New challenges in integrated diagnosis by imaging and osteo-immunology in bone lesions

ABSTRACT

Introduction: High-resolution imaging is the gold standard to measure the functional and biological features of bone lesions. Imaging markers have allowed the characterization both of tumour heterogeneity and metabolic data. Besides, ongoing studies are evaluating a combined use of ‘imaging markers’, such as SUVs, MATV, TLG, ADC from PET and MRI techniques respectively, and several ‘biomarkers’ spanning from chemokine immune-modulators, such as PD-1, RANK/RANKL, CXCR4/CXCL12 to transcription factors, such as TP53, RB1, MDM2, RUNX family, EZH2, YY1, MAD2. Osteoimmunology may improve diagnosis and prognosis leading to precision medicine in bone lesion treatment.

Areas covered: We investigated modalities (molecular and imaging approach) useful to identify bone lesions deriving both from primary bone tumours and from osteotropic tumours, which have a higher incidence, prevalence and prognosis. Here, we summarized the recent advances in imaging techniques and osteoimmunology biomarkers which could play a pivotal role in personalized treatment.

Expert commentary: Although imaging and molecular integration could allow both early diagnosis and stratification of cancer prognosis, large scale clinical trials will be necessary to translate pilot studies in the current clinical setting.

Abbreviations: ADC: apparent diffusion coefficient; ALCAM: Activated Leukocyte Cell Adhesion Molecule; ALP: Alkaline phosphatases; BC: Breast cancer; BSAP: B-Cell Lineage Specific Activator; BSAP: bone-specific alkaline phosphatase; BSP: bone sialoprotein; CRIP1: cysteine-rich intestinal protein 1; CD44: cluster of differentiation 44; CT: computed tomography; CXCL12: C-X-C motif ligand 12; CXCR4: C-X-C C-X-C chemokine receptor type 4; CTLA-4: Cytotoxic T-lymphocyte antigen 4; CTX-1: C-terminal end of the telopeptide of type I collagen; DC: dendritic cell; DWI: Diffusion-weighted MR image; EMT: mesenchymal transition; ET-1: endothelin-1; FDA: Food and Drug Administration; FDG: ¹⁸F-2-fluoro-2-deoxy-D-glucose; FGF: fibroblast growth factor; FOXC2: forkhead box protein C2: HK-2: hexokinase-2; ICTP: carboxyterminal cross-linked telopeptide of type I collagen; IGF-1R: Insulin Like Growth Factor 1 Receptor; ILC: innate lymphocytes cells; LC: lung cancer; IL-1: interleukin-1; LYVE1: lymphatic vessel endothelial hyaluronic acid receptor 1; MAD2: mitotic arrest deficient 2; MATV: metabolically active tumour volume; M-CSF: macrophage colony stimulating factor; MM: multiple myeloma; MIP1a: macrophage inflammatory protein 1a; MSC: mesenchymal stem cell; MRI: magnetic resonance imaging; PC: prostate cancer; NRP2: neuropilin 2; OPG: osteoprotogerin; PDGF: platelet-derived growth factor; PD-1: Programmed Cell Death 1; PET: positron emission tomography; PINP: procollagen type I N propeptide; PROX1: prospero homeobox protein 1; PSA: Prostate-specific antigen; PTH: parathyroid hormone; RANK: Receptor activator of NF-kB ligand; RECK: Reversion-inducing-cysteine-rich protein; SEMAs: semaphorins; SPECT: single photon computed tomography; SUV: standard uptake value; TLG: total lesion glycolysis; TP53: tumour protein 53; VCAM-1: vascular endothelial molecule-1; VOI: volume of interest; YY1: Yin Yang 1.

KEYWORDS:

• Bone
• imaging
• marker
• osteoimmunology
• tumour

Article Highlights

• ‘Osteoimmunology’ attempts to understand the molecular interaction between bone tissue and immune system.

• Bone tumours and metastases alter bone homeostasis, resulting in reduced bone integrity and, consequently, increasing skeletal complications.

• Biochemical markers of bone metabolism may meet an unmet need for useful, noninvasive, and sensitive surrogate information for following patients’ skeletal health. Biochemical markers of bone metabolism are not yet an established surrogate endpoint for treatment efficacy.

• Several emergent markers of bone metabolism may prove to be useful prognostic indicators, including TP53, MDM2, RANKL, OPG and YY1.

• Imaging tools have deeply increased early detection of bone lesions.

• To overcome the limitations of conventional imaging procedures, hybrid-imaging techniques have emerged, like PET/CT and PET/MRI.

• In recent years, the study of ‘imaging markers’ is emerging.

• In order to increase diagnostic power and risk stratification of patients affected by bone primary and osteotropic tumours, an innovative approach could be correlate imaging features and molecular markers.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contributions

SC, DNF, NC had made substantial contributions to conception and design; SC, SA, DNF, NC had been involved in drafting the manuscript or revising it critically for important intellectual content; DNF, NC had given final approval of the version to be published.

Additional information

Funding

This work was supported by ‘Ricerca Finalizzata 2011–12 Grant’ (project code RF-2011–02349443) and ‘Ricerca Corrente 2017’ (project code RRC-2017) from Italian Ministry of Health.