RT Journal Article SR Electronic T1 Extravasation of Hydroxymethylene Diphosphonate–Induced Subcutaneous Inflammation, Histologically Demonstrated in BALB/c Mice JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1573 OP 1575 DO 10.2967/jnumed.110.078774 VO 51 IS 10 A1 Lim, Ilhan A1 Kang, Keon Wook A1 Myung, Jae Kyung A1 Jung, Kyeong Cheon A1 Jeon, Yong Hyun A1 Kang, Ji Yeon A1 Kim, Young Hwa A1 Chung, June-Key A1 Lee, Dong Soo YR 2010 UL http://jnm.snmjournals.org/content/51/10/1573.abstract AB We encountered local reactions at injection sites in 7 patients after an intravenous injection of 99mTc-hydroxymethylene diphosphonate (99mTc-HDP). Archived bone scans showed radiopharmaceutical extravasation at injection sites in all patients. To identify the mechanism underlying these local reactions, we challenged BALB/c mice with an 99mTc-HDP injection and investigated the mechanism involved. Methods: Seven solutions were prepared: 0.1 M acetic acid, 0.1 M NaOH, 2.1 mM 99mTc-HDP, 4.7 mM 99mTc-methylene diphosphonate (99mTc-MDP), 1.05 mM 99mTc-HDP diluted with normal saline, 37 MBq of 99mTc-pertechnetate, and normal saline. Six female BALB/c mice were subcutaneously injected in their backs with 0.04 mL of each solution. Backs were observed, and skin and subcutaneous tissues were acquired on days 5, 7, and 19 after injection. Two pathologists interpreted the histologic specimens. Results: The pH values of the 0.1 M acetic acid, 0.1 M NaOH, 2.1 mM 99mTc-HDP, 4.7 mM 99mTc-MDP, 1.05 mM 99mTc-HDP diluted with normal saline, 37 MBq 99mTc-pertechnetate, and normal saline were 3.28, 14.3, 4.79, 6.45, 6.16, 6.85, and 6.53, respectively. A slight redness was observed at 99mTc-HDP injection sites on day 5 after injection, and many inflammatory cells, such as neutrophils, were found to infiltrate subcutaneous tissues by light microscopy, suggesting active inflammation. However, no abnormality was found at 99mTc-MDP injection sites. On day 19, 99mTc-HDP injection sites appeared to have recovered and showed healed scars and almost-normal microscopic features. Conclusion: Our results indicate that the local reaction induced by extravasation of 99mTc-HDP is probably caused by high acidity, and 99mTc-HDP should be administered carefully to avoid adverse reactions.