Purpose To report the results of dual-time-point gallium 68 (Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUV]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation ofGa-PSMA-11 increased at later acquisition times, with higher mean SUV (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence,Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer’s safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin αvβ6.

Rationale: Novel radiopharmaceuticals for positron emission tomography (PET) are evaluated for the diagnosis of biochemically recurrent prostate cancer (BCR PC). Here, we compare the gastrin releasing peptide receptors (GRPR) -targeting 68 Ga-RM2 with the prostate specific membrane antigen (PSMA) -targeting 68 Ga-PSMA11 and 18 F-DCFPyL.Methods: Fifty patients had both 68 Ga-RM2 PET/MRI and 68 Ga-PSMA11 PET/CT (n=23) or 18 F-DCFPyL PET/CT (n=27) at an interval ranging from 1 to 60 days (mean±SD: 15.8±17.7).Maximum standardized uptake values (SUV max ) were collected for all lesions.Results: RM2 PET was positive in 35 and negative in 15 of the 50 patients. PSMA PET was positive in 37 and negative in 13 of the 50 patients. Both scans detected 70 lesions in 32 patients.Forty-three lesions in 18 patients were identified only on one scan: 68 Ga-RM2 detected 7 more lesions in 4 patients, while PSMA detected 36 more lesions in 13 patients.Conclusions: 68 Ga-RM2 remains a valuable radiopharmaceutical even when compared with the more widely used 68 Ga-PSMA11/ 18 F-DCFPyL in the evaluation of BCR PC. Larger studies are needed to verify that identifying patients for whom these two classes of radiopharmaceuticals are complementary may ultimately allow for personalized medicine.