| Popis: |
Background: Accurate staging is essential in the management of pancreatic and rectal adenocarcinomas, and where prognosis after management of advanced, unresectable disease remains poor, further treatment options are urgently needed. CXCR4 is the receptor for chemokine CXCL12, with enriched expression in malignant compared with normal tissue, and putative tumorigenic signalling functions. Pentixafor, a peptide targeting CXCR4, is a theranostic agent capable of being labelled with gallium-68 (Ga-68) for positron emission tomography (PET) imaging, and lutetium-177 (Lu-177) for therapy. Using PET scanning, we sought to explore the potential utility of pentixafor as a theranostic agent by examining avidity of Ga-68-pentixafor uptake in a pilot study of patients diagnosed with rectal or pancreatic ductal adenocarcinoma (PDAC).Methods: We performed a single-arm, prospective, single-institution pilot study. Patients with newly diagnosed pancreatic or rectal adenocarcinoma received Ga-68-pentixafor-PET in addition to the usual clinical and radiologic workup for their disease. Suitability for peptide receptor radionucleotide therapy (PRRT) was judged using the Thera-P trial criteria[1]. Using binomial probability, a target of 12 patients was set for recruitment for each cancer cohort, given that if more than seven patients demonstrated insufficient uptake, there would be 95% confidence that a sensitivity threshold which would be deemed to warrant further investigation in a larger study (85%) would not be met.Results: Pentixafor-PET was administered to 8 rectal cancer patients and 9 PDAC patients and no adverse events were noted. Low-to-moderate levels of pentixafor tracer avidity was demonstrated at all sites of primary disease, most sites of nodal metastatic disease and some distant metastases in each cohort, although less uptake relative to Fluorodeoxyglucose (FDG)-PET/CT was noted suggesting that use of pentixafor is inferior to FDG in staging. No patients satisfied PRRT suitability criteria and further recruitment was terminated.Conclusion: In this small pilot study, insufficient pentixafor avidity was demonstrated in cases of rectal cancer and PDAC to warrant further exploration as a potential candidate for radionuclide therapy.Trial registration: Australian New Zealand Clinical Trials Registry. ACTRN12617000596303 (rectal). ACTRN12617000595314 (pancreatic). Registered on 27th April 2017. https://www.anzctr.org.au/TrialSearch.aspx.First patient was enrolled on 2nd May 2017 |
