Osteotropic cancer diagnosis by an osteocalcin inspired molecular imaging mimetic

Abstract

Background Although microcalcifications of hydroxyapatite can be found in both benign and malignant osteotropic tumors, they are mostly seen in proliferative lesions, including carcinoma. The aim of this present study is to develop a molecular imaging contrast agent for selective identification of hydroxyapatite calcification in human osteotropic tumor tissues ex vivo and in human osteosarcoma cells in vitro. Methods A bioinspired biomarker, hydroxyapatite binding peptide (HABP), was designed to mimic natural protein osteocalcin property in vivo. A fluorescein isothiocyanate dye conjugated HABP (HABP-19) was utilized to characterize hydroxyapatite on human osteotropic tumor tissue sections ex vivo and to selectively image hydroxyapatite calcifications in human osteosarcoma cells in vitro. Results Using a HABP-19 molecular imaging probe, we have shown that it is possible to selectively image hydroxyapatite calcifications in osteotropic cancers ex vivo and in human SaOS-2 osteosarcoma cells in vitro. Conclusion Hydroxyapatite calcifications were selectively detected in osteotropic tissues ex vivo and in the early stage of the calcification process of SaOS-2 human osteosarcoma in vitro using our HABP-19 molecular imaging probe. This new target-selective molecular imaging probe makes it possible to study the earliest events associated with hydroxyapatite deposition in various osteotropic cancers at the cellular and molecular levels. General significance It potentially could be used to diagnose and treat osteotropic cancer or to anchor therapeutic agents directing the local distribution of desired therapy at calcified sites.

P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging

“…These fluorophores were then tested in vitro for their ability to bind biologically relevant calcium salts, including hydroxyapatite (HA), calcium carbonate (CC), calcium phosphate (CP), calcium oxalate (CO), and calcium pyrophosphate (CPP) (Fig. 2 b) [ 39 ]. Among the five major calcium salts found in human body, HA is the major component and is also found in atherosclerotic plaques and bone neoplasms [ 40 ].…”

A novel peptide targets CD105 for tumour imaging in�vivo

“…The contrast of osteosarcoma images was enhanced by 170-230%. Other peptides, including the hydroxyapatite binding peptide, were used to characterise hydroxyapatite on human osteotropic tumour tissue (29). OSP-1 derived from the Ph.D.-12 Phage Display Peptide Library was able to specifically bind to 143B osteosarcomas, other than 293T human embryonic kidney cells.…”

Bidentate iminodiacetate modified dendrimer for bone imaging

“…It is also found in atherosclerotic plaques and osteotropic tumors, such as breast and prostate cancers. 20, 21 CaOx is present in tumors as well, but contrary to HA, it is found mostly in benign tumors. 21, 22 CaOx, together with calcium phosphate, is also the main component of nephrolithiasis.…”

“…20, 21 CaOx is present in tumors as well, but contrary to HA, it is found mostly in benign tumors. 21, 22 CaOx, together with calcium phosphate, is also the main component of nephrolithiasis. 23–25 Py is deposited in the joints in pathological conditions such as pseudogout.…”

“…Although all bones could be labeled, the highest signal was observed in bones located near growth plates, such as the femoral heads, lumbar vertebrae, and scapulae. Previously, we have used the osteocalcin mimic HABP-19 to demonstrate that the HA binding probes are useful not only for bone images but also for the diagnosis of pathological calcifications such as breast and arterial calcifications, which could be a sign of breast cancer 21 and atherosclerosis, 27 respectively. It is rational to postulate that IMPLD might have similar medical potential.…”