Radioimmunotherapy of Solid Cancers: A review

Abstract

Depending on radionuclide characteristics, radioimmunotherapy (RIT) relies on radioactivity to destroy cells distant from immunotargeted cells. Therefore, even heterogeneous tumors (for antigen recognition) can be treated, because not all cells have to be targeted. Substantial complete response rates have been reported in patients with non-Hodgkin's lymphoma. Much more modest results have been reported for patients with bulky solid tumors, e.g. adenocarcinomas. The radiation doses delivered by targeting antibodies are generally too low to achieve major therapeutic responses. Dose escalation is limited by myelotoxicity, and higher doses need to be delivered to neoplasms less radiosensitive than lymphomas. Various trials for both systemic and regional RIT have been reported on. Intraperitoneal administration has been applied for colorectal and ovarian carcinomas. Our own results indicate that, e.g., intraperitoneal pseudomyxoma can be treated with RIT. Myelotoxicity can be reduced by anti-antibody-enhancement, 2- and 3-step strategies, bispecific monoclonal antibodies (MAbs), and extracorporeal immunoadsorption. The radionuclide has to be selected properly for each purpose; it can be a beta-emitter, e.g. I-131, Y-90, Re-188, Re-186, Lu-177 or Sm-153, an alpha-emitter At-211 or Bi-212 or an Auger-emitter, e.g. I-125, I-123. One major problem with RIT, besides slow penetration rate into tumor tissue and low tumor-to-normal tissue ratio, is the HAMA response, which can be partly avoided by the use of humanized MAbs and immunosuppression. However, RIT will be, because of all the recent developments, an important form of cancer management.

Targeting of meta-iodobenzylguanidine to SK-N-SH human neuroblastoma xenografts: Tissue distribution, metabolism and therapeutic efficacy

“…Our approach allows paired analysis of the radiation dose and response of individual tumors and accounts for treatment-induced size reductions. Many of the problems encountered in solid tumor dosimetry of systemic therapy with radiolabeled antibodies (Humm, 1996;Kairemo, 1996) also apply for targeted MIBG therapy as both involve the delivery of low dose-rate radiation by intratumoral radioactive sources. Important aspects of tumor dosimetry in radio-immunotherapy have been discussed in a series of comprehensive reviews collected in a special supplement issue of Medical Physics in 1993 (e.g., Buchsbaum et al, 1993;Langmuir et al, 1993;Leichner and Kwok, 1993;Meredith et al, 1993).…”

“…Presumably, in vivo dosimetry lacks sufficiently detailed information about the intra-tumoral [ 131 I]MIBG distribution. Spatial non-uniformity in source distributions is the largest unknown variable in systemic therapy with radiopharmaceuticals Humm, 1996;Kairemo, 1996), and imagebased macrodosimetry in xenografted mice thus shares shortcomings with that in humans because of limited resolution of the gamma camera, with an overall uncertainty of about 30 % (Humm, 1996).…”

13- and 14-membered macrocyclic ligands containing methylcarboxylate or methylphosphonate pendant arms: Chemical and biological evaluation of their 153Sm and 166Ho complexes as potential agents for therapy or bone pain palliation

“…153 Sm and 166 Ho complexes with tetraazamacrocycles linked to different biomolecules, such as monoclonal antibodies or peptides, have also been considered excellent candidates for therapy and are under investigation [16][17][18][19][20][21][22][23][24].…”

Improved Targeting of Pancreatic Cancer

“…Of particular note, specificity was demonstrated in that PAM4 did not target a case that was, in fact, active pancreatitis rather than pancreatic cancer. Radioimmunoscintigraphy of solid tumors has been hampered by the low, heterogeneous uptake of the antibodies in target tumors and by the long serum half-life of the labeled antibodies (74). Thus, signal:noise ratios are low for image processing.…”