The role of histopathological and biochemical parameters for predicting metastatic disease on 68 Ga-PSMA-11 PET in prostate cancer.

BACKGROUND: The aim of this study was to evaluate the role of histopathological and biochemical parameters in the prediction of the presence and number of PSMA positive lesions consistent with the metastatic spread of prostate cancer on 68 Ga-PSMA PET images. METHODS: Biochemical, histopathological and imaging data of 302 prostate cancer patients who underwent 68 Ga-PSMA-11 PET/CT or PET/MR imaging for primary staging were retrospectively analyzed. Patients were divided into two groups as "PET positive" and "PET negative" according to the presence of pathologic extraprostatic PSMA involvement. "PET positive" patients were additionally divided into two groups: oligometastatic (1-3 metastatic lesion) and multimetastatic (>3 metastatic lesions). RESULTS: The mean age of patients was 66.8 ± 7.6 years. Imaging modality was PET/MR in 223 (73.8%) and PET/CT in 79 (26.2%) of patients. Total PSA, PSA density (PSAD), ALP, and tumor ratio in biopsy specimens were found to be significantly higher in "PET positive" group compared to "PET negative" group and in multimetastatic group compared to oligometastatic group. PET positivity was observed in 3.8% of the low-intermediate risk groups (ISUP 1-3 and total PSA ≤ 20 ng/ml and PSAD < 0.15 ng/ml/cc). This ratio was 46% in the high-risk group (ISUP 4-5 or total PSA > 20 ng/ml or PSAD ≥ 0.15 ng/ml/cc) with a relative risk of 12 (p < .001). The prediction models to predict the PET positivity and the presence of distant metastasis had AUCs of 0.901 and 0.925, respectively; with ALP, total PSA, and tumor ratio in needle biopsy specimen as significant independent predictors (p < .05). CONCLUSIONS: In this study, 68 Ga-PSMA-11 PET positivity was significantly higher in the high-risk patient group than in the low-intermediate risk groups. The prediction models used for predicting the PET positivity and the presence of distant metastasis on PET imaging were successful with high discriminatory powers. In addition to total PSA and ISUP GG, ALP and tumor ratio in biopsy specimens can be used to identify high-risk patients.

Folate-based radiotracers for PET imaging--update and perspectives.

The folate receptor (FR) is expressed in many tumor types, among those ovarian and lung cancer. Due to the high FR affinity of folic acid, it has been used for targeting of FR-positive tumors, allowing specific delivery of attached probes to the malignant tissue. Therefore, nuclear imaging of FR-positive cancer is of clinical interest for selecting patients who could benefit from innovative therapy concepts based on FR-targeting. Positron emission computed tomography (PET) has become an established technique in clinical routine because it provides an increased spatial resolution and higher sensitivity compared to single photon emission computed tomography (SPECT). Therefore, it is of critical importance to develop folate radiotracers suitable for PET imaging. This review article updates on the design, preparation and pre-clinical investigation of folate derivatives for radiolabeling with radioisotopes for PET. Among those the most relevant radionuclides so far are fluorine-18 (t(1/2): 110 min, E(av) ß⁺: 250 keV) and gallium-68 (t(1/2): 68 min, E(av) ß⁺: 830 keV). Recent results obtained with new PET isotopes such as terbium-152 (t(1/2): 17.5 h, Eß⁺: 470 keV) or scandium-44 (t(1/2): 3.97 h, (Eav) ß⁺: 632 keV) are also presented and discussed. Current endeavors for clinical implementation of PET agents open new perspectives for identification of FR-positive malignancies in patients.