PSMA: A Windfall for PET/CT Imaging

⁶⁸Ga-labelled PSMA-11 was developed by Professor Michael Eisenhut and Matthias Eder, MD at the German Cancer Research Center (DKFZ) in Heidelberg, Germany. Professor Uwe Haberkorn, who directs the nuclear medicine clinic in Heidelberg, first deployed the novel tracer in compassionate use four years ago. In the meantime, several hundred such instances worldwide have shown that ⁶⁸Ga-labelled PSMA-11 detects recurrent prostate cancer at a high level of sensitivity in PET/CT scans.^{2, 3, 4} Detection of lymph node metastases is below the threshold of other usual imaging methods. However, there is still a lack of prospective clinical data on ⁶⁸Ga PSMA-11 imaging.

These data are now to be captured in an exclusively academically funded multicenter clinical trial under the umbrella of the German Consortium for Translational Cancer Research (DKTK), or in short, the German Cancer Consortium. This makes the clinical trial a great milestone in translational medicine. Responsible for planning and organization are Professor Frederik Giesel at Heidelberg University Hospital and Professor Klaus Kopka at the DKFZ. Giesel is vice chair of the Nuclear Medicine department and the clinical trial director. Kopka is a chemist who heads the Division of Radiopharmaceutical Chemistry at the DKFZ. He is responsible radiopharmaceutical coordinator of the prospective study. The two are an excellent tandem crew for this unique bridging of basic research and clinical practice.

Why is this prospective phase I and II clinical trial so important? “The PET/CT imaging data gathered for prostate carcinoma with ⁶⁸Ga-labelled PSMA-11 so far are retrospective data, where the PSMA-PET/CT imaging was compared with the choline-PET/CT imaging that is usually used for the diagnosis of prostate carcinoma,” explains Giesel. “While these results are groundbreaking to the extent they have shown that ⁶⁸Ga-labelled PSMA-11 is more sensitive than the choline tracer for diagnosing recurrent prostate cancer,^{2, 3, 4} only prospective trials count when it comes to inclusion in clinical guidelines and having the costs covered. So retrospective studies aren’t really much use,” continues Giesel.

They are not accepted as a basis for guidelines because they are not homogenized (harmonized) and are only based on individual cases of compassionate use. But the potential of the new diagnostic tracer is already underscored by the fact that due to the extraordinarily good results for PSMAPET/ CT imaging in retrospective studies, the method has already been included, even without prospective data, in the proposed amendments for the next revision of the German clinical guidelines. Which centers are behind the prospective clinical trial? “Seven of the eight DKTK centers will be involved, along with four other sites,” says Kopka, “including one in Austria, and one in Switzerland.” He explains the trial will be funded primarily by the German Cancer Consortium, and that it is already seen as a type of role model for translational clinical studies in nuclear medicine. “Our trial is a flagship project. In Germany, we’re right at the forefront in terms of translation in cancer research.”

What precisely are they planning? “The clinical trial will include 150 high-risk patients with prostate cancer before radical prostatectomy,” says Giesel. “It will begin in quarter 2 of 2017. Patients with a high PSA value and a positive biopsy, and have not yet received therapy, are included. ⁶⁸Ga-labelled PSMA-11 PET/CT imaging will then be done prior to prostatectomy to check the extent to which the tracer correctly reflects the staging and the spread of the lesions determined in surgery,” Giesel continues. To assure the comparability of data, the biopsy and the pathological examination of the tissue samples will be standardized. “The ⁶⁸Ga-labelled PSMA-11 PET/CT scan will be quantified by cross-calibrating with a phantom,” explains Kopka.

But PSMA is not just an excellent candidate for imaging; together with a therapeutic radionuclide it can also be used for therapy. Did they consider the possibility of combining diagnosis and therapy from the outset? “It developed as things progressed,” says Kopka. “Imaging allows you to get to the tumor and decide whether endoradiotherapy makes sense. Given the biodistribution of ⁶⁸Ga-labelled PSMA-11, it was immediately clear that we should develop a therapeutic option. We then did precisely that with 177Lu-labelled PSMA-617.” This therapeutic variant has already been licensed out to ABX advanced biochemical compounds.