PMID- 17013741 OWN - NLM STAT- MEDLINE DCOM- 20070130 LR - 20181201 IS - 0949-2658 (Print) IS - 0949-2658 (Linking) VI - 11 IP - 5 DP - 2006 Oct TI - Evaluation of biodistribution by local versus systemic administration of 99mTc-labeled pamidronate. PG - 512-20 AB - 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. FAU - Kumar, Divesh AU - Kumar D AD - Department of Nuclear Medicine, University of Macquarie, Department of Biological Science, The Children's Hospital at Westmead and the Westmead Hospital, Westmead, Australia. FAU - Kumar, Vijay AU - Kumar V FAU - Little, David G AU - Little DG FAU - Howman-Giles, Robert B AU - Howman-Giles RB FAU - Wong, Effie AU - Wong E FAU - Ali, Sinan O AU - Ali SO LA - eng PT - Journal Article PL - Japan TA - J Orthop Sci JT - Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association JID - 9604934 RN - 0 (Bone Density Conservation Agents) RN - 0 (Diphosphonates) RN - 7440-26-8 (Technetium) RN - EC 3.6.1.- (GTP Phosphohydrolases) RN - OYY3447OMC (Pamidronate) SB - IM MH - Administration, Topical MH - Animals MH - Bone Density Conservation Agents/administration & dosage/*pharmacokinetics MH - Diphosphonates/administration & dosage/*pharmacokinetics MH - Disease Models, Animal MH - Femoral Fractures/diagnostic imaging/drug therapy/metabolism MH - Femur/diagnostic imaging/drug effects/*metabolism MH - GTP Phosphohydrolases MH - Injections, Intravenous MH - Injections, Subcutaneous MH - Male MH - Pamidronate MH - Radionuclide Imaging MH - Rats MH - Rats, Wistar MH - Technetium/administration & dosage/*pharmacokinetics EDAT- 2006/10/03 09:00 MHDA- 2007/01/31 09:00 CRDT- 2006/10/03 09:00 PHST- 2006/02/02 00:00 [received] PHST- 2006/05/24 00:00 [accepted] PHST- 2006/10/03 09:00 [pubmed] PHST- 2007/01/31 09:00 [medline] PHST- 2006/10/03 09:00 [entrez] AID - S0949-2658(15)32510-0 [pii] AID - 10.1007/s00776-006-1046-5 [doi] PST - ppublish SO - J Orthop Sci. 2006 Oct;11(5):512-20. doi: 10.1007/s00776-006-1046-5.