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Purpose: To evaluate the performance of the Biograph Vision Quadra (Siemens Healthineers) PET/CT system. This new system is based on the Siemens Biograph Vision 600, using the same silicon photomultiplier-based detectors with 3.2��3.2��20-mm lutetium-oxoorthosilicate crystals. The Quadra's 32 detector rings provide a fourfold larger axial field of view (AFOV) of 106 cm, enabling imaging of major organs in one bed position. Methods: Physical performance of the scanner was evaluated according to the National Electrical Manufacturers Association NU 2-2018 standard with additional experiments to characterize energy resolution. Image quality was assessed with foreground to background ratios of 4:1 and 8:1. Additionally, a clinical 18F-FDG-PET study was reconstructed with varying frame durations. In all experiments, data were acquired using the Quadra's maximum ring distance of 322 crystals (MRD 322), while image reconstructions could only be performed with a maximum ring distance of 85 crystals rings (MRD 85). Results: The spatial resolution at full width half maximum in radial, tangential and axial directions were 3.3, 3.4 and 3.8 mm respectively. The sensitivity was 83 cps/kBq for MRD 85 and 176 cps/kBq for MRD 322. The NECRs at peak were 1613 kcps for MRD 85 and 2956 kcps for MRD 322, both at 27.5 kBq/mL. The respective scatter fractions at peak NECR equaled 36 % and 37 %. The TOF resolution at peak NECR was 228 ps for MRD 85 and 230 ps for MRD 322. Image contrast recovery ranged from 69.6% to 86.9 % for 4:1 contrast ratios and from 77.7 % to 92.6 % for 8:1 contrast ratios reconstructed using PSF-TOF with 8 iterations and 5 subsets. Thirty seconds frames provided readable lesion detectability and acceptable noise levels in clinical images. Conclusion: The Biograph Vision Quadra PET/CT has similar spatial and time resolution compared to the Biograph Vision 600 but exhibits improved sensitivity and NECR due to its extended AFOV. The reported spatial resolution, time resolution, and sensitivity makes it a competitive new device in the class of PET-scanners with extended AFOV.

The objective of this study was to evaluate the rate of detection of bone metastases obtained with the prostate-specific membrane antigen (PSMA)-targeting tracer 99mTc-MIP-1427, as opposed to conventional bone scanning with 99mTc-methylene diphosphonate (99mTc-MDP), in a collective of patients with known advanced-stage osseous metastasized prostate cancer. Methods: Twenty-one patients with known metastatic disease were staged with both conventional bone scanning and PSMA ligand scintigraphy within a time frame of less than 10 d. Imaging included planar whole-body scanning and SPECT or SPECT/CT with 2 bed positions 3 h after injection of either 500-750 MBq of 99mTc-MIP-1427 or 600-750 MBq of 99mTc-MDP. Lesions were scored as typical tumor, equivocal (benign/malignant), or normal within a standard reporting schema divided into defined anatomic regions. Masked and consensus readings were performed with sequential unmasking: planar scans first, then SPECT/CT, the best evaluable comparator (including MRI), PET/CT, and follow-up examinations. Results: Eleven patients had PSMA-positive visceral metastases that were predictably not diagnosed with conventional bone scanning. However, SPECT/CT was required to distinguish between soft-tissue uptake and overlapping bone. Four patients had extensive 99mTc-MDP-negative bone marrow lesions. Seven patients had superscan characteristics on bone scans; in contrast, the extent of red marrow involvement was more evident on PSMA scans. Only 3 patients had equivalent results on bone scans and PSMA scans. In 16 patients, more suspect lesions were detected with PSMA scanning than with bone scanning. In 2 patients (10%), a PSMA-negative tumor phenotype was present. Conclusion: PSMA scanning provided a clear advantage over bone scanning by reducing the number of equivocal findings in most patients. SPECT/CT was pivotal for differentiating bone metastases from extraosseous tumor lesions.

Although PET/CT with 68Ga-PSMA-11 in the diagnosis of prostate cancer (PCa) is routinely performed at 1 h after injection, later scans may be beneficial because most lesions present with higher uptake and contrast. This evaluation aimed to investigate the clinical impact of additional late 68Ga-PSMA-11 PET/CT. Methods: Between 2011 and 2016, 112 patients with PCa who underwent early (at 1 h after injection) and late (at 3 h after injection) 68Ga-PSMA-11 PET/CT scans were retrospectively evaluated. The late scans were conducted to clarify unclear findings in early scans or to increase the probability of tumor detection in the case of negative early scans. All patients were asked to drink 1 L of water between early and late scans. In addition, 20 patients received 20 mg of furosemide before late scans. Tumor detection and radioactivity concentration within the urinary bladder were analyzed in both scans. The SUVmax and contrast of 149 tumor lesions were measured in 69 patients with pathologic findings. Results: Overall, 134 lesions characteristic for PCa in 57 patients clearly presented at 1 h after injection and 147 lesions in 68 patients at 3 h after injection. Forty-three patients showed no pathologic findings. Eight patients (7.1%) showed 1 unclear finding in early scans, which could be clarified as characteristic for PCa at 3 h after injection. Four patients (3.6%) presented with 1 lesion characteristic for PCa at 3 h after injection only. Twelve patients (10.7%) presented with 12 possible PCa lesions at 1 h after injection, which, however, could not be confirmed as PCa in late scans. Two patients presented with 1 lesion characteristic for PCa at 1 h after injection, which became invisible at 3 h after injection because of low contrast. At 3 h after injection, 62.4% of the lesions demonstrated a higher SUVmax and 65.1% a higher contrast than at 1 h after injection. Patients with furosemide presented with lower SUV and radioactivity concentration within the urinary bladder. Conclusion:68Ga-PSMA-11 PET/CT at 3 h after injection showed most lesions characteristic for PCa with a higher uptake and contrast. In addition, the radioactivity signal within the urinary bladder was lower at 3 h after injection, especially when furosemide was applied. Consequently, scans at 3 h after injection detected more tumor lesions than at 1 h after injection.

The prostate-specific membrane antigen (PSMA) has received increased consideration during the past few years as an excellent target for both imaging and therapy of prostate cancer. After many years of outstanding preclinical research, the first significant step forward in clinical use was achieved in 2008 with the first human experience with the small-molecule PSMA inhibitors 123I-MIP-1972 and 123I-MIP-1095. A clinical breakthrough followed in 2011 with 68Ga-PSMA-11 for PET imaging and 131I-MIP-1095 for endoradiotherapy of metastatic prostate cancer. Since then, PET/CT with 68Ga-PSMA-11 has rapidly spread worldwide, and endoradiotherapy with PSMA ligands has been conducted at increasing numbers of centers. 68Ga-PSMA-11 is currently the subject of multicenter studies in different countries. Since 2013, 131I-related PSMA therapy has been replaced by 177Lu-labeled ligands, such as PSMA-617, which is also the subject of multicenter studies. Alternative PSMA ligands for both imaging and therapy are available. Among them is 99mTc-MIP-1404, which has recently entered a phase 3 clinical trial. This article focuses on the highlights of the development and clinical application of PSMA ligands.

The purpose of this work was to evaluate the effect of androgen receptor (AR) inhibition on prostate-specific membrane antigen (PSMA) uptake imaged using 68Ga-PSMA-11 PET in a mouse xenograft model and in a patient with castration-sensitive prostate cancer. Methods: We imaged 3 groups of 4 mice bearing LNCaP-AR xenografts before and 7 d after treatment with ARN-509, orchiectomy, or control vehicle. Additionally, we imaged one patient with castration-sensitive prostate cancer before and 4 wk after treatment with androgen deprivation therapy (ADT). Uptake on pre- and posttreatment imaging was measured and compared. Results: PSMA uptake increased 1.5- to 2.0-fold in the xenograft mouse model after treatment with both orchiectomy and ARN-509 but not with vehicle. Patient imaging demonstrated a 7-fold increase in PSMA uptake after the initiation of ADT. Thirteen of 22 lesions in the imaged patient were visualized on PSMA PET only after treatment with ADT. Conclusion: Inhibition of the AR can increase PSMA expression in prostate cancer metastases and increase the number of lesions visualized using PSMA PET. The effect seen in cell and animal models can be recapitulated in humans. A better understanding of the temporal changes in PSMA expression is needed to leverage this effect for both improved diagnosis and improved therapy.

Despite many advances in the past years, the treatment of metastatic prostate cancer still remains challenging. In recent years, prostate-specific membrane antigen (PSMA) inhibitors were intensively studied to develop low-molecular-weight ligands for imaging prostate cancer lesions by PET or SPECT. However, the endoradiotherapeutic use of these compounds requires optimization with regard to the radionuclide-chelating agent and the linker moiety between chelator and pharmacophore, which influence the overall pharmacokinetic properties of the resulting radioligand. In an effort to realize both detection and optimal treatment of prostate cancer, a tailor-made novel naphthyl-containing DOTA-conjugated PSMA inhibitor has been developed. Methods: The peptidomimetic structure was synthesized by solid-phase peptide chemistry and characterized using reversed-phase high-performance liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry. Subsequent 67/68Ga and 177Lu labeling resulted in radiochemical yields of greater than 97% or greater than 99%, respectively. Competitive binding and internalization experiments were performed using the PSMA-positive LNCaP cell line. The in vivo biodistribution and dynamic small-animal PET imaging studies were investigated in BALB/c nu/nu mice bearing LNCaP xenografts. Results: The chemically modified PSMA inhibitor PSMA-617 demonstrated high radiolytic stability for at least 72 h. A high inhibition potency (equilibrium dissociation constant [Ki] = 2.34 ± 2.94 nM on LNCaP; Ki = 0.37 ± 0.21 nM enzymatically determined) and highly efficient internalization into LNCaP cells were demonstrated. The small-animal PET measurements showed high tumor-to-background contrasts as early as 1 h after injection. Organ distribution revealed specific uptake in LNCaP tumors and in the kidneys 1 h after injection. With regard to therapeutic use, the compound exhibited a rapid clearance from the kidneys from 113.3 ± 24.4 at 1 h to 2.13 ± 1.36 percentage injected dose per gram at 24 h. The favorable pharmacokinetics of the molecule led to tumor-to-background ratios of 1,058 (tumor to blood) and 529 (tumor to muscle), respectively, 24 h after injection. Conclusion: The tailor-made DOTA-conjugated PSMA inhibitor PSMA-617 presented here is sustainably refined and advanced with respect to its tumor-targeting and pharmacokinetic properties by systematic chemical modification of the linker region. Therefore, this radiotracer is suitable for a first-in-human theranostic application and may help to improve the clinical management of prostate cancer in the future.