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

Abstract Background To evaluate whether 99m Tc-MIP-1404 CZT SPECT/CT is non-inferior to 68 Ga-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. Results Sensitivity of 99m Tc-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 99m Tc-HDP CZT SPECT/CT. There were no false positive findings by 99m Tc-MIP-1404 CZT SPECT/CT; specificity was 100% compared to 68 Ga-PSMA-11 PET/CE-CT. At lesion level analysis, 99m Tc-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 68 Ga-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 99m Tc-MIP-1404 CZT SPECT/CT compared to 68 Ga-PSMA-11 PET/CE-CT, while conventional imaging agreed in 64% of cases. Therapy decisions based on 99m Tc-MIP-1404 CZT SPECT/CT were concordant with those based on 68 Ga-PSMA-11 PET/CE-CT in 91% (30/33) of patients. Conclusions 99m Tc-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 68 Ga-PSMA-11 PET/CE-CT identified more additional lesions, concordance in treatment decisions remained high. Considering its broader accessibility, 99m Tc-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.