Andrea Farolfi: Hello everybody. My name is Andrea Farolfi, and I'm a nuclear medicine physician based in Bologna, Italy. And my field of interest is prostate cancer imaging with PET tracers, such as choline, fluciclovine, and PSMA ligands. I'm going to speak about how to read and report a PSMA PET, including PET terminology, PROMISE/PPP, and what is important in a PSMA PET report with a clinician view.

First of all, there are multiple molecular imaging strategies currently applied for prostate cancer. In clinical practice, there are several PET tracers, completely different mechanism of uptake. For example, there is choline, employed for phospholipids and membrane turnovers, fluciclovine for amino acids and sodium fluoride, for osteoblastic activity, and PSMA ligands , for the protein PSMA.

PSMA is the prostate specific membrane antigen, also known as folate hydrolase one, and other names, or referring to the same transmembrane protein with enzymatic activity. It's increased expression in prostate cancer cells is described, as well as in many other cancer and benign conditions. And here in the figure, we have the structure of the PSMA, with its binding sites for tracers employment path.

In the PSMA family, several PSMA ligands for PET imaging have been developed in the last years, and other will come in the next futures. However, to date, the most employed worldwide are the Gallium PSMA 11 here, and the FDA approved fluorinated, the DCFPyL here.

When approaching PET examination, the first thing to assess is the MIP. MIP is a Maximum Intensity Projection. On the left, we have one MIP, a negative scan of a prostate cancer patient. On the right side, we have a positive PSMA PET. As you can see, there are focal areas of PSMA uptake. And why look at the MIP? Because you can identify the PET tracer, you have a global overview of the physiological and pathological distribution. You improve the sense of three-dimensionality. And also you can point and view in MIP, and viewing the same findings in the axial slices.

However, the physiological biodistribution of PSMA based tracer with [inaudible 00:03:02] expression is displayed here in the figure. There is physiological PSMA expression in normal tissues, such as salivary glands, kidneys, small bowel, liver, spleen. Also, there is physiological uptake in the parasympathetic ganglia. And also, there is a physiological expression with the urinary tract. So you can see uptake areas within the ureter, the bladder, and the urethra.

However, there other PSMA-avid conditions, such as osteoblastic activity, increased vascular density, inflammatory conditions, and also, other tumors.

PET is usually associated with a CT or an MRI. Following a precise localization of the PET findings with up to date PET hybrid systems.

Now we can see how images are displayed in a nuclear medicine workstation. In the right side, we have the axle view of the PET scan. In the left side, the CT part of the examination, this is a low dose CT without contrast announcement. In the middle, the fused images PET CT. Also, we can easily display the MIP, and we can identify that this is Gallium PSMA-11. We have the salivary glands, kidneys, more bowel, the liver, the spleen, the bladder, bowels, but also several focal areas of uptake, probably due to prostate cancer.

First of all, we must start with the prostate or the prostate bed. For example, here we have an area of increased PSMA uptake in the prostate, but also in the right seminal vesicle, as you can see in the CT part of the examination.

Secondly, we look at pelvic lymph nodes. For example, here there is an area of increased abnormal PMSA uptake. And in the CT part, there is a lymph node in the right internal iliac region, and this is a metastasis. But also, other two areas of focal uptake here, and here. And thanks to the CT part of the examination, we can follow them, and we can see that this is physiological urine within the right and the left ureter.

Moving up within the pelvis, again, radioactive urine in the left ureter. Thanks to the CT part, we can follow the ureter. And so this is a patient with PSMA uptake, pathological uptake within the prostate, the right seminal vesicle, the one lymph node in the pelvis. And going up.

Also, we have one lymph node here and in the mediastinum. Another two areas of uptake here in the left film. Going to assert the lungs. We have a few small nodules without any in the right lung, without focal uptake. But also, one small nodule here with faint uptake of PSMA here, as you can see, there is little mismatch, due to patient breathing.

And at the end, we assess the bone. And we can see here, one arrow uptake, and also another one here, and the third one here. So this is a patient with also distant metastasis, lymph nodes, lung, probably, and bone metastasis.

Going back to the presentation. One important characteristic of PET images is the possibility to assess the intensity of uptake. And PROMISE proposed the PSMA expression score, based on visual assessment, and categories defined the relation to mean uptake or reference organs. As you can see in the picture, the reference organs are the blood-pool, the liver, and parotid glands. And also, PSMA intensity can be measured in any area with the Standardized Uptake Value, the SUV. That is the ratio of activity per unit volume of region of interest, to the activity per unit, whole body volume.

And also, in order to standardize the evaluation PROMISE categories, allow to classify the local tumor, and in case of radical prostatectomy, the prostate bed, in case of relapse. But also, regional nodes and distant metastases, ranging from pelvic lymph nodes to distant lymph nodes, to visual mets. And also, a pattern of bone involvement, ranging from unifocal to oligometastatic and disseminated bone metastasis.

Also, the author suggests to adopt a standard template for pelvic lymph node regions, in order to align the nuclear medicine physician with the clinicians when reporting lymph node regions within the pelvis.

There is also the reader confidence assessed by PSMA-RADS. PSMA-RADS is a classification of PSMA PET findings into categories that reflect the likelihood of the present of prostate cancer. Like the other radiological RADS criteria, the goal of PSMA-RADS is to score the level of confidence of the reader, in the presence of prostate cancer, and the potential need for any additional workup.

The scores for PSMA-RADS range from one to five, with higher number indicating a greater probability of prostate cancer. And in addition, the order of the classification also recommend the full clinical history before any PSMA PET scan.

Regarding disease progression, a panel of international expert proposed the PSMA PET progression criteria, also known as PPP, in order to define prostate cancer progression by PSMA PET. They build this criteria starting from the PCWG2 and three criteria. And also, the PPP can be applied for any focal and systemic therapy.

There are three main criteria. The first one is the appearance of two or more new PSMA positive distant lesions, because PSMA PET is significantly more sensitive, but also more specific than bone scan. The single presentation of two new lesions is sufficient for progression.

Another criterion for progression is the appearance of one new PSMA-positive lesion, plus consistent clinical or laboratory data, a recommended confirmation by biopsy of correlative imaging within three months of the date of PET.

And the last criteria is no new lesions, but size increase by 30% or higher, in size or uptake. Plus consistent clinical or laboratory data, and confirmation by biopsy or correlative imaging within three months the date of PET.

And what is important to report after a PSMA PET for the clinician? The European Association of Nuclear Medicine standardized reporting guideline proposed the template, starting with an anatomical location of the findings, and then moving to the molecular imaging TNM based on PROMISE criteria. The size of the findings taken in the CT on the MRI part of the examination. The number of the lesion in this specific anatomical location. And then, the assessment of the PSMA expression, both quantitative, for example, with the SUVmax, and the qualitative with the visual assessment. At the end, the reader confidence expressed through a five point scale.

To conclude, PSMA is expressed in a variety of normal tissues, tissue neovasculature, and some tumor types, both benign and malignant. For this region, patient history is necessary for accurate interpretation. However, PSMA PET is easy to interpret, compared to other radiological imaging modalities. And PSMA level of expression are determined in relation with reference organs, parotid gland, liver, and blood-pool. And there is a need of standardized template for disease location, in order to align the nuclear medical physician with the clinician, mostly for pelvic lymph nodes regions.

And thank you.