Biodistribution of Gallium-68-Labeled DOTA-Bisphosphonates

Aim:

Main indications of oncologic skeletal imaging are metastatic diseases in skeleton, bone pain in patients with known cancer, and primary bone tumors. Benign bone diseases like pediatric/adult back pain, bone viability and Paget’s disease are also important indications of skeletal imaging. There are numerous studies with [¹⁸F]fluoride PET demonstrating the clinical utility. Similar characteristics show Tc-99m-labeled bisphosphonates. Combining the bone seeking properties, the advantages of PET, and the potential labeling with therapeutic radionuclides we studied DOTA-phosphonates radiolabeled with [⁶⁸Ga]Ga3+.
Methods:
The following macrocyclic tetraaza based phosphonate chelators were used BPAMD ((4–{[(bis-phosphonomethyl) carbomoyl]methyl}–7,10–bis–(carboxymethyl)–1,4,7,10-tetraazacyclododec–1–yl)–acetic acid, BPAPD ((4–{[(bis–phosphonopropyl)carbomoyl]methyl}–7,10–bis–(carboxymethyl)–1,4,7,10-tetraazacyclododec–1–yl)–acetic acid and BPPED Tetraethyl 10-{[(2,2-bis-phosphonoethyl)hydroxyphosphoryl]methyl}-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid. The DOTA based phosphonate ligands were labeled with [⁶⁸Ga]GaCl₃. The radiochemical purity of the labeled products was >95% determined with radio thin-layer chromatography. The biodistribution and biokinetics were compared with [¹⁸F]fluoride and [^99mTc]Tc-MDP in Wistar rats using dissection, small animal PET and SPECT. All activity concentration data were calculated as SUV.
Results:
The compounds were labeled with high yields in ammonium acetate buffer with ⁶⁸Ga, followed by a purification step using a cation exchange resin. High uptake values were detected for all ⁶⁸Ga-phosphonates in the femura. The accumulation of [⁶⁸Ga]BPPED in the bone was the highest and comparable with the uptake of [¹⁸F]Fluoride and [^99mTc]Tc-MDP. The blood clearance of the [⁶⁸Ga]BPPED was the fastest with a biexponential kinetics and half-life of 0.4 min and 6.9 min. The [⁶⁸Ga]BPPED bone to blood ratio was also superior, however, not so large like of [¹⁸F]Fluoride and [^99mTc]Tc-MDP.
Conclusion:
The [68Ga]BPPED showed in a preclinical setting excellent characteristics for skeletal imaging. It seems to be also a potential candidate for radionuclide therapy in oncology