Evaluation of biodistribution by local versus systemic administration of 99mTc-labeled pamidronate.
BACKGROUND
There is an emerging interest in utilizing local and systemic administration of bisphosphonates in orthopedics. The primary objective of this study was to use (99m)Tc-pamidronate ((99m)Tc-PAM) as a tool and compare bone and tissue uptake by local versus systemic administration.


METHODS
(99m)Tc-PAM was administered intravenously (i.v.), subcutaneously (s.c.) and by direct application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The animals were imaged at 2 h and 24 h after administration and then killed. Organs were harvested, and their radioactivity was estimated. Specific uptake in the right femur was compared between groups, as was systemic exposure to (99m)Tc PAM.


RESULTS
Bone uptake of (99m)Tc-PAM in the i.v. and s.c. groups was 2.2 +/- 0.15 and 0.65 +/- 0.07% ID/g, respectively, at the 2 h time point. Uptake by surgically exposed right femur (d.a) was 5.15 +/- 0.26% ID/g, 134% higher than the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone when the femur was fractured (d.a.#f), the uptake was 7.89 +/- 0.46% ID/g, a further 50% increase (P < 0.05). The uptake of (99m)Tc-PAM increased after 24 h of application to 2.4 +/- 0.15, 1.53 +/- 0.09, 7.94 +/- 0.99, and 13.2 +/- 0.80% ID/g) for i.v., s.c., d.a., and d.a.#f methods, respectively. The increases in uptake for the d.a. methods were significantly higher than for the local methods at the 24-h time point (P < 0.05). Although renal uptake was comparable with the i.v. and s.c. methods (0.22 +/- 0.03 and 0.22 +/- 0.04% ID/g), it was significantly lower with the d.a. methods (0.05 +/- 0.07 and 0.16 +/- 0.07% ID/g) (P < 0.05). The corresponding urinary excretion was 55%, 45%, 36%, and 35% of the injected dose at 24 h.


CONCLUSIONS
The results indicate that the bone uptake of (99m)Tc-PAM was significantly higher (P = 0.001) and the kidney uptake significantly lower (P = 0.004) with the d.a. methods than with the i.v. or s.c. method. The findings indicate the need for further study into the potential of local administration of bisphosphonates in the presence of orthopedic indications.
Kumar
Divesh
D
Department of Nuclear Medicine, University of Macquarie, Department of Biological Science, The Children's Hospital at Westmead and the Westmead Hospital, Westmead, Australia.
Kumar
Vijay
V
Little
David G
DG
Howman-Giles
Robert B
RB
Wong
Effie
E
Ali
Sinan O
SO
D000287:Administration, Topical; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D020558:GTP Phosphohydrolases; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D000077268:Pamidronate; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium / Q000008:administration & dosage / Q000493:pharmacokinetics*
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D013667:Technetium; D020558:GTP Phosphohydrolases; D000077268:Pamidronate