Molecular Imaging of Angiogenesis in Oncology: Current Preclinical and Clinical Status

Abstract

Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status. After a structured PubMed search, the resulting publication list was screened for oncology related publications in animals and humans, disregarding any cardiovascular findings. The tracers identified can be subdivided into direct targeting of angiogenesis (i.e., vascular endothelial growth factor, laminin, and fibronectin) and indirect targeting (i.e., glucose metabolism, hypoxia, and matrix metallo-proteases, PSMA). Presenting pre-clinical and clinical data of most tracers proposed in the literature, the indirect targeting agents are not 1:1 correlated with angiogenesis factors but do have a strong prognostic power in a clinical setting, while direct targeting agents show most potential and specificity for assessing tumour vascularisation and vitality. Within the direct agents, the combination of multiple targeting tracers into one agent (multimers) seems most promising. This review demonstrates the present clinical applicability of indirect agents, but also the need for more extensive research in the field of direct targeting of angiogenesis in oncology. Although there is currently no direct tracer that can be singled out, the RGD tracer family seems to show the highest potential therefore we expect one of them to enter the clinical routine.

Molecular imaging of tumor-associated macrophages in cancer immunotherapy

“…The existing imaging techniques include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US), optica imaging, and emerging techniques such as hyperpolarized MRI, magnetic particle imaging (MPI), and photoacoustic imaging (PAI). 4 , 5 At present, molecular imaging technology is widely used in studies on oncology, 6 cardiovascular diseases, 7 and the nervous system 8 and has achieved some breakthroughs in disease diagnosis, treatment, and curative effect evaluations.…”

Comparison of a New 68Ga-Radiolabelled PET Imaging Agent sCD146 and RGD Peptide for In Vivo Evaluation of Angiogenesis in Mouse Model of Myocardial Infarction

“…68 Ga-sCD146 radiosynthesis: preparation of NODAGA-sCD146, its subsequent radiolabelling, the evaluation of radiolabelling stability and in vivo biodistribution were performed as previously described [ 6 ].…”

“…68 Ga-sCD146 radiosynthesis: preparation of NODAGA-sCD146, its subsequent radiolabelling, the evaluation of radiolabelling stability and in vivo biodistribution were performed as previously described [6]. 68 Ga-RGD 2 radiosynthesis: gallium-68 chloride ( 68 GaCl 3 , 200.7 ± 41 MBq/500 µL) was buffered with a fresh 2M ammonium acetate solution (pH 7.4) and 10 µg of RGD 2 precursor (catalogue number 9804, purchased at ABX, Radeberg, Germany) was added.…”

“…Positron emission tomography coupled with computed tomography (PET/CT) may represent an efficient and sensitive imaging modality to quantify angiogenesis, but the ideal molecular target and its associated radiotracer remain to be identified, developed and validated. Indeed, almost two decades after the first developments, PET imaging agents targeting integrins or molecules of the VEGF pathway still have not reached registration [ 6 ]. Several clinical studies in patients with MI and stroke showed an increased PET signal in the ischemic region in direct correlation with the phase and severity of the disease.…”

Pro-angiogenic approach for skeletal muscle regeneration

“…A fine balance between pro-angiogenic and anti-angiogenic factors allows a balanced progression of the vascular system. When this balance is broken, angiogenesis is altered leading to pathological states including inflammation, tumour, and restenosis [40][41][42] . Tumours and metastases depend on a regular blood supply and the balance between pro-angiogenic and anti-angiogenic factors shifted in favour of increased angiogenesis in this disease.…”