Theranostic PET for Target Validation and Tumor Detection

Patients are referred for theranostic PET using different tracers as part of clinical routine for tumor staging, re-staging, and therapy planning to our department.

The aim of this study is to collect data on the expression of target molecules/receptors, proportion of PET positive tumor regions, positive predictive value, detection rate, reproducibility, and impact on clinical management of theranostic PET/CT or PET/MRI using novel theranostic PET tracers or other established PET tracers that are performed in theranostic concepts on patients receiving this imaging modality as part of clinical standard both at initial diagnosis and restaging before treatment decisions.

Primary Endpoint:

Association between PET uptake intensity in theranostic PET and histopathologic expression of the respective molecular target.

Secondary Endpoints:

1. Proportion of tumor manifestations with uptake in theranostic PET on a per-lesion, per-region, and per-patient basis 2. Detection rate and positive predictive value (PPV) of theranostic PET on a per-patient and per-region-basis for detection of tumor location, confirmed by histopathology/biopsy, clinical and conventional imaging follow-up (separate for regional, extra-regional and distant locations) 3. Sensitivity and specificity of theranostic PET on a per-patient and per-region-basis for detection of tumor location confirmed by histopathology/biopsy (separate for regional, extra-regional and distant locations) 4. Change in staging/prognostic groups and impact on clinical management 5. Inter-reader reproducibility 6. Detection rates of theranostic PET on a per-patient basis stratified by tumor maker serum level and velocity (if available) 7. Detection rate and PPV of theranostic PET (using different PET tracers) on a per-patient and per-region-basis stratified by PET tracer, tumor histology and involved organs

Hypothesis and expected outcome:

The PET signal (of the theranostic PET) correlates with expression levels of the respective molecular target. This can enable to discover novel imaging-based and clinical biomarkers Further, theranostic PET demonstrates high PPV and detection rate for tumor lesions, both locally and with distant metastases, compared to conventional morphological imaging, and it has the potential to be utilized for staging and restaging purposes for patients with various tumors. Moreover, expression of the respective target will enable therapeutic options in a relevant fraction of patients.

Inclusion criteria:

1. PET with a theranostic tracer (e.g., 68Ga-SSO120, 68Ga- DPI-4452, 68Ga-Pentixafor, 68Ga-DOTATOC, 68Ga-PSMA-11/18F-PSMA-1007, 68Ga-FAPI-46, 68Ga-NeoB or other PET tracer with theranostic potential) scheduled for staging or restaging of tumor types outlined in attached CRF #1 "Patient Screening and Diagnosis" as part of clinical routine 2. Age ≥ 18 years

Exclusion criteria:

1. Patient cannot give consent for the study 2. Patient cannot lie flat or tolerate PET imaging 3. Unwillingness or inability to comply with study and follow-up procedures 4. Condition of patient which is critical to participate in this study in the discretion of the investigators 5. Pregnant, lactating, or breast-feeding women

• Proportion of tumor manifestations with uptake in theranostic PET on a per-lesion, per-region, and per-patient basis [Time frame: 12 months]
• Detection rate and PPV of theranostic PET on a per-patient and per-region-basis, confirmed by histopathology, clinical and conventional imaging follow-up [Time frame: 12 months]
• Change in staging/prognostic groups and impact on clinical management [Time frame: 12 months]
• Inter-reader reproducibility [Time frame: 12 months]
• Detection rates of theranostic PET on a per-patient basis stratified by tumor maker serum level and velocity (if available) [Time frame: 12 months]
• Detection rate and PPV of theranostic PET (using different PET tracers) on a per- patient and per-region-basis stratified by PET tracer, tumor histology and involved organslevel and velocity (if available) [Time frame: 12 months]