Extravasation of hydroxymethylene diphosphonate-induced subcutaneous inflammation, histologically demonstrated in BALB/c mice.
We encountered local reactions at injection sites in 7 patients after an intravenous injection of (99m)Tc-hydroxymethylene diphosphonate ((99m)Tc-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 (99m)Tc-HDP injection and investigated the mechanism involved.


METHODS
Seven solutions were prepared: 0.1 M acetic acid, 0.1 M NaOH, 2.1 mM (99m)Tc-HDP, 4.7 mM (99m)Tc-methylene diphosphonate ((99m)Tc-MDP), 1.05 mM (99m)Tc-HDP diluted with normal saline, 37 MBq of (99m)Tc-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 (99m)Tc-HDP, 4.7 mM (99m)Tc-MDP, 1.05 mM (99m)Tc-HDP diluted with normal saline, 37 MBq (99m)Tc-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 (99m)Tc-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 (99m)Tc-MDP injection sites. On day 19, (99m)Tc-HDP injection sites appeared to have recovered and showed healed scars and almost-normal microscopic features.


CONCLUSIONS
Our results indicate that the local reaction induced by extravasation of (99m)Tc-HDP is probably caused by high acidity, and (99m)Tc-HDP should be administered carefully to avoid adverse reactions.
Lim
Ilhan
I
Department of Nuclear Medicine, Korea Cancer Center Hospital, Seoul, Korea.
Kang
Keon Wook
KW
Myung
Jae Kyung
JK
Jung
Kyeong Cheon
KC
Jeon
Yong Hyun
YH
Kang
Ji Yeon
JY
Kim
Young Hwa
YH
Chung
June-Key
JK
Lee
Dong Soo
DS
D000818:Animals; D004164:Diphosphonates / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology*; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000209:etiology* / Q000473:pathology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D015609:Organotechnetium Compounds / Q000009:adverse effects*
D004164:Diphosphonates; D015609:Organotechnetium Compounds; C060491:technetium Tc 99m hydroxydiphosphonate