Impact of Next Generation Imaging: What Is the Optimal (Current) Tracer for PET-Based Imaging for Staging Presentation - Ken Herrmann

August 2, 2022

Ken Herrmann presents an update on the current data regarding optimal PSMA PET tracers.


Ken Herrmann, MD, MBA, Professor and Chair of the Department of Nuclear Medicine, Universitatsklinikum Essen, Essen, Germany

The Mechanism of PSMA PET for Prostate Cancer - Stefano Fanti and Ken Herrmann

APCCC 2021: PSMA-Based Imaging: Navigating the Pitfalls of the Different Tracers

Read the Full Video Transcript

( The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on high-risk and locally advanced prostate cancer and a presentation by Dr. Ken Herrmann discussing the impact of next generation imaging and the optimal tracer for PET-based imaging for staging. To set the stage, Dr. Herrmann notes that we are nearly a decade since the first report of human application of PSMA PET/CT, with several available 68Ga-labeled PSMA ligands (68Ga-PSMA-11, 68Ga-PSMA-I&T) and 18F-labeled PSMA ligands (18F-DCFBC, 18F-DCFPyL, 18F-PSMA-1007, 18F-rhPSMA7):




Dr. Herrmann notes that the majority of his discussion focuses on 68Ga-PSMA-11, 18F-DCFPyL and 18F-PSMA-1007, with the overall current PSMA PET/CT landscape as follows:




Dr. Herrmann emphasied that there is excellent evidence for both 68Ga-PSMA and 18F-PSMA PET/CT. Hope et al.1 published in 2021 a phase 3 imaging trial assessing the accuracy of 68Ga-PSMA-11 PET imaging for the detection of pelvic nodal metastases compared with histopathology at time of radical prostatectomy and pelvic lymph node dissection. In this trial, there were 764 men that underwent a 68Ga-PSMA-11 PET imaging scan for primary staging, and 277 of 764 (36%) subsequently underwent prostatectomy with lymph node dissection. Based on pathology reports, 75 of 277 patients (27%) had pelvic nodal metastasis. Results of 68Ga-PSMA-11 PET/CT were positive in 40 of 277 (14%), 2 of 277 (1%), and 7 of 277 (3%) of patients for pelvic nodal, extrapelvic nodal, and bone metastatic disease, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for pelvic nodal metastases were 0.40 (95% CI, 0.34-0.46), 0.95 (95% CI, 0.92-0.97), 0.75 (95% CI, 0.70-0.80), and 0.81 (95% CI, 0.76-0.85), respectively. Fendler and colleagues2 also assessed 68Ga-PSMA-11 PET/CT accuracy in a prospective multicenter trial among 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%). On a per-patient basis, positive predictive value was 0.84 (95% CI, 0.75-0.90) by histopathologic validation and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217), with 68Ga-PSMA-11 PET/CT localizing recurrent prostate cancer in 475 of 635 (75%) patients. The detection rates stratified by PSA are as follows:




With regards to 18F-DCFPyL PSMA PET/CT, there is evidence from both the CONDOR3 and OSPREY4 clinical trials. In CONDOR, patients were recruited that had biochemically recurrent disease and rising PSA after definitive therapy and negative or equivocal standard of care imaging (e.g., CT/MRI, bone scintigraphy, or F-18 fluciclovine). Patients with positive 18F-DCFPyL-PET/CT scans based on local interpretation were scheduled for follow up within 60 days to verify suspected lesion(s) using a composite standard of truth. As their primary outcome of interest, the authors assessed the correct localization rate (CLR), defined as percentage of patients with a 1:1 correspondence between at least one lesion identified by DCFPyL-PET/CT and the composite standard of truth: pathology, correlative imaging, or PSA response, in descending order of priority. Among 208 men, the median PSA was 0.8 [0.2 - 98.4] ng/mL, and the primary outcome of correct localization rate for DCFPyL-PET/CT was 84.8-87.0% of cases among the three readers (lower bound of 95% CI: 77.8%-80.4%), against the composite standard of truth. The OSPREY trial was a prospective trial designed to determine the diagnostic performance of 18F-DCFPyL-PET/CT for detecting sites of metastatic prostate cancer. Cohort A enrolled men with high-risk prostate cancer undergoing radical prostatectomy with pelvic lymphadenectomy. In this cohort of 252 patients, 18F-DCFPyL-PET/CT had median specificity of 97.9% (95% CI: 94.5%-99.4%) and median sensitivity of 40.3% (28.1%-52.5%, not meeting prespecified end point) among 3 readers for pelvic nodal involvement. Additionally, the median positive predictive value and negative predictive value were 86.7% (69.7%-95.3%) and 83.2% (78.2%-88.1%), respectively:





Additional evidence for PSMA PET/CT is provided by the proPSMA study.5 In this trial, 302 men were randomly assigned to conventional imaging (n=152) and PSMA PET-CT (n=150). PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0.0001). Additionally, this trial found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT. 

Dr. Herrmann notes that there are pros and cons to 68Ga-PSMA-11, 18F-DCFPyL and 18F-PSMA-1007. For 68Ga-PSMA-11, the pros are (i) that proPSMA was done with 68Ga-PSMA-11, (ii) the overall majority of data is from this tracer, and (iii) it is widely available (FDA approved, 2 EMA submissions pending). The two main cons of 68Ga-PSMA-11 are that there are logistic challenges and that it is excreted via the kidneys and urinary tract. For 18F-DCFPyL, the pros are (i) it is FDA approved, (ii) the OSPRETY trial provides evidence in primary staging, and (iii) there are logistical advantages. The two main cons of 18F-DCFPyL are that it is excreted via the kidneys and urinary tract and there is less data than for 68Ga-PSMA-11. For 18F-PSMA-1007, the pros are that it is predominantly excreted via the GI tract and there is market approval in France, whereas the cons are that it has the least data among the three front runners and unspecific bone uptake is a major challenge (~50%).


Dr. Herrmann concluded his presentation by discussing the impact of next-generation imaging and the optimal tracer for PET-based imaging for staging with the following take home messages:

  • PSMA PET/CT is implemented into the clinical guidelines (NCCN, EAU)
  • Differences between PSMA PET/CT tracers exist
  • Most data so far are available for PSMA-11 and PyL, with both mainly being excreted via the kidneys
  • PSMA-1007 is predominantly excreted via the GI tract, but there are challenges of unspecific bone uptake


Presented By: Ken Herrmann, MD, MBA, University of Duisburg-Essen, University Hospital Essen, Essen, Germany

Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Annual Hybrid Meeting, Lugano, Switzerland, Thurs, Apr 28 – Sat, Apr 30, 2022.


  1. Hope TA, Eiber M, Armstrong WR, et al. Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial. JAMA Oncol. 2021 Nov 1;7(11):1635-1642.
  2. Fendler WP, Calais J, Eiber M, et al. Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol 2019 Jun 1;5(6):856-863.
  3. Morris MJ, Rowe SP, Gorin MA, et al. Diagnostic Performance of 18F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study. Clin Cancer Res. 2021 Feb 23 [Epub ahead of print].
  4. Pienta KJ, Gorin MA, Rowe SP, et al. A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). J Urol. 2021 Jul;206(1):52-61.
  5. Hofman MS, Lawrentschuk N, Francis, RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomized, multicentre study. Lancet 2020 Apr 11;395(10231):1208-1216.


Speaker 1: So thank you. So let's start immediately with the first session on high-risk and locally advanced prostate cancer. I'm very privileged to have Dr. Vapiwala with me here. And I'm also very, very happy that this table really represents a strong distribution of stakeholders in prostate cancer with four urologists around the table. So the debate will be very intense. So we start with a nuclear physicist. Dr. Herrmann from Essen will actually give you an update on the optimal tracer for PET basing imaging. And then we're going to move directly to some debate.

Dr. Herrmann: So thank you very much for the kind introduction. I hope it's not part of my 10 minutes. So these are my disclosures. Apart from the academic ones, none of them are related to this talk. Indeed, I'm bringing you a slide showing you an overview of the most commonly used PSMA PET tracers. The differences of the tracers are to one side, the radionucleotides. For example, Gallium-68, mainly generator produced, short half-life of 68 minutes. The Fluo-18 is labeled on the right side. Another differentiation of the tracers is the way they are primarily excreted. The four tracers on the left side mainly excrete via the kidneys. That's why a lot of physiological uptake in the kidneys but also in the urinary/bladder, which again might confound the diagnosis in the prostate or in case of [inaudible 00:01:25] where the two tracers on the right side predominantly excrete via the GI tract, therefore less uptake in the urinary/bladder.

Overall, you have seen that the biodistribution looks very similar to them on all of them. This isn't a comprehensive, even not exhaustive overview of all the PSMA tracers currently being developed. We saw Christina Mueller is having even a couple of more currently working on. I want to highlight quickly those three tracers marked in red. I start with Gallium-PSMA-11. This one is FDA-approved actually in three different forms. A kit from Telix, a kit from Novartis, as well as the academic UCLA, UCSF approval. And we hope obviously that this will also happen soon in Europe. The second compound is DCFPyL. It's approved in the US by Progenics. It's a Fluo-18 compound widely available. And the third one, it's the 1007, which is currently having at least the market authorization in France, and here we also expect more and more countries to make it available in Europe over the year.

Now what is the data which really led to the FDA approvals? On the left side, the two key papers for the academic UCLA, UCSF approval. First in primary staging, more than 700 patients were included, 277 underwent radical prostate lymph node dissection. And here the sensitivity was 40% and the specificity was 95%. On the lower bottom, the second paper, this [inaudible 00:02:50] biochemical recurrence. He PSMA PET showed high 30% detection rate for PSA smaller than 0.5, increasing to well above 80% if the PSA is greater than one. Interestingly, the primary endpoint for the study and also for the approval was indeed the positive predictive value being 84% in case of histopathology confirmation and if imaging was used, it even increased to 92%.

On the right side, I'm highlighting the two publications which led to the approval of PyL. On the top, the CONDOR study, [inaudible 00:03:23] here primary staging, and you can see sensitivity for the detection of pelvic lymph nodes was 40%, specificity, 98% and the positive predictive value, 87%. And then the CONDOR trial with Michael Morris, also being in the audience as the first author. Again, we see similar detection rates as for PSMA-11, increasing significantly with higher PSA values. And here the primary endpoint was indeed the correct localization rate being 87%.

And then obviously a very important paper I need to show of the proPSMA study from Australia. Very important because here patients were randomized into either PSMA PET or morphological imaging and then afterwards had the other imaging modality. This included high-risk patients, as well as unfavorable, intermediate-risk patients. We can see that PSMA PET/CT was indeed significantly more accurate than morphological imaging independent if it was any metastatic disease, pelvic nodal or distant metastasis. And if you look to the right, we can see that this is mainly driven by a higher sensitivity of PSMA PET/CT compared to morphologically imaging.

Now, coming back to the initial idea of my talk is to tell you a little bit what are the three main candidates and which are the best ones. The first candidate PSMA-11, big advantage is that proPSMA was done with this trial, [inaudible 00:04:41] was done with this tracer. The majority of data we have in this tracer, it's widely available. Three of them are FDA approved and two submissions are currently pending. A clear downside is the logistical challenge. It's a generator product mainly. It's, well, lower yield and it's excreted via the kidneys and the urinary tract, which again gives us the problem of potentially high physiological uptake in the urinary/bladder, which impacts potentially the diagnosis of the tumor and the prostate itself in case of low recurrence.

PyL, Fluo-18 labeled, very similar biodistribution, also FDA approved. The OSPREY data I showed you is in this trace. Logistically better than Gallium-PSMA-11, because it's [inaudible 00:05:20] produced, high yield and vitally available. Downside is less data than for PSMA-11 and again also like PSMA-11 excreted via the kidneys and the urinary tract.

Now the third candidate PSMA 1007, this is predominantly excreted via the GI tract, which again as you can see here very nicely makes it probably easier to identify disease in the prostate also, in case of local recurrence. We do have a market approval in France, but compared to the other tracers, we have the least data of this front-runner and then there's the topic of unspecific bone uptake, which I'm going to dedicate two quick slides. This is a retrospective [inaudible 00:05:54] from Switzerland, 348 patients. In more than 50% of the patients, they reported unspecific bone uptake, a higher likelihood of unspecific bone uptake in digital PET/CT as you can see in blue, as well as in an early imaging situation. Obviously, the clinical situation is exactly that digital scanners and we try to image early.

The locations where we do find this unspecific bone uptake is mainly the ribs, the pelvis and the spine and to less degree, in the extremities, sternum, and very rare in the skull. To underline this, this is one of our own practice. This is one of our first patients, primary staging. In addition to this, yeah, disease, we can see very nicely in the prostate but also in the lymph nodes. We do see this uptake in the scapula. This patient from the whole clinical sedation didn't really fit the pattern. So we performed another PSMA-11 scan. We performed a bone scan. And you can very nicely see here that indeed we could not confirm the uptake in the other two modalities and also then later follow-up, clinical follow-up, confirmed that this uptake in 1007 is indeed unspecific bone uptake, not metastasis.

So in summary, PSMA PET is implemented into the clinical guidelines actually more widely now in the NCCN compared to the European ones. There are different uptake patterns for the various PSMA tracers. The majority of data is available for PSMA-11 and PyL. Both of them mainly excrete via the kidney, yeah, with the problem of potentially physiological uptake in the urinary/bladder. 1007, mainly excreted via the GI tract, but the big challenge of the unspecific bone uptake. Thank you very much.

Dr. Vapiwala: Just a note for the audience. Feel free to submit your questions through the format and we'll address them all at the end during the Q&A session-