Lutetium-177-PSMA therapy

Therapy for patients with metastasized prostate cancer with Lutetium-177-PSMA has been established in our hospital already in 2014. Lu-177-PSMA is a new therapy option for patients with metastasized prostate cancer when antihormonal treatments and chemotherapy are no longer effective. In contrast to other radionuclide therapy forms for prostate cancer, such as radium-223-dichloride (Xofigo®) or samarium-153, which only target bone metastases of prostate cancer, Lu-177-PSMA can treat all tumour localizations such as e.g. bone metastases, lymph node metastases and other organ metastases.

How does therapy with Lu-177-PSMA work?

 

PSMA is an abbreviation for Prostate Specific Membrane Antigen. PSMA is a protein that can regularly be found on the surface of prostate cancer cells. For use in nuclear medicine diagnostics and therapy, radioactively labelled substances that specifically bind to PSMA (key-and-lock principle) have been developed. Gallium-68-labelled PSMA is usually employed for diagnostic purposes in Ga-68-PET/CT imaging, whereas Lutetium-177-labelled PSMA is the substance of choice for therapeutic applications. Due to the specific binding of these compounds to PSMA on the surface of the tumour cells, the radioactive nuclide Lu-177 accumulates in the malignant tumour and the emitted beta-radiation kills the tumour cells with high efficacy, just like an internal radiotherapy. Due to the very short range of the beta-radiation of Lu-177 in human tissue (only about 1 mm), very high radiation doses can be delivered directly to the tumour in a highly conformal manner, meaning that the surrounding healthy tissue is mostly spared from the effects of the radiation.

From well over 1000 cycles of therapy performed in our institution, we know that up to 70% of patients (who do not have any other therapy options available anymore) benefit from Lu-177-PSMA therapy, which results in shrinkage of tumour masses, decrease of the tumour marker PSA and mitigation of pain and other symptoms.

Indications for Lu-177-PSMA therapy

Patients who are initially diagnosed with prostate cancer often undergo surgical treatment or radiotherapy. Despite optimal initial treatment relapses can occur, which in many cases can be controlled with e.g. antihormonal treatment for an extended time period. However, the tumour cells can develop resistance against these antihormonal treatments and patients might have to undergo chemotherapy, to which the tumour cells also can develop resistance during the course of treatment.

This scenario is a typical indication for Lu-177-PSMA therapy. It is a new and promising therapy option for patients with prostate cancer when no other therapy options are available. Lu-177-PSMA therapy is not a first-line therapy. This is also recommended by the S3-guidelines for prostate cancer (recommendation 6.45).

Lu-177-PSMA therapy is only possible when the tumour and metastases are PSMA-positive.
This is assessed by a Ga-68-PSMA PET/CT examination before Lu-177-PSMA therapy (figure 1). Of course, the Ga-68-PSMA PET/CT examination can also be performed in our institution.

Figure 1: Ga-68-PSMA PET/CT showing several PSMA-positive metastases of prostate cancer.

How is Lu-177-PSMA therapy performed?

Lu-177-PSMA therapy is performed on our inpatient radionuclide therapy ward (“Station Winkler”) in the University Hospital Bonn. After an initial physical examination, laboratory blood values are assessed. Furthermore, the kidney function is assessed by a scintigraphic examination (MAG3 renal scan) to exclude a urinary obstruction. About 20 – 30 minutes before application of Lu-177-PSMA, cooling of the salivary glands with ice packs is started (see figure 2), which reduces blood flow to the salivary glands to minimize unwanted uptake of Lu-177 in the salivary glands. Cooling of the salivary glands is continued for about 4 hours after the application of Lu-177-PSMA.

 Figure 2: Cooling of the salivary glands.

Lu-177-PSMA is injected intravenously, followed by an infusion of about 500 – 1000 mL of fluid. Due to radiation safety regulations, patients have to stay on the inpatient therapy ward for 48 hours after injection of Lu-177-PSMA. After the therapy, distribution of the therapeutic agent is assessed by a whole body scintigraphy to document tumour uptake (see figure 3). All personal belongings that you may have brought with you for your stay on the inpatient ward (e.g. books, laptop, smartphone, tablet, clothing, etc.) can be taken home directly after therapy. All patient rooms are equipped with personal flat-screen TVs. Wifi is available.

Figure 3: Whole body scintigraphy 24 hours after application of Lu-177-PSMA therapy, showing excellent uptake of the therapeutic agent in the metastases.

Number of therapy cycles

Lu-177-PSMA therapy consists of several cycles, initially often between 3 – 5 cycles, depending on tumour burden and individual response to therapy. The therapy cycles take place every 6 – 8 weeks.

Can Lu-177-PSMA therapy be repeated?

Lu-177-PSMA therapy can be repeated if there is a disease relapse after initial response to Lu-177-PSMA therapy.

What are the side effects of Lu-177-PSMA therapy?

Usually, Lu-177-PSMA therapy is tolerated very well and it does not lead to serious acute side effects. However, blood values (kidney function and blood cell counts) have to be checked before therapy and periodically after therapy. According to several retrospective studies, significant impairment of kidney function occurs only very rarely, even after several cycles of Lu-177-PSMA therapy. Significant changes of blood cell counts may occur in up to 10% of patients after several cycles of Lu-177-PSMA therapy.

How can I apply for Lu-177-PSMA therapy?

You or your treating physician can contact our therapy secretary’s office (contact data see below) to organize Lu-177-PSMA therapy. After an initial check of your disease history and the current disease state (e.g. current imaging studies), a Ga-68-PSMA PET/CT examination can be organized in our institution (not necessary if a PSMA PET/CT examination has already been performed recently). An interdisciplinary tumour board focused on urological tumours in our institution will then check if Lu-177-PSMA therapy is the recommended therapy for you (this is not necessary if a recommendation of an interdisciplinary tumour board of another institution is already available).

Therapy secretary office / enquiries

Mrs. Oregan Vautey

Tel: +49 (0)228 287 16171

Email: therapie.nuklearmedizin@ukbonn.de

 

Online appointment form

 

Therapy Ward

Tel: +49 (0)228 287 16855

Fax: +49 (0)228 287 19107

 

Scientific publications about Lu-177-PSMA therapy from our institution

 

Outcome and safety of rechallenge [¹⁷⁷Lu]Lu-PSMA-617 in patients with metastatic prostate cancer.

 

Yordanova A, Linden P, Hauser S, Meisenheimer M, Kürpig S, Feldmann G, Gaertner FC, Essler M, Ahmadzadehfar H.

Eur J Nucl Med Mol Imaging. 2018 Nov 24. doi: 10.1007/s00259-018-4222-x.

 

Role of textural heterogeneity parameters in patient selection for ¹⁷⁷Lu-PSMA therapy via response prediction.

 

Khurshid Z, Ahmadzadehfar H, Gaertner FC, Papp L, Zsóter N, Essler M, Bundschuh RA.

Oncotarget. 2018 Sep 7;9(70):33312-33321. doi: 10.18632/oncotarget.26051.

 

[¹⁷⁷Lu]-PSMA-617 radionuclide therapy in patients with metastatic castration-resistant prostate cancer.

 

Rahbar K, Ahmadzadehfar H, Seifert R, Boegemann M.

Lancet Oncol. 2018 Aug;19(8):e371. doi: 10.1016/S1470-2045(18)30410-8.

 

PSMA Theranostics: Current Status and Future Directions.

 

Rahbar K, Afshar-Oromieh A, Jadvar H, Ahmadzadehfar H.

Mol Imaging. 2018 Jan-Dec;17:1536012118776068. doi: 10.1177/1536012118776068. Review.

 

 

 

Radioligand therapy of metastatic castration-resistant prostate cancer: current approaches.

 

Awang ZH, Essler M, Ahmadzadehfar H.

Radiat Oncol. 2018 May 23;13(1):98. doi: 10.1186/s13014-018-1037-7. Review.

 

BRCA2 Mutation as a Possible Cause of Poor Response to 177Lu-PSMA Therapy.

Ahmadzadehfar H, Gaertner F, Lossin PS, Schwarz B, Essler M.

 Clin Nucl Med. 2018 Aug;43(8):609-610. doi: 10.1097/RLU.0000000000002141.

  

Prediction of Normal Organ Absorbed Doses for [¹⁷⁷Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.

Khawar A, Eppard E, Sinnes JP, Roesch F, Ahmadzadehfar H, Kürpig S, Meisenheimer M, Gaertner FC, Essler M, Bundschuh RA.

 Clin Nucl Med. 2018 Jul;43(7):486-491. doi: 10.1097/RLU.0000000000002102.

 

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein].

 Ahmadzadehfar H, Albers P, Bockisch A, Boegemann M, Böhme C, Burchert W, Dietlein M, Drzezga A, Fabry U, Feldmann G, Heidenreich A, Heinzel A, Herrmann K, Heyll A, Höhling C, Kreuzer C, Laufer D, Mengel R, Mottaghy FM, Müller HW, Müller SC, Ost E, Rahbar K, Reifenhäuser W, Schäfers M, Schlenkhoff C, Schmidt M, Schmidt-Wolf I, Wildenhain C, Zimmer B, Essler M.

Urologe A. 2018 Jun;57(6):709-713. doi: 10.1007/s00120-018-0642-2. Review. German

 

Predictive Factors of Response and Overall Survival in Patients with Castration-Resistant Metastatic Prostate Cancer Undergoing ¹⁷⁷Lu-PSMA Therapy.

Ahmadzadehfar H, Essler M.

J Nucl Med. 2018 Jul;59(7):1033-1034. doi: 10.2967/jnumed.118.209270.

  

[44Sc]Sc-PSMA-617 Biodistribution and Dosimetry in Patients With Metastatic Castration-Resistant Prostate Carcinoma.

Khawar A, Eppard E, Sinnes JP, Roesch F, Ahmadzadehfar H, Kürpig S, Meisenheimer M, Gaertner FC, Essler M, Bundschuh RA.

Clin Nucl Med. 2018 May;43(5):323-330. doi: 10.1097/RLU.0000000000002003.

 

Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy.

Tolkach Y, Gevensleben H, Bundschuh R, Koyun A, Huber D, Kehrer C, Hecking T, Keyver-Paik MD, Kaiser C, Ahmadzadehfar H, Essler M, Kuhn W, Kristiansen G.

Breast Cancer Res Treat. 2018 Jun;169(3):447-455. doi: 10.1007/s10549-018-4717-y

 

Predictors of overall survival in metastatic castration-resistant prostate cancer patients receiving [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy.

Ahmadzadehfar H, Schlolaut S, Fimmers R, Yordanova A, Hirzebruch S, Schlenkhoff C, Gaertner FC, Awang ZH, Hauser S, Essler M.

Oncotarget. 2017 Oct 7;8(61):103108-103116. doi: 10.18632/oncotarget.21600.

 

^{177Lu-PSMA-617 radioligand therapy in mCRPC: ready for phase III trial?}

Rahbar K, Ahmadzadehfar H, Boegemann M.

Eur J Nucl Med Mol Imaging. 2018 Mar;45(3):513-514. doi: 10.1007/s00259-017-3892-0

 

Delayed response after repeated ¹⁷⁷Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer.

Rahbar K, Bögeman M, Yordanova A, Eveslage M, Schäfers M, Essler M, Ahmadzadehfar H.

Eur J Nucl Med Mol Imaging. 2018 Feb;45(2):243-246. doi: 10.1007/s00259-017-3877-z.

 

 

PSMA targeted radioligandtherapy in metastatic castration resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival.

Rahbar K, Boegemann M, Yordanova A, Eveslage M, Schäfers M, Essler M, Ahmadzadehfar H.

Eur J Nucl Med Mol Imaging. 2018 Jan;45(1):12-19. doi: 10.1007/s00259-017-3848-4

 

Radioligand therapy of metastatic prostate cancer using ¹⁷⁷Lu-PSMA-617 after radiation exposure to ²²³Ra-dichloride.

Ahmadzadehfar H, Zimbelmann S, Yordanova A, Fimmers R, Kürpig S, Eppard E, Gaertner FC, Wei X, Hauser S, Essler M.

Oncotarget. 2017 Feb 25;8(33):55567-55574. doi: 10.18632/oncotarget.15698

 

Combination of ¹⁷⁷Lu-PSMA-617 and External Radiotherapy for the Treatment of Cerebral Metastases in Patients With Castration-Resistant Metastatic Prostate Cancer.

Wei X, Schlenkhoff C, Schwarz B, Essler M, Ahmadzadehfar H.

Clin Nucl Med. 2017 Sep;42(9):704-706. doi: 10.1097/RLU.0000000000001763.

 

Possible Treatment Approach to an Extravasation of ¹⁷⁷Lu-PSMA-617.

Schlenkhoff CD, Essler M, Ahmadzadehfar H.

Clin Nucl Med. 2017 Aug;42(8):639-640. doi: 10.1097/RLU.0000000000001715.

 

 

Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [¹⁷⁷Lu]Lu-PSMA-617.

Ahmadzadehfar H, Wegen S, Yordanova A, Fimmers R, Kürpig S, Eppard E, Wei X, Schlenkhoff C, Hauser S, Essler M.

Eur J Nucl Med Mol Imaging. 2017 Aug;44(9):1448-1454. doi: 10.1007/s00259-017-3716-2

 

The impact of repeated cycles of radioligand therapy using [¹⁷⁷Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer.

Yordanova A, Becker A, Eppard E, Kürpig S, Fisang C, Feldmann G, Essler M, Ahmadzadehfar H.

Eur J Nucl Med Mol Imaging. 2017 Aug;44(9):1473-1479. doi: 10.1007/s00259-017-3681-9

 

German Multicenter Study Investigating ¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients.

Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schäfers M, Essler M, Baum RP, Kulkarni HR, Schmidt M, Drzezga A, Bartenstein P, Pfestroff A, Luster M, Lützen U, Marx M, Prasad V, Brenner W, Heinzel A, Mottaghy FM, Ruf J, Meyer PT, Heuschkel M, Eveslage M, Bögemann M, Fendler WP, Krause BJ.

J Nucl Med. 2017 Jan;58(1):85-90. doi: 10.2967/jnumed.116.183194.

 

Successful Treatment of Hepatic Metastases of Hormone Refractory Prostate Cancer Using Radioligand Therapy With ¹⁷⁷Lu-PSMA-617.

Wei X, Schlenkhoff C, Sopora C, Essler M, Ahmadzadehfar H.

Clin Nucl Med. 2016 Nov;41(11):894-895.

 

^{177Lu-PSMA-617 radioligand therapy of mCRPC: evaluation criteria of response.}

 

Rahbar K, Bögemann M, Ahmadzadehfar H.

 

Eur J Nucl Med Mol Imaging. 2017 Jan;44(1):166-167

 

 

Radioligand therapy with ¹⁷⁷Lu-PSMA-617 of metastatic prostate cancer has already been arrived in clinical use.

Ahmadzadehfar H, Essler M, Schäfers M, Rahbar K.

Nucl Med Biol. 2016 Dec;43(12):835. doi: 10.1016/j.nucmedbio.2016.08.003.

 

Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with ¹⁷⁷Lu-PSMA-617.

Ferdinandus J, Eppard E, Gaertner FC, Kürpig S, Fimmers R, Yordanova A, Hauser S, Feldmann G, Essler M, Ahmadzadehfar H.

J Nucl Med. 2017 Feb;58(2):312-319. doi: 10.2967/jnumed.116.178228.

 

 

[¹⁷⁷Lu-PSMA-617 therapy, dosimetry and follow-up in patients with metastatic castration-resistant prostate cancer].

 

Fendler WP, Kratochwil C, Ahmadzadehfar H, Rahbar K, Baum RP, Schmidt M, Pfestroff A, Lützen U, Prasad V, Heinzel A, Heuschkel M, Ruf J, Bartenstein P, Krause BJ.

Nuklearmedizin. 2016 Jun 28;55(3):123-8. German.

 

Response and Tolerability of a Single Dose of ¹⁷⁷Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: A Multicenter Retrospective Analysis.

 

Rahbar K, Schmidt M, Heinzel A, Eppard E, Bode A, Yordanova A, Claesener M, Ahmadzadehfar H.

 

J Nucl Med. 2016 Sep;57(9):1334-8. doi: 10.2967/jnumed.116.173757.

 

Metastatic Prostate Cancer With Restored Hormone-Response After Radioligand Therapy With ¹⁷⁷Lu-PSMA-617.

 

Schlenkhoff CD, Knüpfer E, Essler M, Ahmadzadehfar H.

 

Clin Nucl Med. 2016 Jul;41(7):572-3. doi: 10.1097/RLU.0000000000001200.

 

Positive Influence of ¹⁷⁷Lu PSMA-617 Therapy on Bone Marrow Depression Caused by Metastatic Prostate Cancer.

 

Schlenkhoff CD, Gaertner F, Essler M, Schmidt M, Ahmadzadehfar H.

 

Clin Nucl Med. 2016 Jun;41(6):478-80. doi: 10.1097/RLU.0000000000001195.

 

Therapeutic response and side effects of repeated radioligand therapy with ¹⁷⁷Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer.

 

Ahmadzadehfar H, Eppard E, Kürpig S, Fimmers R, Yordanova A, Schlenkhoff CD, Gärtner F, Rogenhofer S, Essler M.

 

Oncotarget. 2016 Mar 15;7(11):12477-88. doi: 10.18632/oncotarget.7245.

 

Early side effects and first results of radioligand therapy with ¹⁷⁷Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study.

 

Ahmadzadehfar H, Rahbar K, Kürpig S, Bögemann M, Claesener M, Eppard E, Gärtner F, Rogenhofer S, Schäfers M, Essler M.

 

EJNMMI Res. 2015 Dec;5(1):114. doi: 10.1186/s13550-015-0114-2.