TY - JOUR
AU - Hinkle, George, H.
AB - Abstract Purpose. The stability of a mixture of technetium Tc 99m sulfur colloid and lidocaine hydrochloride for up to eight hours was studied. Methods. Three vials of technetium Tc 99m sulfur colloid were compounded according to the manufacturer’s instructions. From each of the three vials, five samples were withdrawn into syringes with needles: 0.4, 0.45, 0.5, 0.63, and 1 mCi for testing after storage for zero, one, two, four, and eight hours, respectively. Each syringe contained the customary patient dose of 0.4 mCi at the time of testing. Fresh 0.9% sodium chloride injection was used to bring the volume of each syringe to 0.2 mL, and 0.2 mL of lidocaine hydrochloride 1% was added to bring the final volume to 0.4 mL. Measurements of pH, radiochemical purity, and particle size were conducted after the indicated storage times for each group of samples. Results. The pH of samples showed no substantial change over the eight-hour storage period, with individual values in the range of 4.5–5.5. Radiochemical purity did not change substantially, with values ranging from 98.9% to 99.9%. There was no meaningful change in the amount of radioactivity retained by filtration and no increase in particle size. Conclusion. Adding lidocaine hydrochloride 1% to syringes containing technetium Tc 99m sulfur colloid and storing the syringes for up to eight hours had no effect on the pH or radiochemical purity of the mixture or on the radioactivity retained by a filter. Anesthetics, local, Diluents, Hydrogen ion concentration, Incompatibilities, Injections, Lidocaine hydrochloride, Particle size, Purity, Radiopharmaceuticals, Sodium chloride, Stability, Storage, Technetium Tc 99m sulfur colloid Technetium Tc 99m sulfur colloid is a radiopharmaceutical used for imaging areas of functioning reticuloendothelial cells in the liver, spleen, and bone marrow; evaluating peritoneovenous shunt patency; and (when given orally) imaging the gastrointestinal system. Since its introduction, this radiopharmaceutical has also been used for lymphoscintigraphy, or imaging the lymphatic vessels and nodes draining a particular organ or disease site. Along with lymphoscintigraphy, sentinel lymph node identification has substantially aided in the staging and surgical management of skin cancers, breast cancers, and other solid tumors.1,–4 Although several radioactive compounds have been used for lymphoscintigraphy, lymphatic mapping, and sentinel lymph node biopsy, technetium Tc 99m sulfur colloid has been the drug of choice.5,–7 Because the subcutaneous, intradermal, or interstitial administration of technetium Tc 99m sulfur colloid typically causes discomfort or pain at the injection site, the local anesthetic lidocaine is sometimes used simultaneously.1,3,8,9 Some physicians prefer to anesthetize the injection area by injecting lidocaine locally before administering technetium Tc 99m sulfur colloid,10 whereas others prefer to coinject a mixture of lidocaine and technetium Tc 99m sulfur colloid.3 Although several investigators have reported on the stability of technetium Tc 99m sulfur colloid when used for clinical studies, there are no data evaluating the possible reduction in product purity over time when mixed with lidocaine.11,–14 The purpose of this study was to evaluate the stability of a mixture of technetium Tc 99m sulfur colloid and lidocaine hydrochloride for up to eight hours. Methods Preparation of technetium Tc 99m sulfur colloid Technetium Tc 99m sulfur colloid was prepared from sulfur colloid kits (CIS-Sulfur Colloid kita) according to the manufacturer’s instructions by using 100 mCi of technetium Tc 99m sodium pertechnetate (in 1 mL) from a radionuclide generator.15 Three separate vials were prepared on the same day. The resultant product contains particles of Tc 99m with a size range of 0.1–2 μm (average size range, 0.3–0.5 μm).11,16 Preparation of syringes containing simulated patient doses From each of the three vials of technetium Tc 99m sulfur colloid, five samples were taken: 0.4, 0.45, 0.5, 0.63, and 1 mCi for testing after storage for zero, one, two, four, and eight hours, respectively. The samples were withdrawn into 1-mL syringes with standard 27-gauge needles. Taking into account radioactive decay, each of these samples would yield 0.4 mCi, a simulated patient dose, at the time of testing. Fresh 0.9% sodium chloride injectionb was used to bring the volume in each syringe to 0.2 mL, and 0.2 mL of lidocaine hydrochloride 1%c was added to bring the final volume to 0.4 mL. The time was recorded for each group of five samples after the lidocaine was added. The syringes were stored in lead-lined containers at room temperature (20–23 °C). No lidocaine-free controls were used, since this is the form of technetium Tc 99m sulfur colloid dispensed normally and since the stability of this preparation under the conditions described is well documented.11,–14 Measurement of pH Nitrazine paper (pH detection range, 4.5–7.5) was used to determine the pH of the samples stored for zero, one, two, four, and eight hours. A small drop from each syringe was placed on one end of a 1-in strip of nitrazine paper held in front of a white background. Values were read from the plastic holder indicator immediately, while the paper was still wet. Determination of radiochemical purity Thin-layer chromatography (TLC)d with development in fresh 0.9% sodium chloride injection was used to determine the radiochemical purity of the samples.17,18 Each shielded unit dose syringe was inverted 10 times before sampling. A small drop (approximately 5 μL) from each syringe was placed on a 1 × 8 cm TLC strip at the origin, 2 cm from the end of the strip. The strip was placed in a glass tube containing fresh 0.9% sodium chloride injection as mobile-phase solvent. After the mobile phase was allowed to travel to the top of the strip, the strip was removed and cut in half, and the radioactivity in each half of the strip was determined with a well counting system. The percentage of total radioactivity in the lower half of the strip (containing the origin) provided a measurement of the radiochemical purity of the technetium Tc 99m sulfur colloid. Estimation of particle size Membrane filtration was used to evaluate particle size in the samples.11,19,20 Volumes of 0.1 mL from each stored syringe were passed through a 0.1-μm polycarbonate membrane filtere prewetted with sterile water for injection.f The filter was rinsed with 1 mL of sterile water for injection. The percentage of radioactivity retained by the filter was determined by counting the filter unit, and radioactivity was expressed as a percentage of the total radioactivity—a combination of the counts from the filter unit, filtrate, and washing. Results Simulated patient doses of technetium Tc 99m sulfur colloid mixed with lidocaine hydrochloride 1% and stored up to eight hours showed no substantial change in pH (Table 11); individual values were in the range of 4.5–5.5. All pH values were within the USP specification of 4.5–7.5.21 Chromatography revealed no substantial changes in radiochemical purity over the eight-hour period (Table 1 1). Individual radiochemical purity values ranged from 98.9% to 99.9%, exceeding the USP specification of 92%.21 Passage through a 0.1-μm polycarbonate filter led to a retention of a mean ± S.D. of 65.7% ± 2.5% of the radioactivity (n = 15). There was no substantial change in the amount of radioactivity retained by filtration and no suggestion of an increase in particle size. Table 1. Mean ± S.D. Radiochemical Purity, Particle Size, and pH of Mixture of Technetium Tc 99m Sulfur Colloid and Lidocaine Hydrochloride ( n = 3) Time after Preparation (hr) Radiochemical Purity (%) Retention of Radioactivity by 0.1-μm Filter (%) pH 0 99.5 ± 0.3 67.1 ± 3.7 4.8 ± 0.3 1 99.1 ± 0.2 65.4 ± 0.9 5.3 ± 0.3 2 99.3 ± 0.3 63.9 ± 1.4 5.3 ± 0.3 4 99.9 ± 0.1 67.4 ± 1.4 5.3 ± 0.3 8 99.2 ± 0.1 64.7 ± 2.8 5.3 ± 0.3 Time after Preparation (hr) Radiochemical Purity (%) Retention of Radioactivity by 0.1-μm Filter (%) pH 0 99.5 ± 0.3 67.1 ± 3.7 4.8 ± 0.3 1 99.1 ± 0.2 65.4 ± 0.9 5.3 ± 0.3 2 99.3 ± 0.3 63.9 ± 1.4 5.3 ± 0.3 4 99.9 ± 0.1 67.4 ± 1.4 5.3 ± 0.3 8 99.2 ± 0.1 64.7 ± 2.8 5.3 ± 0.3 Open in new tab Table 1. Mean ± S.D. Radiochemical Purity, Particle Size, and pH of Mixture of Technetium Tc 99m Sulfur Colloid and Lidocaine Hydrochloride ( n = 3) Time after Preparation (hr) Radiochemical Purity (%) Retention of Radioactivity by 0.1-μm Filter (%) pH 0 99.5 ± 0.3 67.1 ± 3.7 4.8 ± 0.3 1 99.1 ± 0.2 65.4 ± 0.9 5.3 ± 0.3 2 99.3 ± 0.3 63.9 ± 1.4 5.3 ± 0.3 4 99.9 ± 0.1 67.4 ± 1.4 5.3 ± 0.3 8 99.2 ± 0.1 64.7 ± 2.8 5.3 ± 0.3 Time after Preparation (hr) Radiochemical Purity (%) Retention of Radioactivity by 0.1-μm Filter (%) pH 0 99.5 ± 0.3 67.1 ± 3.7 4.8 ± 0.3 1 99.1 ± 0.2 65.4 ± 0.9 5.3 ± 0.3 2 99.3 ± 0.3 63.9 ± 1.4 5.3 ± 0.3 4 99.9 ± 0.1 67.4 ± 1.4 5.3 ± 0.3 8 99.2 ± 0.1 64.7 ± 2.8 5.3 ± 0.3 Open in new tab Discussion Although originally introduced as a liver and spleen imaging agent, technetium Tc 99m sulfur colloid is primarily used for gastrointestinal imaging studies, lymphatic mapping, and sentinel lymph node biopsy. Currently, the only commercially available kit for preparing technetium Tc 99m sulfur colloid is CIS-Sulfur Colloid.a Although a number of studies have evaluated the stability of this preparation after variations in the recommended procedure for compounding, including shortened heating times and filtration of the final preparation, this study evaluated the effects of storage (for up to eight hours) of the technetium Tc 99m sulfur colloid–lidocaine mixture to determine the effects of adding this local anesthetic to the syringe. Visual observation with nitrazine paper indicated no substantial pH changes in the preparation over time. All values remained within the pH range specified by USP for technetium Tc 99m sulfur colloid. The average particle size of technetium Tc 99m sulfur colloid is 0.3–0.5 μm (300–500 nm),11,16 and the size range can vary from <0.03 to >10 μm.12 Filtration of this preparation through a 0.1-μm membrane led to the retention of an average of 65.7% of the radioactivity, a percentage similar to that reported by others.11,12,14 More important, this value did not increase with storage time, indicating that the particles did not substantially increase in size. Radiochemical purity test results indicated no substantial change in the chemical form of the radioactivity over time. The average radiochemical purity was greater than 99%, far exceeding the USP specification of 92%. This study found a higher radiochemical purity initially and over time than earlier studies. Corrigan et al.13 reported radiochemical purity values of 83–86% for filtered technetium Tc 99m sulfur colloid that did not change over six hours. Hung et al.11 reported a reduction in radiochemical purity when a filtration step was included for the final preparation. Higher radiochemical purity for filtered technetium Tc 99m sulfur colloid was reported by Ponto,14 although that study indicated a reduction in radiochemical purity over eight hours from 99.3% to 98.6%. Reduced radiochemical purity may be caused by differences in compounding procedures, differences in radiochemical testing methods, or both. For example, using a shorter heating time to limit particle-size growth is generally recognized as reducing radiochemical purity.12,13 The present results indicate that adding lidocaine to technetium Tc 99m sulfur colloid did not substantially change radiochemical purity over the storage period. The in vitro stability of technetium Tc 99m sulfur colloid appears to remain unchanged in the presence of lidocaine. This suggests that the local anesthetic may continue to be used to ease patient discomfort during injections of technetium Tc 99m sulfur colloid for lymphoscintigraphy and sentinel lymph node biopsy. Conclusion Adding 0.2 mL of lidocaine hydrochloride 1% to syringes containing technetium Tc 99m sulfur colloid and storing the syringes for up to eight hours, such that the radioactivity at each storage time was 0.4 mCi, did not affect the radiochemical purity of the mixture. The pH of the mixture did not change substantially over time, nor did the amount of radioactivity retained by a 0.1-μm filter. a CIS-US Inc., Bedford, MA, lots 6422 and 6424. b 0.9% Sodium Chloride Injection, USP Hospira, Inc., Lake Forest, IL, lot 51-511-DK. c Xylocaine 1%, Hospira, Inc., lot not recorded. d ITLC-SG, Gelman, Ann Arbor, MI. e Millex-VV, Millipore Corporation, Bedford, MA. f Sterile Water for Injection, USP Hospira, Inc., lot 49-153-DK. References 1 Keshtgar MR, Ell PJ. Sentinel lymph node detection and imaging. Eur J Nucl Med . 1999 ; 26 : 57 –67. Crossref Search ADS PubMed 2 Alazraki N, Glass EC, Castronovo F et al. Procedure guideline for lymphoscintigraphy and the use of intraoperative gamma probe for sentinel lymph node localization in melanoma of intermediate thickness. J Nucl Med . 2002 ; 43 : 1414 –8. PubMed 3 Williams BS, Hinkle GH, Douthit RA et al. Lymphoscintigraphy and intraoperative lymphatic mapping of sentinel lymph nodes in melanoma patients. J Nucl Med Technol . 1999 ; 27 : 309 –17. PubMed 4 Schrenk P, Wayand W. Sentinel-node biopsy in axillary lymph-node staging for patients with multicentric breast cancer. Lancet. 2001 ; 357 : 122 . Letter. Crossref Search ADS PubMed 5 Kramer EL. Lymphoscintigraphy: radiopharmaceutical selection and methods. Nucl Med Biol . 1990 ; 17 : 57 –63. 6 Eshima D, Fauconnier T, Eshima L et al. Radiopharmaceuticals for lymphoscintigraphy: including dosimetry and radiation considerations. Semin Nucl Med . 2000 ; 30 : 25 –32. Crossref Search ADS PubMed 7 Wilhelm AJ, Mijnhout GS, Franssen EJ. Radiopharmaceuticals in sentinel lymph node detection—an overview. Eur J Nucl Med . 1999 ; 26 (suppl): S36 –42. Crossref Search ADS PubMed 8 Glass EC, Essner R, Morton DL. Kinetics of three lymphoscintigraphic agents in patients with cutaneous melanoma. J Nucl Med . 1998 ; 39 : 1185 –90. PubMed 9 Povoski SP, Olsen JO, Young DC et al. Prospective randomized clinical trial comparing intradermal, intraparenchymal and subareolar injection routes for sentinel lymph node mapping and biopsy in breast cancer. Ann Surg Oncol . 2006 ; 13 : 1412 –21. Crossref Search ADS PubMed 10 Dunnwald LK, Mankoff DA, Byrd DR et al. Technical aspects of sentinel node lymphoscintigraphy for breast cancer. J Nucl Med Technol . 1999 ; 27 : 106 –11. PubMed 11 Hung JC, Wiseman GA, Wahner HW et al. Filtered technetium-99m-sulfur colloid evaluated for lymphoscintigraphy. J Nucl Med . 1995 ; 36 : 1895 –901. PubMed 12 Eshima D, Eshima LA, Gotti NM et al. Technetium-99m-sulfur colloid for lymphoscintigraphy: effects of preparation parameters. J Nucl Med . 1996 ; 37 : 1575 –8. PubMed 13 Corrigan P, Eshima L, Eshima D. Stability of filtered Tc-99m sulfur colloid for lymphoscintigraphy. J Nucl Med Technol. 1997 ; 25 : 153 . Abstract. 14 Ponto JA. Stability of filtered technetium Tc-99m sulfur colloid. J Am Pharm Assoc . 2005 ; 45 : 92 –4. Crossref Search ADS 15 Cis-Sulfur Colloid (kit for the preparation of technetium Tc-99m sulfur colloid injection diagnostic for intravenous and oral use) package insert. Bedford, MA: CIS-US; 1999 Jul. 16 Alex JC, Krag DN. Gamma-probe-guided localization of lymph nodes. Surg Oncol . 1993 ; 2 : 137 –44. Crossref Search ADS PubMed 17 Vivian A, Ice RD, Shen V et al. Technical bulletin 32: radiochemical purity of radiopharmaceuticals using Gelman Se-prachrom (ITLC) chromatography. Ann Arbor, MI: Gelman Instrument; 1977 . 18 Quality control and radiopharmaceuticals. In: Chilton HM, Witcofski RL, eds. Nuclear pharmacy: an introduction to the clinical application of radiopharmaceuticals. Philadelphia: Lea & Febiger; 1986 :71–82. 19 Davis MA, Jones AG, Trindale H. A rapid and accurate method for sizing radiocolloids. J Nucl Med . 1974 ; 15 : 923 –8. PubMed 20 Pederson B, Kristensen K. Evaluation of methods for sizing of colloidal radiopharmaceuticals. Eur J Nucl Med . 1981 ; 6 : 521 –6. PubMed 21 Technetium Tc 99m sulfur colloid injection. In: The United States pharmacopeia, 30th rev., and The national formulary, 25th ed. Rockville, MD: United States Pharmacopeial Convention; 2007 :3288. Copyright © 2007, American Society of Health-System Pharmacists, Inc. All rights reserved.
TI - Stability of a mixture of technetium Tc 99m sulfur colloid and lidocaine hydrochloride
JF - American Journal of Health-System Pharmacy
DO - 10.2146/ajhp070193
DA - 2007-12-01
UR - https://www.deepdyve.com/lp/oxford-university-press/stability-of-a-mixture-of-technetium-tc-99m-sulfur-colloid-and-wGjFDg0GwH
SP - 2477
VL - 64
IS - 23
DP - DeepDyve
ER -