Normal and Abnormal Patterns of 99mTc Pertechnetate Distribution in Meckel’s Scans Educational Robert Huynh, PharmD; Jorge Oldan, MD; Mitchel Muhleman, MD; Eric Smith, PharmD; Amir H. Khandani, MD Exhibit UNC School of Medicine Radiology Department  Nuclear Medicine Division  University of North Carolina at Chapel Hill, NC

Introduction 99mTc Pertechnetate Scintigraphy Delayed Clearance Discussion Next Steps

The Meckel’s scan is well-regarded for its straightforward execution, Physical Properties A. 14 y/o M B. 16 y/o M C. 33 m/o M D. 19 y/o F • Other mechanisms outside of colloid formation and labeling of blood Formal IRB-Approved Investigation simple radiopharmaceutical preparation, and high diagnostic accuracy. constituents may account for the observed anomalies. For example, • Abnormal 99mTc pertechnetate distribution has been observed in The fact that the procedure only requires 99mTc pertechnetate, eluted 99m In the decay of 99mTc, use of bacteriostatic saline as diluent can lead to increased activity in Tc (t1/2 = 6.01 h) 0.1427 several other patients at our institution. directly from the generator and free of any additional radiochemical three gamma (γ) muscle, liver, and/or blood pool.8 However, our pharmacy only uses processing, would suggest that abnormal patterns of radiotracer γ1 photons are released preservative-free saline. • Exploratory study (retrospective chart review) underway to identify 0.1405 distribution should not be expected. However, we have observed with energies of 0.0022 • With QC testing demonstrating low quantities of hydrolyzed- other potential contributing factors. 99m Select cases of delayed clearance observed during Meckel’s scans at our abnormal patterns of Tc pertechnetate distribution with instances of MeV (γ1),0.1405 MeV reduced technetium (<1% per elution), it is an unlikely contributor to Intra- and Inter-Patient Correlations γ3 (γ ), and 0.1427 MeV institution. On static delayed images, diffuse activity is still prominent delayed clearance from the liver and cardiac blood pool. Beyond the γ 2 the observed pattern of distribution. 99m 2 • Meckel’s scan, Tc pertechnetate is extensively utilized in nuclear (γ3). The most in the liver (patients A – D) and cardiac blood pool (patients B – D) at 15 Intra-patient: patient D with two Meckel’s scans spaced 3 months 99m • Labeling of RBCs or another blood component cannot be ruled out 99m medicine, making it even more important to recognize the possibility of abundant of these, γ2, minutes. In a typical pattern of Tc pertechnetate distribution, the apart showing similar patterns of Tc pertechnetate distribution. and would account for both blood pool and liver activity; possible its altered biodistribution and delayed clearance 99 5 accounts for 89% of all tracer rapidly clears from the liver and blood pool after distribution Refutes the idea that the issue is related to product quality. Tc (t1/2 = 2.11 x 10 y) 0.0 (within several minutes) due to lack of uptake. mechanisms for blood labeling are observed in each patient: nuclear transitions. • Inter-patient: diverging patterns of distribution (i.e. one normal, one 99m Objectives Root Cause Analysis − Patient A takes a lipophilic drug capable of crossing the blood-brain abnormal) between two Meckel’s patients receiving the same Tc Biodistribution barrier (BBB), and likely erythrocyte membranes as well. However, the pertechnetate lot would lend additional support against QC issues. Identifying possible causes of delayed clearance in liver and cardiac case report by Vento et al. involved significant polypharmacy, where However, no such cases have yet been observed. 1) Summarize the etiology, epidemiology, and pathophysiology of 99mTc is collected from the 99Mo generator in the chemical 12 blood pool might reasonably begin with consideration of known multiple lipophilic medications were identified. This may be Meckel’s diverticulum. form of NaTcO (sodium pertechnetate). Pertechnetate has • Similar cases to be reviewed. 4 techniques for visualizing these targets. important in providing a significant source of metal ions or other points 2) Describe the normal, physiologic patterns of radiotracer an atomic radius comparable to iodide and, when of attachment for pertechnetate within the RBC. distribution after intravenously administered 99mTc pertechnetate. administered intravenously, distributes primarily to the Agent Mechanism − Patient B received a dextrose infusion prior to the Meckel’s scan and Conclusion thyroid, salivary glands, choroid plexus, bladder, and 3) Discuss the pathophysiologic basis for 99mTc pertechnetate uptake 99mTc SC Phagocytosis of colloidal particles by macrophages takes a lipophilic medication capable of penetrating the BBB. Also • 99mTc pertechnetate accumulates in gastric tissue and can be used to stomach. Liver takes two medications containing aluminum in color additives. in Meckel’s diverticulum. (sulfur colloid) (Kupffer cells) of reticuloendothelial system. identify Meckel’s diverticula with ectopic gastric mucosa. It should Since it accumulates in the mucoid cells of gastric mucosa, 99mTc RBCs; Visualization of labeled blood component’s − Patient C takes several lipophilic drugs and two medications not demonstrate persistent liver or cardiac blood pool activity. 4) Recognize cases of abnormal 99mTc pertechnetate distribution and Blood pertechnetate is useful in detecting Meckel’s diverticulum 99mTc HSA (albumin) dispersion through vasculature and heart chambers. containing aluminum in color additives. • clearance in Meckel’s scans. when it contains functional ectopic gastric tissue.1 Gastric Since Meckel’s diverticulum can occur anywhere in the abdomen, − Patient D received a dextrose infusion and two lipophilic drugs. activity in the cardiac blood pool and liver may interfere with the 5) Identify potential causes of abnormal 99mTc pertechnetate uptake can be increased via premedication with agents The agents listed provide clues to the nature of the potential cause(s) – 99m − Tin was not identified as an excipient in any of our patients’ interpretation of a 99mTc pertechnetate scan. distribution and clearance in Meckel’s scans. including H2R antagonists and pentagastrin. namely, 1) liver activity may be due to presence of a Tc-associated medications. None of the patients had received tin-containing colloidal impurity, and 2) inadvertent labeling of any blood component • Quality control of radiopharmaceuticals is critical in a nuclear The estimated sensitivity and specificity of this procedure 99m radiopharmaceuticals for a prior study. Biodistribution of with Tc would contribute to blood pool activity. Various mechanisms, 99m 4 medicine clinic and can quickly rule out causes when problems arise. Tc pertechnetate. in detecting Meckel’s is 89.6% and 97.1%, respectively. 2 Meckel’s Diverticulum in turn, may account for these processes. − None of the patients were on antimicrobial therapy at the time of study. • Lipophilic medications seems to be a common factor in our case series, but our series is small. It is possible that no single factor can An outpouching of the ileum first described in 1812 by Case Study Colloidal Hydrolyzed-reduced (HR) technetium: an insoluble colloid German anatomist Johann Friedrich Meckel.1 impurities resulting from radiolytic decomposition or reduction and Other Drug-Pertechnetate Interactions13,14 explain all cases of abnormal distribution. disproportionation of 99mTc. However, daily quality control (QC) Patient background: 8 month old female with hx of BRBPR. • tests demonstrate presence of HR species to be less than 1%. Note: several drug-pertechnetate interactions are outside the context Alternatively, this phenomenon might be the result of a complex Occurs when the omphalomesenteric (vitelline) duct Dose: 1.1 mCi 99mTc pertechnetate of Meckel’s diverticulum and are not presented here. interplay between several different factors, some of which may as fails to completely regress during gestation. yet be unidentified. Imaging: Anterior and posterior projections of the abdomen and Aluminum: complexation with pertechnetate leading to blood Blood tags Potentially Useful 99m pelvis, up to 30 minutes. pool retention. Daily QC tests demonstrate aluminum levels to Cimetidine (H2RA), Pentagrastrin • That Tc pertechnetate is extensively utilized in nuclear medicine Occurs in approximately 2% of the population and Increase pertechnetate accumulation in gastric parietal cells. underscores the importance of understanding its distributional is twice as common in males.1 be far below USP limits (10 ug/mL), but alternatives sources of Findings: On the static delayed images, activity is seen in the stomach aluminum are possible (e.g., Mylanta).5 behavior and diverse interactions with drugs and pathophysiology. at approximately 10 minutes with activity progressing into the proximal Glucagon 99m May be silent or symptomatic; the latter most small bowel. There is a focus (arrows) of increased radiotracer uptake Stannous (tin) ion: required for reduction of Tc and subsequent labeling Reduces peristaltic movement in the region around potential References commonly presents in children. in the abdomen just to the right of midline superior to the bladder, of RBCs, albumin, or another blood component. Tin from any external source, Meckel’s diverticulum to enhance pertechnetate accumulation. including prior administration of radiopharmaceuticals, may alter the 1. Irvine I, Doherty A, Hayes R. Bleeding meckel's diverticulum: A study of the accuracy of pertechnetate scintigraphy as a diagnostic tool. Eur J Radiol. 2017 consistent with a gastric mucosa-containing Meckel's diverticulum. Nov;96:27-30. biodistribution of 99mTc pertechnetate.6,7,8,9 2. Hansen C, Søreide K. Systematic review of epidemiology, presentation, and management of Meckel's diverticulum in the 21st century. Medicine (Baltimore). 2018 May contain ectopic tissue; gastric and pancreatic Aug; 97(35): e12154. Undesirable 3. Meckel’s diverticulum anatomical location image credit: https://www.mhealth.org/patient-education/90410 Perchlorate 99m tissues account for 97% of all ectopic tissues, with Dextrose: erroneous dilution of pertechnetate with 5% dextrose results in 4. Biodistribution of Tc image credit: http://jnm.snmjournals.org/content/58/5/791.long 2 ANT 15 min POST 10 min ANT 30 min POST 30 min 5. Wang TS, Fawwaz RA, Esser PD, Johnson PM. Altered body distribution of [99mTc] pertechnetate in iatrogenic hyperaluminemia. J Nucl Med. 1978 Apr;19(4):381-3. gastric being the most common. 99m Inhibits pertechnetate uptake in various tissues (including gastric). 6. McRae J, Sugar RM, Shipley B, Hook GR. Alterations in tissue distribution of 99mTc-pertechnetate in rats given stannous tin. J Nucl Med. 1974 Mar;15(3):151-5. the altered biodistribution of Tc radiopharmaceuticals – including to 7. Khentigan A, Garrett M, Lum D, Winchell HS. Effects of prior administration of Sn(II) complexes on in vivo distribution of 99mTc-pertechnetate. J Nucl Med. 1976 Anatomical location of May;17(5):380-4. 3 99m 10 Meckel’s diverticulum. cardiac blood pool – possibly due to Tc-labeled dextrose. Aluminum 8. Ponto, JA. Preparation and Dispensing Problems Associated with Technetium Tc-99m Radiopharmaceuticals. Correspondence Continuing Education Courses for Symptomatic cases typically involve intestinal Nuclear Pharmacists and Nuclear Medicine Professionals. 99m Confines distribution of pertechnetate to vascular space. 9. Yen CK, Lanoie Y. Effect of stannous pyrophosphate red blood cell gastrointestinal bleeding scan on subsequent Meckel's scan. Clin Nucl Med. 1992 Jun;17(6):454- obstruction, GI hemorrhage, or inflammation of the Antimicrobials: therapy during administration of Tc pertechnetate has 6. 2 11 10. Al-Enizi E, Kazem N, Owunwanne A, Collier BD, Mathew M. Dextrose solutions yield radiochemical impurities: the "sweet" scans. J Nucl Med Technol. 2003 diverticulum. been associated with in vivo labeling of erythrocytes. Mar;31(1):33-6. Laxatives 11. Castronuovo JJ, Chervu LR, Milstein DM. Altered distribution of technetium-99m sodium pertechnetate associated with antimicrobial therapy. Clin Nucl Med. 1985 99m Dec;10(12):868-71. Lipophilic drugs: mediate entry of Tc pertechnetate across cell Induces localized abdominal uptake of pertechnetate, potentially 12. Vento JA, Swing LS, Spencer RP. Persistent binding of Tc-99m pertechnetate to erythrocytes in a patient receiving multiple pharmaceuticals. Clin Nucl Med. 2000 Symptomatic cases are managed via resection. The role of 12 Feb;25(2):152-3. membranes and into erythrocytes, esp. in cases of polypharmacy. leading to falsely positive Meckel’s scans. 13. Hesslewood S, Leung E. Drug interactions with radiopharmaceuticals. Eur J Nucl Med. 1994 Apr;21(4):348-56. prophylactic resection in silent cases is unclear. 14. Hladik WB 3rd, Nigg KK, Rhodes BA. Drug-induced changes in the biologic distribution of radiopharmaceuticals. Semin Nucl Med. 1982 Apr;12(2):184-218.