Chromosome aberrations of human small cell lung cancer induced by a new ¹¹¹in‐bleomycin complex

Abstract

A new 111Indium labeled bleomycin complex (111In‐BLMC) was prepared and found to be effective for tumor imaging and therapy both in mouse glioma and human small cell lung cancer (SCLC) cells. Chromosome aberrations were studied in human SCLC cells to explore its mechanisms of killing cancer cells. SCLC cells (N417) were exposed to 111In‐BLMC, BLM, or 111InCl3 (for control) for 1 hour, treated with colcemid, and chromosomal changes were analyzed. A dramatic increase in chromatic gaps, breaks, chromosome breaks, double minutes, rings, triradii, quadriradii, and chromosome stickiness were observed in the cells treated by 111In‐BLMC compared to BLM or 111InCl3. These results indicated that 111In‐BLMC has therapeutic potential for combination chemo‐radiotherapy of cancer (e.g., by Auger electrons and local energy deposition). © 1992 Wiley‐Liss, Inc.

Targeting the Nucleus: An Overview of Auger-Electron Radionuclide Therapy

“…In an autoradiography study by Hou and Maruyama, 78% of 111 In-BLMC was localised in the nucleus and nuclear membrane of human small cell lung cancer cells [117,118]. 111 In-BLMC induced more chromosome aberrations than BLMC [118,119]. The cytotoxicity of 111 In-BLMC has been demonstrated in human small cell lung cancer and head-and-neck carcinoma cell lines [120][121][122].…”

“…Given the increasing interest in the use of tRT in general and the use of Auger-electron-emitters in particular, more and more centres are now developing novel radiopharmaceuticals labelled with more potent Auger-electron-emitters, with more lowenergy electrons being emitted per decay. Some of the promising radioisotopes include 67 Ga [180], 119 Sb [184], 201 Tl, 165 Ho, 103m Rh [185, 186], 195m Hg [187], and 195m Pt [187]. The main challenge here is the implementation of new chemistries, to make the conjugation of these radionuclides possible.…”