New 68ga hbed-bisphosponates and their derivatives as bone imaging agents

Objectives Positron emission tomography (PET) imaging using 68Ga labeled bisphosphonates to target bone metastasis may be a valuable tool for cancer diagnosis and for monitoring therapeutic treatment.

Methods A series of 68Ga labeled derivatives of N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC) containing one bisphosphonate group (1a) or derivatives of bisphosphonate-HBED-CC containing conjugated 2-glucosamine (1b), glycine (1c), alanine (1d), aspartic acid (1e), and glutamic acid (1f) were prepared.

Results New HBED ligands, 1a-f, reacted rapidly in a sodium acetate buffer with [68Ga]GaCl3 eluted from a commercially available 68Ge/68Ga generator (pH 4, >95% labeling at room temperature in 5 min) to form [68Ga]1a-f. This labeling condition avoids the need for further purification. The biodistribution of [68Ga]1a-f in normal mice after an iv injection showed excellent bone uptake and retention comparable to that of [18F]NaF. MicroPET imaging studies in normal mice showed excellent uptake and retention for [68Ga]1a suggest that it is potentially a useful bone imaging for PET imaging.

Conclusions The results suggest that [68Ga]1a-f may be suitable as bone imaging agents in humans, serving as alternatives to the current bone imaging agent of choice, [18F]NaF and [99mTc]MDP. These new agents, [68Ga]1a-f, would provide practical in vivo bone imaging in conjunction with PET without the need of a near-by cyclotron.

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