Anna Yordanova

// Hojjat Ahmadzadehfar 1 , Elisabeth Eppard 1 , Stefan Kürpig 1 , Rolf Fimmers 2 , Anna Yordanova 1 , Carl Diedrich Schlenkhoff 1 , Florian Gärtner 1 , Sebastian Rogenhofer 3 , Markus Essler 1 1 Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany 2 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany 3 Department of Urology, University Hospital Bonn, Bonn, Germany Correspondence to: Hojjat Ahmadzadehfar, e-mail: Hojjat.ahmadzadehfar@ukb.uni-bonn.de , nuclearmedicine@gmail.com Keywords: PSMA, 177 Lu, prostate cancer, radioligand therapy, PSA Received: October 26, 2015     Accepted: January 27, 2016     Published: February 08, 2016 ABSTRACT Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with 177 Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64–82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17–2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients.

The importance of personalized medicine has been growing, mainly due to a more urgent need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for specific molecular targeting, both for diagnostics and therapy. The visualization of potential targets can help predict if a patient will benefit from a particular treatment. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents has been continually increasing. In this article, important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with a well-known radioiodine therapy in patients with thyroid cancer and then progresses through various approaches for the treatment of advanced cancer with targeted therapies. The aim of this review was to provide a summary of background knowledge and current applications, and to identify the advantages of targeted therapies and imaging in nuclear medicine practices.

UNLABELLED: Radiolabeled prostate-specific membrane antigen (PSMA) ligands represent a true theranostic concept for diagnosis and therapy in patients with relapsed or metastatic prostate cancer. The aim of this study was to evaluate the response to and tolerability of a single dose of (177)Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: The data of 82 consecutive patients (median age, 73 y; range, 43-87 y) with mCRPC who received a single dose of (177)Lu-PSMA-617 (mean, 5.9 ± 0.5 GBq) were retrospectively analyzed. Data were collected at baseline and 8 wk after therapy. (68)Ga-PSMA-11 PET/CT was performed on all patients to verify sufficient PSMA expression. Bone, lymph node, liver, and lung metastases were present in 99%, 65%, 17%, and 11% of the patients, respectively. Tolerability and response were evaluated using hematologic parameters, renal scintigraphy, clinical data, and the prostate-specific antigen (PSA) level at baseline and 8 wk after therapy application. RESULTS: Six patients died, and 2 patients dropped out because they were not willing to continue therapy and follow-up. The complete dataset of 74 patients was available for analysis. Forty-seven patients (64%) showed a PSA decline, including 23 (31%) with a decline by more than 50%. Thirty-five patients (47%) had stable disease: the change in their PSA level ranged from less than a 50% decline to less than a 25% rise. Seventeen patients (23%) had progressive disease: their PSA level rose by more than 25%. There were no significant changes in hemoglobin, white blood cells, creatinine, or tubular extraction rates indicative of toxicity. There was a significant but mild decrease in platelets, but the median value was still within the reference range. CONCLUSION: This retrospective multicenter analysis suggests that radioligand therapy with (177)Lu-PSMA-617 is safe and well tolerated and has a considerable effect on PSA level. Therefore, it offers an additional therapeutic option for patients with mCRPC. These data may justify further prospective randomized studies to evaluate and prove the clinical benefit in terms of survival and quality of life.