Abstract
Radiohybrid PSMA (rhPSMA) ligands, a new class of theranostic prostate-specific membrane antigen (PSMA)–targeting agents, feature fast 18F synthesis and utility for labeling with radiometals. Here, we assessed the biodistribution and image quality of 18F-rhPSMA-7 to determine the best imaging time point for patients with prostate cancer. Methods: In total, 202 prostate cancer patients who underwent a clinically indicated 18F-rhPSMA-7 PET/CT were retrospectively analyzed, and 12 groups based on the administered activity and uptake time of PET scanning were created: 3 administered activities (low, 222–296 MBq; moderate, 297–370 MBq; and high, 371–444 MBq) and 4 uptake time points (short, 50–70 min; intermediate, 71–90 min; long, 91–110 min; and extra long, ≥111 min). For quantitative analyses, SUVmean and organ- or tumor-to-background ratio were determined for background, healthy organs, and 3 representative tumor lesions. Qualitative analyses assessed overall image quality, nonspecific blood-pool activity, and background uptake in bone or marrow using 3- or 4-point scales. Results: In quantitative analyses, SUVmean showed a significant decrease in the blood pool and lungs and an increase in the kidneys, bladder, and bones as the uptake time increased. SUVmean showed a trend to increase in the blood pool and bones as the administered activity increased. However, no significant differences were found in 377 tumor lesions with respect to the administered activity or uptake time. In qualitative analyses, the overall image quality was stable along with the uptake time, but the proportion rated to have good image quality decreased as the administered activity increased. All other qualitative image parameters showed no significant differences for the administered activities, but they showed significant trends with increasing uptake time: less nonspecific blood activity, more frequent background uptake in the bone marrow, and increased negative impact on clinical decision making. Conclusion: The biodistribution of 18F-rhPSMA-7 was similar to that of established PSMA ligands, and tumor uptake of 18F-rhPSMA-7 was stable across the administered activities and uptake times. An early imaging time point (50–70 min) is recommended for 18F-rhPSMA-7 PET/CT to achieve the highest overall image quality.
Prostate-specific membrane antigen (PSMA)–targeting ligands have been extensively investigated for molecular imaging and radioligand therapy of prostate cancer. Among these ligands, 68Ga labeled with Glu-NH-CO-NH-Lys-(Ahx) (68Ga-PSMA-11) is most widely used in clinical settings. However, 68Ga-PSMA-11 is rapidly excreted via the urinary tract, resulting in intense accumulation in the urinary bladder.
18F-based PET is preferred to 68Ga-based PET because of ease of production as well as better handling and image resolution. The shorter half-life of 68Ga often limits clinical availability compared with 18F, because distribution of 68Ga-based PET agents from a central facility to local imaging centers is infeasible. The limited size of a 68Ge/68Ga generator results in a quantity of activity suitable for only 2–4 patients. Moreover, operating the 68Ge/68Ga generator becomes less economical in local imaging centers because of its high price and relatively low productivity. Lastly, 68Ga has a higher positron energy than 18F, which reduces the theoretic maximum spatial resolution (1). Consequently, the unique characteristics of 18F, which include a relatively longer half-life and shorter positron energy, and the possibility of its large-scale production from cyclotrons have encouraged the development of 18F-based PSMA ligands for clinical prostate cancer imaging.
Several research groups have focused on the development of 18F-based PSMA ligands. The first of its generation, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-18F-fluorobenzyl-l-cysteine (18F-DCFBC), demonstrated feasibility and potential to detect metastatic prostate cancer with a radiation dose comparable to that of 18F-FDG in the first human study (2). However, 18F-DCFBC has high affinity for plasma protein, which produces slow clearance kinetics and high blood-pool activity that can interfere with the detection of lower avidity or smaller tumors (3,4). In contrast, 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) showed 5 times higher PSMA affinity, better tumor uptake, and more rapid plasma clearance than 18F-DCFBC, resulting in higher tumor-to-blood and tumor-to-background ratios and lower accumulation in the liver (5). However, considerable kidney and salivary gland uptake still persisted in PET/CT with 18F-DCFPyL (5). Furthermore, neither 18F-DCFBC nor 18F-DCFPyL includes a chelator capable of use for theranostic applications. In this regard, novel 18F-based PSMA ligands, such as 18F-PSMA-1007, were designed to have a radiochemical structure similar to PSMA-617, since PSMA-617 is a commonly used PSMA ligand for radioligand therapy. 18F-PSMA-1007 exhibits an excellent sensitivity for the detection of small metastatic lymph nodes and showed predominant hepatobiliary excretion with reduced urinary retention of the tracer in the first human study (6). However, favorable tumor-to-background ratios can be acquired only at late imaging time points, that is, 3 h after injection, as 18F-PSMA-1007 shares the slower tracer kinetics of PSMA-617 (6).
Radiohybrid PSMA ligands (rhPSMA) make up a new class of theranostic PSMA-targeting agents that allow fast radiolabeling with 18F and radiometals. 18F-rhPSMA-7 is the lead compound of this class and can be produced in high quantities relatively easily. Here, we assessed the biodistribution and image quality of 18F-rhPSMA-7 to determine the optimal imaging time point.
MATERIALS AND METHODS
Patients
In a first step, all patients with histopathologically proven prostate cancer who underwent a clinically indicated 18F-rhPSMA-7 PET/CT scan between October 2017 and June 2018 were collected from the institution’s database. The administered activity was based on the patient’s body weight (∼4 MBq/kg). On the basis of experience with other 18F-labeled PSMA ligands, an uptake time window of 1–2.5 h was defined. The specific uptake time for each patient was dependent on the logistics of the PET unit.
In a second step, 202 patients (mean age, 72.5 y; range, 49–91 y) were retrospectively selected and sorted into groups according to administered activity and uptake time. Twelve groups with a maximum of 20 patients each were established on the basis of both administered activity (3 groups: low, 222–296 MBq; moderate, 297–370 MBq; and high, 371–444 MBq) and uptake time (4 groups: short, 50–70 min; intermediate, 71–90 min; long, 91–110 min; and extra long, ≥111 min). Patients were stratified into the groups based on prostate-specific antigen (PSA) value and indication, to adjust for similar tumor stages. These patients were injected with a mean 18F-rhPSMA-7 activity of 330 MBq (range, 232–424 MBq). PET/CT scanning was started on average 85 min after injection of 18F-rhPSMA-7 (range, 58–153 min).
Clinical indications for 18F-rhPSMA-7 PET/CT scanning were tumor recurrence for 145 patients and primary staging for 57 patients. The mean PSA level at the time of PET/CT scanning was 11.6 ng/mL (range, 0.1–95.3 ng/mL). The primary therapy for tumor recurrence was radical prostatectomy in 129 patients and external-beam radiation therapy in 16 patients; 42 patients received androgen deprivation therapy at the time of the PSMA-ligand PET scan or within 6 mo beforehand.
All patients gave written informed consent for the procedure. All reported investigations were conducted in accordance with the Helsinki Declaration and with national regulations. The retrospective analysis was approved by the Local Ethics Committee (permit 290/18S). Administration of 18F-rhPSMA-7 was in accordance with the German Medicinal Products Act (AMG §13 2b) and the responsible regulatory body (government of Oberbayern). Table 1 summarizes the administered activities, uptake times, and clinical indications for the patient population. Synthesis of 18F-rhPSMA-7 was performed as described previously (7). The patients received an injection of 20 mg of furosemide at the time of tracer application. To avoid potential interference from tracer retention in the urinary bladder, all patients were asked to void immediately before the PET/CT acquisition.
Stratification of Patients into Different Groups Based on Administered Activity and Acquisition Time
PET/CT Imaging
PET/CT imaging was performed from the base of the skull to the mid thigh, using a Biograph mCT flow scanner (Siemens Medical Solutions). All PET scans were acquired in 3-dimensional mode with an acquisition time of 1.1 mm/s in continuous table movement (the equivalent of 2 min per bed position in traditional mode). The acquired PET data were corrected and reconstructed iteratively by an ordered-subsets expectation maximization algorithm (4 iterations, 8 subsets) followed by a postreconstruction smoothing gaussian filter (5 mm in full width at half maximum). A diagnostic CT scan (240 mAs, 120 kV, 5-mm slice thickness) was performed in the portal venous phase 80 s after the intravenous injection of an iodinated contrast agent (iomeprol [Iomeron 300; Bracco], at 1.5 mL/kg of body weight; maximum, 120 mL).
Image Analysis
All quantitative and qualitative analyses were performed using non–time-of-flight/non-True X (Siemens) PET datasets. Quantitative analyses were conducted using OsiriX MD (Pixmeo SARL) with reformation into axial, coronal, and sagittal views. For evaluation of the biodistribution, circular volumes of interest with diameters of 20–30 mm were placed over the normal organs: parotid gland, submandibular gland, mediastinal aortic arch (blood pool), lungs, liver, spleen, pancreas, duodenum, kidneys, bladder, sacral promontory, and gluteus maximus muscle (background). For evaluation of tumor lesions, circular volumes of interest with diameters of 15 mm were placed for 3 lesions per patient in decreasing order of the SUVmax. Volume-of-interest placement and image analyses were performed by a board-certified nuclear medicine physician. SUVmax and SUVmean were measured. SUVmean was calculated using an isocontour of 50% of the SUVmax. Organ- and tumor-to-background ratios for SUV and SUVmax were calculated.
Qualitative image analyses were performed by a different board-certified nuclear medicine physician who was masked to the injected activity and the uptake time. The overall image quality, nonspecific blood-pool activity, and background uptake in bone or marrow were evaluated using 3- or 4-point scales. Details on the grading system are presented in Table 2.
Grading Systems for Qualitative Image Analyses
Statistical Analysis
For the analyses of continuous variables, the Kolmogorov–Smirnov test was used to assess the normality of the distribution. A 1-way ANOVA test was applied to compare means among groups for the normal parameters. If the ANOVA F statistic was significant, a post hoc pairwise comparison using a t test was conducted with Bonferroni adjustment. Before the ANOVA test, A Levene test was performed to test the homogeneity of variances across groups. The Welch robust ANOVA F test was performed when violating the assumption of homogeneous variances, and the Tamhane T2 test was considered for the post hoc group comparisons. Likewise, the Kruskal–Wallis test was performed for the nonnormal parameters. If that test was significant, a Mann–Whitney U test was conducted with Bonferroni adjustment for the pairwise comparisons. In addition, to evaluate trends across groups on parameters of interest, a linear-contrast test was performed for the normal parameters and a Jonckheere–Terpstra test was conducted for the nonnormal parameters. Supplemental Figure 1 shows the workflow for these statistical analyses (supplemental materials are available at http://jnm.snmjournals.org).
For the analyses of ordinal variables, the χ2 test or the Fisher exact test was adopted to compare differences among groups, and the Mantel–Haenszel test was added to identify linear association among variables.
Data are expressed as mean ± SD and percentages for continuous and categoric variables, respectively. All statistical analyses were performed using the SPSS Statistics (version 25; IBM Inc.) and R (version 3.5.2). P values of less than 0.05 were considered statistically significant.
RESULTS
Quantitative Biodistribution
The biodistribution of 18F-rhPSMA-7 was similar to that of established PSMA ligands. High levels of radiotracer uptake were observed in the salivary glands, liver, spleen, duodenum, kidneys, and urinary bladder. In contrast, uptake in the background, mediastinal blood pool, and lungs was minimal. Tracer retention was relatively low in the bladder. Physiologic uptake in bones was also low compared with other normal organs. Figure 1 shows the maximum-intensity-projection image of a patient with a normal biodistribution for 18F-rhPSMA-7. Figure 2 summarizes the SUVmean and the SUVmean ratio in normal organs.
18F-rhPSMA7 biodistribution: maximum-intensity-projection image illustrating tracer accumulation in salivary glands, liver, spleen, pancreas, bowel, kidneys, and bladder at 1 h after injection. Focal uptake (arrow) near bladder indicates lesion in prostate.
Bar graphs displaying normal distribution according to SUVmean (A) and SUVmean ratio (B). These graphs display biodistribution for entire patient cohort regardless of uptake time, and error bars show 95% confidence intervals for mean (data represent all patients analyzed, including all uptake times and administered activities).
Biodistribution among healthy organs varied slightly with administered activity and uptake time. Data for differences and trends of means are presented in Tables 3 and 4. Background uptake was low and relatively stable across all administered activities and uptake times. Background SUVmean showed statistically significant trends toward an increase with increasing administered activity and a decrease with increasing uptake time. However, the absolute differences were low (Tables 3 and 4).
Quantitative Assessment of Biodistribution for Different Administered Activities
Quantitative Assessment of Biodistribution for Different Uptake Times
SUVmean in the blood pool, lungs, kidneys, bladder, and bones revealed further significant trends for different activities and uptake times. With increasing administered activity, SUVmean increased in these organs (Table 3). With increasing uptake time, SUVmean decreased in the blood pool and lungs and increased in the kidneys, bladder, and bones (Table 4). Figure 3 summarizes the differences in means and trends for SUVmean of the blood pool, bone, kidney, and bladder for different uptake times.
Changes in SUVmean ratio according to uptake time. Increase in uptake time leads to decrease in retention in blood pool but increase in accumulation in normal bone, kidneys, and urinary bladder. x-axis gives different uptake time groups (group 1, 50–70 min; group 2, 71–90 min; group 3, 91–110 min; group 4, ≥ 111 min). A, C, and D show significant trends; B (bone) has P value of 0.052.
Quantitative Evaluation of Tumor Lesions
In 187 of 202 patients included in the analyses, 377 tumor lesions were present in the PET scan (Table 1). Of 2 visceral lesions, one was in the lung and the other in the right testicle. Because of the low number of visceral lesions, they were excluded from the final statistical analyses. Supplemental Table 1 summarizes SUVmean for tumor lesions according to tumor location, administered activity, and uptake time. SUVmean for tumor lesions showed no clear differences with respect to administered activity or uptake time. When bone lesions were compared with all other soft-tissue lesions, they showed a significantly higher SUVmean (15.63 ± 14.15 vs. 10.58 ± 19.28, P < 0.001) and SUVmean ratio (28.59 ± 24.24 vs. 19.93 ± 20.24, P < 0.001).
Qualitative Image Analyses
The qualitative image analyses showed different patterns according to the administered activity and uptake time. Data for differences and trends of means are presented in Table 5. The overall image quality was stable for the different uptake times. With increasing administered activity, a trend toward decreasing overall image quality was noted. For example, the percentage of imaging datasets rated best (rating 1) decreased (P < 0.001).
Qualitative Analyses of Image Quality
For all other qualitative image parameters, there were no notable variations across the range of administered activity. In contrast, a significant trend toward less nonspecific blood activity (P = 0.014) and higher uptake in the bone marrow (P = 0.011) was observed with increasing time. Although nonspecific blood-pool activity was less likely to appear after longer uptake times, focal background spots in bone marrow were more common. Consequently, despite a paucity of data, a negative impact of the biodistribution on clinical decision making was more often noted with increasing uptake time (P = 0.019).
DISCUSSION
In this retrospective study, we quantitatively evaluated the biodistribution and tumor uptake of the new PSMA-targeting PET tracer, 18F-rhPSMA-7. In addition, we qualitatively evaluated different uptake times and injected activities to determine those most favorable to image quality.
First, as expected, we showed that the normal biodistribution of 18F-rhPSMA-7 is similar to other that of PSMA ligands.18F-rhPSMA-7 PET exhibited high uptake in normal organs such as salivary glands and kidneys and moderate uptake in liver, spleen, and duodenum. Minimal uptake was observed in background tissue, blood pool, and lungs. The biodistribution pattern of 18F-rhPSMA-7 is in line with the known expression of PSMA/FOLH1 (8–11). Low uptake in the urinary bladder suggests clearance of 18F-rhPSMA-7 via the renal system, compared with mainly the biliary tract for 18F-PSMA1007 (6).
The kidneys and the urinary tract are important organs in the biodistribution of a novel PSMA ligand. There are known limitations with, for example, 68Ga-PSMA-11 and 18F-DCFPyL, which are excreted mainly via the urinary tract. This elimination route can hamper assessment of local tumor and locoregional lymph nodes and can even induce halo artifacts, deteriorating image quality (12,13). The uptake patterns of the kidneys and bladder suggest the urinary excretory route for 18F-rhPSMA-7. The uptake level in the kidneys was highly variable, as seen for other PSMA ligands used in PET imaging. However, one of the major strengths of 18F-rhPSMA-7 is that tracer retention in the bladder was relatively low in all time-groups and clearly lower than that for 68Ga-PSMA-11 (14).
Of note, the urinary retention observed in our analyses might be influenced by the application of furosemide at the time of tracer injection. The diuretic effect of furosemide begins within 5 min after intravenous injection and then progressively dissipates after peaking within the first 1–2 h because the plasma half-life of furosemide is 1.5–2 h (15,16). The diuretic effect is reported to continue for up to 2 h after injection (15). Moreover, the individual bioavailability of furosemide varies considerably. In the present study, tracer retention in the bladder decreased with uptake time, and we did not observe a dose–response curve according to uptake time. However, to assess the specific excretion characteristics of the tracer, a comparison to patients without administration of furosemide would be necessary.
Assessing a new 18F-labeled PSMA ligand requires determining the extent of background uptake in bone to limit false-positive findings and pitfalls (17). Bone uptake of 18F-rhPSMA-7 is relatively low, at approximately half the level of the mediastinal blood pool. However, bone uptake increased with increasing uptake time, suggesting that 18F-rhPSMA-7 accumulates in bone after specific binding. The etiology of this binding is still unknown, as PSMA expression is low in normal bone (11). Uptake in different bone pathologies (fractures, degenerative changes, fibroosseous lesions) has been reported to be related to PSMA expression in the neovasculature (9) and can be an issue for 18F-labeled PSMA ligands, as recently reported (18). The qualitative analyses also indicate that imaging after a short versus long uptake time benefits bone uptake not related to prostate cancer, which can be a potential pitfall for image interpretation.
Tumor uptake of 18F-rhPSMA-7 was in high ranges similar to those reported for other PSMA ligands, especially 68Ga-PSMA-11 (14,19). Tumor uptake was also highly variable but without significant differences across tumor locations. However, tumor localization was easily achievable with the 18F-rhPSMA-7 scan. Most tumor lesions were in the pelvis, and the average uptake of tumor lesions was sufficiently high to be distinguishable from the adjacent normal organs. In addition, as known for 68Ga-PSMA-11, bone lesions showed a significantly higher uptake of 18F-rhPSMA-7 than did soft-tissue lesions (19). No clear trend or significant differences were observed for tumor lesions across the various uptake times and administered-activity groups. Despite limitations due to the known high variation in PSMA expression in tumor lesions, these results indicate that uptake in tumor lesions is not a crucial determinant of optimal uptake time.
The qualitative image analyses revealed 18F-rhPSMA-7 to have promising properties for prostate cancer imaging and provided useful data to inform decisions on optimal uptake time. In general, overall image quality was rated as high and stable across different uptake times. Whereas longer uptake times reduced nonspecific uptake in the blood pool, background uptake or focal spots in the bone marrow were seen to increase. Despite low absolute numbers, a negative impact of the biodistribution on clinical decision making was observed at later time points. Because blood-pool activity is not particularly relevant for prostate cancer image assessment and bone is a major site of metastases, qualitative analyses suggest an early time (∼1 h after injection) as favorable for interpretation.
Regarding injected activity, our results indicate that overall image quality deteriorates with increasing administered activity. However, it is difficult to draw definitive conclusion, because our analysis found a clear correlation between patients’ body weight and administered activity. It is known that image quality in PET worsens with increasing body weight. Qualitative assessment of nonspecific blood-pool and bone uptake was not dependent on body weight.
The optimal imaging protocol for PSMA-ligand PET requires further investigation, particularly the optimal time point. Various factors, such as the kinetics of radiopharmaceuticals, the physical characteristics of radioisotopes, and the purpose of the imaging, will all likely have an impact. Imaging time point varies from early dynamic imaging to 3 h after injection for 68Ga-PSMA-11 PET (20–24). Some have advocated late imaging time points for PSMA-ligand PET; late imaging could be advantageous in detecting tumor lesions and getting a clear image mainly because of the increasing uptake of PSMA ligands over time (14,22,25–27). The preference for a late imaging time point seems to be in line with 18F-based PSMA ligands; for example, imaging time points ranged from 1 to 3 h after injection for 18F-PSMA-1007 (6,28–30). In a recent study comparing the biodistribution and tumor detection at 60 and 120 min after injection of 18F-PSMA-1007, late imaging at 120 min after injection was recommended since lesions showed significantly higher uptake and better contrast (30).
However, some have suggested that an early imaging time provides high enough diagnostic sensitivity. In a study comparing the diagnostic performance of 68Ga-PSMA-11 PET at 1 h and 3 h after injection, early imaging at 1 h provided high image quality for detection of suspected prostate cancer lesions, with late imaging at 3 h potentially providing additional information to allow better interpretation of unclear lesions (22). Late imaging could offer the benefit of a high-contrast image, but without improving overall detection rates. Our study yields results similar to previous studies. Later imaging could be helpful to acquire clear images because of less nonspecific background activity; however, the overall image quality was stable over the imaging time points investigated. The impact on clinical decision making was negative at later imaging times. Thus, we recommended early imaging time points for 18F-rhPSMA-7 to achieve the highest overall image quality.
Limitations of our study stem from its retrospective nature. Matched pairwise comparisons were unavailable, because PET imaging times and injected activities of 18F-rhPSMA-7 were heterogeneous. To reduce heterogeneity among patients, we based the groups on imaging time and injected activity, and we performed groupwise analyses. However, for the patient collective available for this analysis, fewer than 10 patients could be included in groups 4 and 12. This low number of patients could also be a potential bias for the statistical analyses. Nevertheless, because we already see a trend toward a favorable uptake time of around 1 h, we believe that the potential bias is limited. In addition, we aimed for groups with homogeneous disease by stratifying on the basis of disease state and PSA value. However, it is known that substantial differences in tumor burden can be present in different patients with the same PSA level. Lastly, our study is not a substitute for a kinetic biodistribution study, since we retrospectively analyzed data acquired in routine clinical care. Within this context, it needs to be stated that despite the low urinary retention observed in our patient cohort after the routine application of furosemide, the exact kinetics of tracer excretion have not yet been explored. An ongoing phase I study is currently investigating the biodistribution of 18F-rhPSMA7.3 (NCT03995888).
CONCLUSION
The biodistribution of 18F-rhPSMA-7 was similar to that of other established PSMA ligands with high image quality. The tumor uptake of 18F-rhPSMA-7 was stable across the administered activities and uptake times. Because low tracer retention in the urinary bladder and the presence of focal uptake in the bone marrow are important features for PSMA-ligand PET imaging, early imaging time points (50–70 min) are recommended for 18F-rhPSMA-7 to optimize image quality.
DISCLOSURE
Hans-Jürgen Wester, Alexander Wurzer, and Matthias Eiber are named as inventors on a patent application for rhPSMA. Hans-Jürgen Wester and Matthias Eiber received funding from the SFB 824 (DFG Sonderforschungsbereich 824, project B11) from the Deutsche Forschungsgemeinschaft, Bonn, Germany, and from Blue Earth Diagnostics Ltd. (licensee for rhPSMA) as part of an academic collaboration. Hans-Jürgen Wester is a founder, shareholder, and advisory board member of Scintomics GmbH, Fuerstenfeldbruck, Germany. Matthias Eiber and Wolfgang Weber are consultants for Blue Earth Diagnostics Ltd. No other potential conflict of interest relevant to this article was reported.
KEY POINTS
QUESTION: What imaging time for 18F-rhPSMA-7 PET/CT achieves the highest overall image quality?
PERTINENT FINDINGS: The biodistribution of 18F-rhPSMA-7 was similar to that of established PSMA ligands. Qualitative and quantitative analyses revealed increasing uptake in kidney, bladder, and bones over time and decreasing uptake in blood pool. Tumor uptake of 18F-rhPSMA-7 was stable.
IMPLICATIONS FOR PATIENT CARE: These results suggest an early imaging time point (50–70 min) for 18F-rhPSMA-7 PET/CT to achieve the highest overall image quality. Achieving the highest overall image quality could help patients by exact tumor localization and thus change patients’ treatment strategies properly and efficiently.
Footnotes
Published online Dec. 13, 2019.
- © 2020 by the Society of Nuclear Medicine and Molecular Imaging.
REFERENCES
- Received for publication August 8, 2019.
- Accepted for publication November 11, 2019.
Jump to section
Related Articles
Cited By...
- Validation of 18F-rhPSMA-7 and 18F-rhPSMA-7.3 PET Imaging Results with Histopathology from Salvage Surgery in Patients with Biochemical Recurrence of Prostate Cancer
- Synthesis and Preclinical Evaluation of 177Lu-Labeled Radiohybrid PSMA Ligands for Endoradiotherapy of Prostate Cancer
- Utility of 18F-rhPSMA-7.3 PET for Imaging of Primary Prostate Cancer and Preoperative Efficacy in N-Staging of Unfavorable Intermediate- to Very High-Risk Patients Validated by Histopathology
- 18F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Curative-Intent Radiation Therapy: A Bicentric Retrospective Study
- Pretherapeutic Comparative Dosimetry of 177Lu-rhPSMA-7.3 and 177Lu-PSMA I&T in Patients with Metastatic Castration-Resistant Prostate Cancer
- Comparative Preclinical Biodistribution, Dosimetry, and Endoradiotherapy in Metastatic Castration-Resistant Prostate Cancer Using 19F/177Lu-rhPSMA-7.3 and 177Lu-PSMA I&T
- Safety, Biodistribution, and Radiation Dosimetry of 18F-rhPSMA-7.3 in Healthy Adult Volunteers
- Histologically Confirmed Diagnostic Efficacy of 18F-rhPSMA-7 PET for N-Staging of Patients with Primary High-Risk Prostate Cancer