PET/CT imaging of osteoblastic bone metastases with 68Ga-bisphosphonates: first human study

Abstract

Bisphosphonates are well established ligands for 99m Tc for planar and SPECT/CT imaging of osteoblastic metastases. A novel DOTA-based bisphosphonate, (4-{[bis-(phosphonomethyl)) carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid (BPAMD) [1,2] The advantages of this new bone imaging PET tracer are the very high target to soft tissue ratios and fast clearance, its ease of use and the generator-based availability of 68 Ga which becomes especially important in these days of 99m Tc shortage.While 18 F-fluoride is adsorbed on bone surface and is related to blood flow, the bisphosphonate [ 68 Ga]BPAMD is taken up also by osteoclasts reflecting the farnesyl diphosphate synthase enzyme dynamics in the HMG-CoA reductase pathway. Since this pathway is mainly responsible for the osteoclastic bone destruction, [ 68 Ga]BPAMD may be superior in osteoclastic lesions.Finally, [ 68 Ga]BPAMD seems to be an ideal PET/CT tracer to plan and monitor bisphosphonate therapy in several bone disorders like osteoporosis, osteitis deformans, bone metastases, multiple myeloma, osteogenesis imperfecta, etc. and also to monitor radionuclide therapy for palliation of bone pain.Acknowledgments Support by the EC through COST actions D38 and BM0607 is gratefully acknowledged.

Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

“…However, they stated that the advantage of 68 Ga-EDTMP over [ 18 F]-fluoride was not apparent and that the future clinical prospect of 68 Ga-EDTMP remained speculative. Meanwhile, PET/CT imaging of bone metastases with a 68 Ga-DOTA complex-conjugated bisphosphonate (BPAMD) based on a strategy similar to our study has been reported [29]. 68 Ga-BPAMD showed high uptake in osteoblastic metastases.…”

Preparation and biological assessment of 177Lu-BPAMD as a high potential agent for bone pain palliation therapy: comparison with 177Lu-EDTMP

“…Distinct values of the complex ligands (100-400 nmol) were added to the lutetium-containing vials. By varying pH (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and temperature (50-100°C), the effect of these parameters was investigated based on ITLC results. For radio thin layer chromatography, a 5 lL sample of the final fraction was spotted on a chromatography Whatman No.…”

“…(4-{[(bis(phosphonomethyl))carbamoyl] methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid (BPAMD) (Fig. 1), as a new macrocyclic diphosphonate, in labeling with 68 Ga, in first human studies showed promising results such as very high target-tosoft-tissue ratios and ultrafast clearance [12]. It has been shown that the BPAMD complex, as a new generation of DOTA bisphosphonate, can solve the mentioned limitations of the first generation phosphonates either in diagnostic or in therapeutic applications [11].…”

Estimated human absorbed dose for 68Ga-ECC based on mice data: comparison with 67Ga-ECC

“…Briefly, distinct values of the complex ligands were added to the 68 Ga-containing vials. By varying pH (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and temperature (50-100°C), the effect of these parameters was investigated based on ITLC results. The optimal procedure for the preparation of 68 Ga-ECC complex with a high labeling yield was obtained.…”

“…The efficacies of 68 Ga-based tracers are comparable to that of 18 F-based agents and have stimulated researchers to investigate the potential of 68 Ga-based PET imaging agents [4] and nowadays, numerous 68 Ga-based radiopharmaceuticals have been found useful in clinical studies [5][6][7].…”