Head-to-head comparison of <sup>99m</sup>Tc-MIP-1404 CZT SPECT/CT and <sup>68</sup>Ga/PSMA-11 PET/CT for primary staging of high-risk prostate cancer: a phase II study.

Abstract

BackgroundTo evaluate whether 99mTc-MIP-1404 CZT SPECT/CT is non-inferior to 68Ga-PSMA-11 PET/CT for metastases detection in patients with newly diagnosed high risk prostate cancer (PCa). Patients with newly diagnosed high-risk PCa (age range 50-79 years, mean 66) underwent three imaging modalities: 99mTc-HDP CZT SPECT/CT, 68Ga-PSMA-11 PET/CE-CT (contrast-enhanced CT), and 99mTc-MIP-1404 CZT SPECT/CT. Metastatic involvement of lymph nodes (LN) and bones were recorded. Repeated-measures ANOVAs and post-hoc analyses were used to compare modality performance. Sensitivity and specificity for LN and skeletal lesions were calculated based on PET scans as the reference standard. 99mTc-MIP-1404 CZT SPECT/CT-based therapy decisions were compared to 68Ga-PSMA-11 PET/CT-based decisions.ResultsSensitivity of 99mTc-MIP-1404 CZT SPECT/CT for metastasis detection at the patient level was 81% for LN metastasis and 85% for bone metastases, compared with 57% for bone metastases by 99mTc-HDP CZT SPECT/CT. There were no false positive findings by 99mTc-MIP-1404 CZT SPECT/CT; specificity was 100% compared to 68Ga-PSMA-11 PET/CE-CT. At lesion level analysis, 99mTc-MIP-1404 CZT SPECT/CT had significantly higher detection rate of LN metastases compared with CE-CT (p = 0.026), but a lower detection rate compared to 68Ga-PSMA-11 PET/CE-CT (p = 0.003). Classification of metastasis burden into high volume metastasis (HVM) and low volume metastasis (LVM) was concordant in 85% of cases based on 99mTc-MIP-1404 CZT SPECT/CT compared to 68Ga-PSMA-11 PET/CE-CT, while conventional imaging agreed in 64% of cases. Therapy decisions based on 99mTc-MIP-1404 CZT SPECT/CT were concordant with those based on 68Ga-PSMA-11 PET/CE-CT in 91% (30/33) of patients.Conclusions99mTc-MIP-1404 CZT SPECT/CT demonstrates strong diagnostic capability for metastatic staging and therapy planning in newly diagnosed high-risk PCa, outperforming conventional imaging. While 68Ga-PSMA-11 PET/CE-CT identified more additional lesions, concordance in treatment decisions remained high. Considering its broader accessibility, 99mTc-MIP-1404 CZT SPECT/CT may represent a practical alternative for primary staging, especially in settings with limited PET/CT availability. The study was approved by the Swedish Ethical Review Authority (approval number 2021 - 01642) and the Swedish Medical Products Agency (EudraCT-number 2021-001059-15). Trial registration date 16th February 2022.