Toward Transpulmonary Chemoembolization with Degradable Starch Microspheres: Systematic Analysis of Local and Systemic Effects in a Porcine Model
To investigate local and systemic effects of transpulmonary chemoembolization (TPCE) with degradable starch microspheres (DSM) and doxorubicin. The long-term goal is to establish DSM-TPCE as a treatment option for pulmonary malignancies.
Materials and Methods
Nine pigs underwent TPCE of either the right or left lower lobe pulmonary artery (LLPA) and bland embolization (TPE) of the contralateral LLPA. Before the procedures, macroaggregated albumin (MAA) particles were injected into both LLPAs, to exclude systemic shunting. Pulmonary arterial pressure, heart rate and oxygenation were recorded immediately before and at 1, 3, 5 and 10 min after treatment.
To investigate possible nontarget embolization, animals underwent cerebral MRI (cMRI). We killed the animals after a contrast-enhanced chest computed tomography (CT) and performed a pathologic examination at 12 h (3), 24 h (3) and 72 h (3) after treatment.
All experiments were technically successful. Mean injected DSM dose until stasis was similar in TPCE and TPE (4.3 ± 1.4 vs. 4.0 ± 1.4 mL). Pulmonary arterial pressure increased significantly 3 min after treatment (TPE: 17 ± 5 vs. 27 ± 7 mmHg; TPCE: 22 ± 6 vs. 36 ± 8 mmHg). No significant changes in heart rate or peripheral oxygenation levels occurred. We observed no evidence of structural lung damage or permanent perfusion disruption on CT. MAA test injection and cMRI revealed no shunting or nontarget embolization. The pathologic assessment revealed nonspecific local inflammation of the lung parenchyma.
In this large-animal model, TPCE and TPE appear feasible and safe. We observed a mild increase in pulmonary arterial pressure. Nontarget embolization did not occur. TPCE, as well as TPE, did not cause structural damage to the normal lung parenchyma.
Part of this work was presented previously at CIRSE 2017 in Copenhagen (Cardiovasc Intervent Radiol (2017) 40(Suppl 2): 25. https://doi.org/10.1007/s00270-017-1725-y).
This study was funded by Pharmacept®. Design of the study and collection, analysis and interpretation of data as well as writing of the manuscript were solely performed by the above-mentioned authors.
Compliance with Ethical Standards
Conflicts of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
For this type of study, informed consent is not required.