, 23: 698-705, 1982.

•

Intravenous Injection

Adult Radiation Doses

Table 2. Estimated Adult Absorbed Radiation Doses from Technetium Tc 99m Sulfur Colloid Injection Administration (mSv/MBq and rem/mCi)²

			Diffuse Parenchymal Disease
Target Organ	Normal Liver		Early to Intermediate		Intermediate to Advanced
	mSv/MBq	rem/mCi	mSv/MBq	rem/mCi	mSv/MBq	rem/mCi
Liver	0.091	0.338	0.058	0.213	0.044	0.163
Spleen	0.058	0.213	0.074	0.275	0.115	0.425
Bone Marrow	0.008	0.028	0.012	0.045	0.021	0.079
Testes	0.0003	0.001	0.0005	0.002	0.0008	0.003
Ovaries	0.0016	0.006	0.0022	0.008	0.0032	0.012
Total Body	0.005	0.019	0.005	0.019	0.005	0.018

² Modified from Summary of Current Radiation Dose Estimates to Humans with Various Liver Conditions from 99m Tc-Sulfur Colloid, MIRD Dose Estimate Report No 3, J Nucl Med 16: 108A — 108B, 197

Pediatric Radiation Doses

Table 3A. Estimated Pediatric Absorbed Radiation Doses from Technetium Tc 99m Sulfur Colloid Injection Administration of 1 MBq and 1 mCi for Liver/Spleen and Bone Marrow Imaging (in mSv/MBq and rem/mCi)³

Age Body Weight		Newborn 3.5 kg	1 year 12.1 kg	5 years 20.3 kg	10 years 33.5 kg	15 years 55 kg
Absorbed Dose
Target Organ
Liver	mSv/MBq	0.86	0.38	0.22	0.18	0.13
	rem/mCi	3.2	1.4	0.82	0.67	0.49
Spleen	mSv/MBq	0.76	0.32	0.18	0.13	0.09
	rem/mCi	2.8	1.2	0.65	0.49	0.33
Red Marrow	mSv/MBq	0.16	0.05	0.03	0.022	0.01
	rem/mCi	0.58	0.18	0.11	0.081	0.036
Ovaries	mSv/MBq	0.04	0.02	0.0103	0.0043	0.0022
	rem/mCi	0.14	0.064	0.038	0.016	0.008
Testes	mSv/MBq	0.011	0.006	0.004	0.004	0.001
	rem/mCi	0.04	0.021	0.013	0.014	0.002
Total Body	mSv/MBq	0.032	0.026	0.018	0.012	0.006
	rem/mCi	0.12	0.096	0.066	0.043	0.022

³ from Age-dependent “S” values of Henrichs et al, Berlin 1982, except for the 1-year old.
The 1-year old “S” values were taken from phantom work of the Metabolism and Dosimetry Group at ORNL

Table 3B. Estimated Pediatric Maximum Absorbed Radiation Doses from Administration of the Maximum Recommended Dose for Technetium Tc 99m Sulfur Colloid Injection (mSv and rem) ³

Age Body Weight		Newborn 3.5 kg		1 year 12.1 kg		5 years 20.3 kg		10 years 33.5 kg		15 years 55 kg
Maximum Recommended Dose:		a*	b*	a*	b*	a*	b*	a*	b*	a*	b*
MBq		18.5	22.2	33.3	67.3	55.5	114.7	92.5	186.1	151.7	307.1
mCi		0.5	0.6	0.9	1.82	1.5	3.1	2.5	5.03	4.1	8.3
Maximum Absorbed Dose from Maximum Recommended Dose Administered (mSv and rem)
Target Organ
Liver	mSv	16	19.2	12.6	25.46	12.3	25.42	16.7	33.6	20.1	40.69
	rem	1.6	1.92	1.26	2.55	1.23	2.54	1.67	3.36	2.01	4.07
Spleen	mSv	14	16.8	10.8	21.83	9.75	20.15	12.2	24.55	13.5	27.33
	rem	1.4	1.68	1.08	2.18	0.98	2.02	1.22	2.45	1.35	2.73
Red Marrow	mSv	2.9	3.48	1.62	3.27	1.65	3.41	2.03	4.08	1.48	3
	rem	0.29	0.35	0.16	0.33	0.17	0.34	0.2	0.41	0.15	0.3
Ovaries	mSv	0.7	0.84	0.58	1.17	0.57	1.18	0.4	0.8	0.34	0.69
	rem	0.07	0.084	0.058	0.117	0.057	0.118	0.04	0.08	0.034	0.069
Testes	mSv	0.2	0.24	0.19	0.38	0.2	0.41	0.35	0.7	0.09	0.18
	rem	0.02	0.024	0.019	0.038	0.02	0.041	0.035	0.07	0.009	0.018
Total Body	mSv	0.6	0.72	0.86	1.74	0.99	2.05	1.07	2.15	0.9	1.82
	rem	0.06	0.072	0.086	0.174	0.099	0.205	0.107	0.215	0.09	0.182

^*a liver/spleen imaging

^*b bone marrow imaging

³ from Age-dependent “S” values of Henrichs et al., Berlin 1982, except for the 1-year old.
The 1-year old “S” values were taken from phantom work of the Metabolism and Dosimetry Group at ORNL

•

Oral Administration

Table 4. Adult Radiation Absorbed Dose from Oral Administration of 1mCi of Technetium Tc99m Sulfur Colloid Injection (mSv/MBq and rem/mCi)

Target Organ	Assumed Residence Time (hr.)	mSv/MBq	rem/mCi
Stomach Wall	1.5	0.038	0.14
Small Intestine	4	0.07	0.26
Upper Large Intestine Wall	13	0.13	0.48
Upper Large Intestine Wall	24	0.089	0.33
Ovaries	–	0.026	0.096
Testes	–	0.001	0.005
Total Body	–	0.005	0.018

•

Intraperitoneal Injection

Table 5. Adult Absorbed Radiation Dose from Intraperitoneal Injection of 3 mCi of Technetium Tc 99m Sulfur Colloid (mSv/MBq and rem/mCi)

Target Organ	Shunt Open		Shunt Closed
	mSv/MBq	rem/mCi	mSv/MBq	rem/mCi
Liver	0.092	0.34	0.015	0.056
Ovaries and Testes	0.0003 to 0.0016	0.0012 to 0.006	0.015	0.056
Organs in the Peritoneal Cavity	–	–	0.015	0.056
Total Body	0.0049	0.0180	0.005	0.019

Assumptions: Calculations for the absorbed radiation dose are based upon an effective half-time of 3 hours for the open shunt and 6.02 hours for the closed shunt and an even distribution of the radiopharmaceutical in the peritoneal cavity with no biological clearance.

•

Other Exposure Estimates

Table 6. Radiation Doses to Hospital Personnel (µSv/MBq and mrem/mCi)

Technician	Preparation of Drug*		Administered Drug
Target	µSv/MBq	mrem/mCi	µSv/MBq	mrem/mCi
Extremity Dose	0.016	0.0575	0.07	0.25
Whole Body Dose	0.0007	0.0025	0.003	0.0125

*Using shielded vial and syringe