# The Role of PET and SPECT Imaging in Prostate Cancer Targeted Alpha Therapy: When and How?
## 5 \({}^{225}\)Ac/\({}^{213}\)Bi-PSMA TAT
### Nuclear Medicine Imaging for Patients' Selection and Follow-Up after PSMA TAT
#### 5.1.2 \({}^{68}\)Ga-PSMA/\({}^{18}\)F-PSMA  
Interestingly, a recent consensus paper has recently been published by a multidisciplinary team of urologists, radiologists, and nuclear medicine physicians, reporting that PSMA PET imaging can be used at baseline and after local and systemic treatment in patients with metastatic disease, in order to evaluate the response to treatment. Ideally, PSMA PET/CT imaging criteria should categorize patients as responders (partial and complete response), patients with stable disease, or as non-responders, with a special consideration of specific clinical scenarios such as oligometastatic or poly-metastatic disease [86]. Beyond the specific therapy, the criteria to classify PSMA response into one of the four categories are the following [87]:  
* Complete response: Disappearance of any lesion with tracer uptake;
* Partial response: Reduction in uptake tumor PET volume by >30%;
* Stable disease: Change of uptake and tumor PET volume by \(\pm\leq\)30% and no new lesions documented;
* Progressive disease: Appearance of \(\geq\)2 new lesions or increase in uptake or tumor volume \(\geq\)30%. For the scope of the project, PSMA PET/CT refers to PET/CT imaging performed with several PSMA-targeting radiologists (e.g., \({}^{68}\)Ga-PSMA-11, \({}^{18}\)F-PSMA-1007, \({}^{18}\)F-DCFFyL) [86]. Concerning the different radio-compounds and isotopes used in PSMA-based TAT, \({}^{68}\)Gallium is a radioisotope with favorable pharmacokinetic characteristics with a commercial accessibility due to germanium-68/gallium-68 (Ge/Ga) generators and more recently produced by cyclotron, which allows a widespread diffusion [63]. In addition, in the PSMA field, the 68 Ga labeled tracers have been widely validated and used to define PSMA-positive lesions before 177 Lu-PSMA-617 in a previous study [88; 89]. Concerning the PSMA-based TAT monitoring, some recent studies indicate that \({}^{68}\)Ga-PSMA PET/CT could be a useful tool for the evaluation of response to \({}^{177}\)Lu-PSMA-617 radioligand therapy within a theranostic framework [90; 91] and that it could enhance RECIST criteria, specifically concerning its limitations for slcotic bone lesions [92]. \({}^{68}\)Ga-PSMA PET/CT may find greater application in response assessment of prostate cancer therapy, as it has already been shown to be a suitable replacement for conventional imaging, providing superior accuracy to the combined findings of CT and bone scanning in a randomized multicentric trial [93]. The optimal setting to use the PSMA-based TAT is still a matter of debate. Currently, PSMA-based TAT is performed in mCRPC non-responders to other treatments. In patients' selection, there should be adequate uptake on the PSMA ligand based on a diagnostic scan. Even if a clear protocol for eligibility has not been provided, some previous papers concerning beta-emitting-therapy describe the \({}^{68}\)Ga-PSMA uptake in lesions as a specific criterion, which should be 1.5\(\times\) higher than liver uptake [67; 94]. However, in the VISION trial, an international open-label phase 3 trial evaluating \({}^{177}\)Lu-PSMA-617 in mCRPC [89], the presence of PSMA-positive lesions was defined as \({}^{68}\)Ga-PSMA-11 uptake greater than that of liver parenchyma in one or more metastatic lesions of any size in any organ system. However, concerning the optimal setting for baseline assessment pre-treatment with \({}^{177}\)Lu-PSMA-617 in NCCCN Guidelines [95], the panel discussed the fact that the FDA-approved PSMA imaging agents--\({}^{68}\)Ga-PSMA-11 and \({}^{18}\)F-pifluofalast PSMA--share the same PSMA binding motif with each other and with \({}^{177}\)Lu-PSMA-617, suggesting that all approved PSMA PET imaging agents should be acceptable. Therefore, even if further clinical trials are needed, it seems reasonable to extend this assessment also to PSMA-based TAT. In fact, ongoing trials, described in Table 1, are using \({}^{68}\)Ga-PSMA as a diagnostic tool for PSMA-based TAT monitoring (NCT04597411, NCT04506567).