68Ga-P15-041, A Novel Bone Imaging Agent for Diagnosis of Bone Metastases

Abstract

Objectives68Ga-P15-041 (68Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer, which can be readily prepared by using a simple kit formulation and an in-house 68Ga/68Ge generator. The aim of this study is to assess the potential human application of 68Ga-P15-041 for clinical PET/CT imaging and to compare its efficacy to detect bone metastases of different cancers with 99mTc-MDP whole-body bone scintigraphy (WBBS).MethodsInitial kinetic study using Patlak analysis and parametric maps were performed in five histopathologically proven cancer patients (three males, two females) using 68Ga-P15-041 PET/CT scan only. Another group of 51 histopathologically proven cancer patients (22 males, 29 females) underwent both 99mTc-MDP WBBS and 68Ga-P15-041 PET/CT scans within a week, sequentially. Using either pathology examination or follow-up CT or MRI scans as the gold standard, the diagnostic efficacy and receiver operating characteristic curve (ROC) of the two methods in identifying bone metastases were compared (p <0.05, statistically significant).ResultsFifty-one patients were imaged, and 174 bone metastatic sites were identified. 68Ga-P15-041 PET/CT and 99mTc-MDP WBBS detected 162 and 81 metastases, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 68Ga-P15-041 PET/CT and 99mTc-MDP WBBS were 93.1% vs 81.8%, 89.8% vs 90.7%, 77.5% vs 69.2%, 97.2% vs 93.4% and 90.7% vs 88.4%, respectively. Our results showed that the mean of SUVmax was significantly higher in metastases than that in benign lesions, 15.1 ± 6.9 vs. 5.6 ± 1.3 (P <0.001). Using SUVmax = 7.6 as the cut-off value by PET/CT, it was possible to predict the occurrence of metastases (AUC = 0.976; P <0.001; 95% CI: 0.946–0.999). However, it was impossible to distinguish osteoblastic bone metastases from osteolytic bone lesions. Parametric maps based on Patlak analysis provided excellent images and highly valuable quantitative information.Conclusions68Ga-P15-041 PET/CT, offering a rapid bone scan and high contrast images in minutes, is superior to the current method of choice in detecting bone metastases. It is reasonable to suggest that 68Ga-P15-041 PET/CT could become a valuable routine nuclear medicine procedure in providing excellent images for detecting bone metastases in cancer patients. 68Ga-P15-041 could become a valuable addition expanding the collection of 68Ga-based routine nuclear medicine procedures where 18F fluoride is not currently available.

Theranostic Agent Targeting Bone Metastasis: A Novel [68Ga]Ga/[177Lu]Lu-DOTA-HBED-bisphosphonate

“…This agent was an extension of previously reported [ 68 Ga]­Ga-HBED-CC-bisphosphonate ([ 68 Ga]­Ga-P15-041), successfully applied in detecting bone lesions associated with tumor metastasis in cancer patients. , We aim to extend the application of this ligand to the treatment of bone metastases by labeling it with therapeutic radionuclides, such as lutetium-177, actinium-225, and others. Although it was reported that Lu­(III) forms a complex with HBED with high stability constant (logKd = 20.4), no further [ 177 Lu]­Lu-HBED-CC-related complexes are mentioned in the literature.…”

“…Previously, a bone imaging agent, ([ 68 Ga]­Ga-HBED-CC-bisphosphonate, [ 68 Ga]­Ga-P15-041), containing HBED-CC and bisphosphonate groups was prepared (Figure ) and it showed excellent bone uptake and efficient detection of bone metastasis in cancer patients. , By adding an additional DOTA chelator, P15-041 was converted to P15-073, 1 , which can accommodate different α- or β – -emitting metals, i.e., lutetium­(III)-177, actinium­(III)-225, and other metal-based radionuclides, for the formation of stable complexes as bone-seeking drugs (Figure ). The desired DOTA-HBED-CC-bisphosphonate (P15-073, 1 ) contains two chelators: DOTA and HBED-CC.…”

Application Progress of the Single Domain Antibody in Medicine

“…As smaller, intact, functional antigen binding agents with a small size (12–15 kDA), nanobodies demonstrate strong tissue penetration and high affinity and stability, revealing treatment pharmacokinetics and pharmacodynamics compatible with short-lived radioisotopes. They are more suitable for tracking advanced tumors [ 81 , 82 , 83 ].…”

Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy

“…39−41 A bisphosphonate ([ 68 Ga]Ga-P15-041) has been tested in humans for imaging bone metastasis. 25,26,42 Using DOTA derivatives as the chelator and the same PSMA binding moiety and linker (Glu-NH-CO-NH-Lys-Phe-O-carboxymethyl)-Tyr-= X in blue) from the diagnostic agent, [ 68 Ga]Ga-P16-093, [ 177 [ 177 Lu]Lu-1 displayed superior dual-targeting properties and therefore may be a promising new therapeutic agent for prostate cancer, targeting both PSMA tumors and bone metastases.…”

“…A PSMA-targeting imaging agent, [ 68 Ga]­Ga-P16–093, was successfully prepared , and tested in humans. − A bisphosphonate ([ 68 Ga]­Ga-P15-041) has been tested in humans for imaging bone metastasis. ,, Using DOTA derivatives as the chelator and the same PSMA binding moiety and linker (Glu-NH-CO-NH-Lys-Phe- O -carboxymethyl)-Tyr- = X in blue) from the diagnostic agent, [ 68 Ga]­Ga-P16-093, [ 177 Lu]­Lu-P19-065 (Approach #1) and [ 177 Lu]­Lu-P17–087, [ 177 Lu]­Lu-P17-088 (Approach #2) were successfully transformed to radionuclide therapy agents. To develop hetero-bivalent agents, R = Gly-bisphosphonate was added for targeting bone metastasis, resulting in the formation of hetero-bivalent agents, [M]-P17-079 ([M]-1) and [M]-P17-081 ([M]-2) with [M] = [ 68 Ga/ 177 Lu].…”