Association of [123I]I-PARPi SPECT/CT imaging and PARP immunohistochemical analysis in different cancers

Poly(Adenosine phosphate-ribose) polymerase inhibition is linked to improved outcomes in malignancies with homologous recombination deficiencies. However, despite the presence of homologous recombination deficiencies, inclusion of poly(Adenosine phosphate-ribose) polymerase inhibitor therapy does not translate to improved outcomes in some patients suggesting the need for complimentary patient selection tools. In this study, we present the biodistribution, uptake pattern and correlation of [ 123 I]I-PARPi with poly(Adenosine phosphate-ribose) polymerase immunohistochemistry as a potential complimentary tool for selecting patients for poly(Adenosine phosphate-ribose) polymerase inhibitor therapy. We prospectively evaluated eleven patients with cervical cancer(1), ovarian cancer(1), head and neck cancers(5), small cell neuroendocrine lung carcinoma(1) and breast cancer(3). SPECT/CT imaging was done 1-hour, 4-hours and 24-hours after intravenous injection of [ 123 I]I-PARPi. Whole-body planar imaging was done at 1-hour in some participants. Visual assessment of the images was done with uptake of [ 123 I]I-PARPi above the adjacent background regarded as positive. An association between the uptake on primary lesions with the findings on immunohistochemistry in archival primary lesion biopsy specimens was determined. Normal biodistribution was seen in the salivary glands, blood pool, bone marrow, liver, spleen, bowel and urinary system. 7-patients demonstrated primary lesion uptake of [ 123 I] I-PARPi, Positive lymph node uptake was seen in 4-patients with lymph node metastases. 10/11 patients demonstrated positive findings on immunohistochemistry. Overall, concordance between the SPECT/CT findings and immunohistochemical findings was seen in 6/11 patients. Amongst the 5-patients with discordant imaging findings and immunohistochemical findings 1-patient demonstrated positive SPECT/CT findings whereas the immunohistochemical findings showed no staining. The rest of the patients with discordant findings were negative on SPECT/CT and had weak positivity on immunohistochemistry. We report the diagnostic potential of [ 123 I]I-PARPi SPECT/CT in evaluating PARP overexpression in different tumours. We identified an association between PARP immunohistochemistry and PARP imaging with [ 123 I]I-PARPi, indicating that it is a non-invasive marker of PARP expression. Our findings suggest that [ 123 I]I-PARPi has promise as a screening tool for PARP inhibitors which warrants prospective, longitudinal, and multi-centre clinical studies.