Targeted Radiolabeled Compounds in Glioma Therapy

Malignant gliomas of WHO grades II-IV represent the largest entity within the group of intrinsic brain tumors and are graded according to their pathophysiologic features with survival times between more than 10 years (WHO II°) and only several months (WHO IV°). Gliomas arise from astrocytic or oligodendrocytic precursor cells and exhibit an infiltrative growth pattern lacking a clearly identifiable tumor border. The development of effective treatment strategies of the invasive tumor cell front represents the main challenge in glioma therapy. The therapeutic standard consists of surgical resection and, depending on the extent of resection and WHO grade, adjuvant external beam radiotherapy and/or systemic chemotherapy. Within the last decades, there has been no major improvement of the prognosis of glioma patients. The consistent overexpression of neurokinin type 1-receptors in gliomas WHO grades II-IV has been used to develop a therapeutic substance P-based targeting system. A substance P-analogue conjugated to the DOTA or DOTAGA chelator has been labelled with different alpha- or beta-particle emitting radionuclides for targeted glioma therapy. The radiopharmaceutical has been locally injected into the tumors or the resection cavity. In several clinical studies, the methodology has been examined in adjuvant and neoadjuvant clinical settings. Although no large controlled series have so far been generated, the results of radiolabelled substance P-based targeted glioma therapy compare favorably to standard therapy. Recently, labeling with the alpha particle-emitting Bi-213 has been found to be promising due to the high linear energy transfer and the very short tissue range of 0.08mm. Further development needs to focus on the improvement of the stability of the compound and the application by dedicated catheter systems to improve the intratumoral distribution of the radiopharmaceutical within the prognostically critical infiltrative growing zone of the glioma.

CORDIER D.;  KROLICKI Leszek;  MORGENSTERN Alfred;  MERLO A.; 

2016-06-22

W B SAUNDERS CO-ELSEVIER INC

JRC98415

0001-2998,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC98415,   

10.1053/j.semnuclmed.2016.01.009,