Solid malignancies can often not be cured by conventional chemo- and radiotherapy due to biological, but also biophysical factors of therapeutic resistance. Exponential tumor cell proliferation leads to areas of hypoxic focal necrosis with increased interstitial pressure gradients, causing capillary and venular collapse that blocks drug access to zones of rapid cell proliferation. In brain tumors, the blood brain barrier represents an additional obstacle for drugs to reach their target. This anatomical barrier can be overcome by local drug injection directly into the tumor mass. In this approach, drug distribution depends on the injection volume, injection velocity and injection resistance caused by elevated interstitial pressure. Physico-chemical properties of selected drugs also play a crucial role, since diffusion of a given drug is directly related to its molecular weight and its receptor-mediated haptic potency: small regulatory peptides and peptidomimetics are rapidly propagated throughout the extracellular space of the tumor following local injection while larger biomolecules display a reduced diffusive capacity. In addition, drug distribution can further be enhanced by flushing the port-catheter system with a prolonged micro-bulk flow following injection of 225Ac DOTA-substance P. Regarding malignant glial tumors of WHO grades II-IV, success of local therapy also critically depends upon correct stereotactic positioning of catheters. Following maximum debulking surgery (“supramaximal resection”), 225Ac DOTA-substance P is directly injected into the resection cavity through a port-catheter system. In many cases, critical tumor location in functionally sensitive areas obviates maximum debulking surgery. Therefore, tumor remnants of a diameter of > 2cm are left behind surgery with increased interstitial pressure hindering drug access. Even small drug-like vectors injected into the resection cavity cannot sufficiently penetrate these high pressure areas. Therefore, stereotactic insertion of at least one additional catheter into these bulky tumor remnants is mandatory to saturate the entire tumor system. Likewise, in neo-adjuvant TAT, 1-2 catheters have to be stereotactically inserted into the lesion.

MERLO A.;  KUNIKOWSKA Jolanta;  KROLICKI Leszek;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred; 

2026-05-05

ELSEVIER INC.

JRC145582

1876-7982 (online),   

https://www.sciencedirect.com/science/article/pii/S1939865426000718,    https://publications.jrc.ec.europa.eu/repository/handle/JRC145582,   

10.1016/j.jmir.2026.102257 (online),