Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging

Abstract

Background: Understanding angiogenesis in prostate cancer is essential. LNCaP prostate xenograft tumors are androgen responsive and closely mimic clinical disease. Orthotopic animal models replicate aspects of the cancer microenvironment and are more clinically relevant than subcutaneous models.Comparative studies investigating angiogenesis using contrast-enhanced ultrasound (CEUS) imaging in subcutaneous and orthotopic mouse models of prostate cancer have not been performed.Methods: Tumor microcirculation and perfusion in subcutaneous and orthotopic LNCaP xenograft Balb/c athymic nude mice models were compared by investigating microbubble wash-in with CEUS. Results:The take rate of subcutaneous and orthotopic tumors were 58.3% and 68.2%, respectively.On CEUS, orthotopic prostate tumors enhanced more rapidly than subcutaneous tumors. Mean arrivaltime (Atm) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 4.21±1.86, 1.72±0.79, and 0.73±0.12 s, respectively. Mean Atm was significantly longer for subcutaneous tumors compared to orthotopic prostate tumors or kidney (P<0.01). Mean time to peak enhancement (TtoPk) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 38.56±13.23, 12.39±7.17, and 3.74±1.41 s, respectively. Mean TtoPk were significantly shorter for orthotopic prostate tumors and kidney compared to subcutaneous tumors (P<0.01). Mean wash-in area under the curve (WiAuC) for subcutaneous tumors, orthotopic

A Comparative Analysis of Orthotopic and Subcutaneous Pancreatic Tumour Models: Tumour Microenvironment and Drug Delivery

“…The MIP images of the subcutaneous tumours also demonstrated larger dark regions with no contrast agent, indicating necrotic areas. This was consistent with the large necrotic regions observed in the histological assessment, as seen in the other subcutaneous PDAC models [32]. The difference in the number of functional vessels and the perfusion might explain the difference in necrosis.…”

Nanoparticles Targeted to Fibroblast Activation Protein Outperform PSMA for MRI Delineation of Primary Prostate Tumors

“…Higher densities of vascular structures at the periphery of such orthotopic models have been previously demonstrated. [ 55 ]…”

“…Higher densities of vascular structures at the periphery of such orthotopic models have been previously demonstrated. [55] Finally, Prussian blue staining was performed to assess the distribution of iron oxide nanoparticles in the kidney, liver, and spleen in orthotopic tumor mice (Figure 7). Through visual assessment, there was no increase in Prussian blue staining in the spleen and kidneys in all nanoparticle groups when compared to the no particle control.…”

Efficient ultrasound-mediated drug delivery to orthotopic liver tumors – Direct comparison of doxorubicin-loaded nanobubbles and microbubbles

“…However, these models can differ immunologically and phenotypically from orthotopic models, where tumors naturally form (87,88). Subcutaneous tumors exhibit irregular vasculature with thin-walled vessels, while orthotopic tumors have more abundant vasculature with thicker walls, influencing drug delivery dynamics due to varying perfusion and hypoxia levels (89,90). Despite the prevalence of flank models, some researchers have explored MBs and NBs in orthotopic tumor models, recognized as optimal for studying therapeutic strategies (91)(92)(93)(94)(95).…”