Radioimmunotherapy of Pancreatic Ductal Adenocarcinoma: A Review of the Current Status of Literature

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has long been associated with low survival rates. A lack of accurate diagnostic tests and limited treatment options contribute to the poor prognosis of PDAC. Radioimmunotherapy using α- or β-emitting radionuclides has been identified as a potential treatment for PDAC. By harnessing the cytotoxicity of α or β particles, radioimmunotherapy may overcome the anatomic and physiological factors which traditionally make PDAC resistant to most conventional treatments. Appropriate selection of target receptors and the development of selective and cytotoxic radioimmunoconjugates are needed to achieve the desired results of radioimmunotherapy. The aim of this review is to examine the growing preclinical and clinical trial evidence regarding the application of α and β radioimmunotherapy for the treatment of PDAC. A systematic search of MEDLINE^® and Scopus databases was performed to identify 34 relevant studies conducted on α or β radioimmunotherapy of PDAC. Preclinical results demonstrated α and β radioimmunotherapy provided effective tumour control. Clinical studies were limited to investigating β radioimmunotherapy only. Phase I and II trials observed disease control rates of 11.2%-57.9%, with synergistic effects noted for combination therapies. Further developments and optimisation of treatment regimens are needed to improve the clinical relevance of α and β radioimmunotherapy in PDAC.

Keywords: alpha particles; beta particles; pancreatic cancer; radioimmunotherapy; radiolabelled antibodies; targeted therapy.

Figure A1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart demonstrating the process used to retrieve articles for this review.

Figure 1

The principles of radioimmunotherapy.

Figure 2

Distribution of publications of radioimmunotherapy (RIT) in pancreatic ductal adenocarcinoma (PDAC) by country of origin.

Figure 3

Cumulative distribution of identified publications RIT for PDAC since 2000.

Figure 4

Percentage of PDAC cell survival between RIT and control treatments. * Values estimated from graph. ** Average values used as necessary.

Figure 5

Median survival or time to end point for in vivo studies. A, stand-alone RIT (high and low doses) compared to control treatment (untreated or cold antibody). * p ≤ 0.01 and ** p ≤ 0.001 for high-dose RIT compared to control treatment. B, RIT in combination with other therapeutic agents (including pre-targeting) for the treatment of PDAC compared to untreated controls. * p < 0.05, ** p ≤ 0.001, *** p ≤ 0.0001 for combined therapy compared to control, except for Sharkey et al. [55] and Karacay et al. [56], where p-value compares combination therapy to stand-alone RIT. For Karacay et al. [56], the RIT only data point refers to PT-RIT only. A single representative case is used for studies where multiple experiments were conducted.

Figure 6

Overall median survival of PDAC patients in β RIT clinical trials.