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Year : 2020  |  Volume : 36  |  Issue : 1  |  Page : 69-70

The role of 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: Is it the new beginning

Department of Urology, AIIMS, Bhubaneswar, Odisha, India

Date of Submission11-Sep-2019
Date of Acceptance03-Nov-2019
Date of Web Publication2-Jan-2020

Correspondence Address:
Sumit Agrawal
Department of Urology, AIIMS, Bhubaneswar, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/iju.IJU_266_19

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How to cite this article:
Agrawal S. The role of 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: Is it the new beginning. Indian J Urol 2020;36:69-70

How to cite this URL:
Agrawal S. The role of 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: Is it the new beginning. Indian J Urol [serial online] 2020 [cited 2021 Aug 1];36:69-70. Available from:

   Summary Top

The treatment of metastatic castrate-resistant prostate cancer (mCRPC) includes abiraterone acetate, enzalutamide or docetaxel chemotherapy along with androgen ablation. However, the response to these agents is often short lived and not complete. Prostate-specific membrane antigen (PSMA) is overexpressed in metastatic prostate cancer and has been found to be a suitable target for imaging and therapy. The225 Actinium labeled derivative,225 Ac-PSMA-617, has shown a remarkable therapeutic efficacy in mCRPC patients.

Sathekge et al.[1] performed a study with a treatment group consisting of patients who relapsed after the initial therapy and presented with metastatic prostate carcinoma. Inclusion criteria included Eastern Cooperative Oncology Group score 2 or lower, a life expectancy of 6 months or more, widespread metastatic disease precluding treating with radiotherapy, patients' refusal of chemotherapy or hormonal therapy, and lack of access to second-generation anti-androgen therapy (abiraterone and enzalutamide). All patients underwent68 Ga-PSMA-11 positron-emission tomography/computed tomography (PET/CT) before225 Ac-PSMA-617 treatment to look if the lesions were PSMA avid.

The initial administered activity was 8 MBq. Administered activity was de-escalated in subsequent treatment cycles to 7, 6, or 4 MBq based on the response to earlier administered treatment and repeated after every 8 weeks. Response to the treatment was seen by serum prostate-specific antigen (PSA) and68 Ga-PSMA-PET/CT imaging. PSA was obtained at the beginning and then monthly, and68 Ga-PSMA-PET/CT was repeated every 8 weeks (before each subsequent cycle of treatments was administered) and every 12 weeks after completion of the treatment until disease progression.

Good antitumor activity as assessed by serum PSA level, and68 Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17 patients, PSA decline ≥ 90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7) or three cycles (5/7) cycles of225 Ac-PSMA-617. Fifteen of 17 patients had a >50% decline in lesions avidity for tracer on68 Ga-PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or resolution of lymph node metastases) of all metastatic lesions.[1] There were side effects in the form of xerostomia, bone marrow toxicity, and renal toxicity.

   Comments Top

The treatment of mCRPC is still evolving. This study gives options of using receptor-targeted therapy. Various agents used till date are tabulated in the following [Table 1].[2]
Table 1: Various studies and agents/drugs in the treatment of mCRPC

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PSMA-617 had been labeled with radioisotope Lu-117 (beta emitter) and Ac-225 (alpha emitter) for radioligand therapy. 225Ac-PSMA-617 is more effective for chemotherapy naïve mCRPC. These patients need to be under close scrutiny during treatment due to its toxicity to the liver, kidney, and bone marrow. In a similar earlier study by Kratochwil et al.,[3] 24 (63%) men had a PSA decline of more than 50% and 33 (87%) had a PSA response of any degree. The median duration of tumor control under 225Ac-PSMA-617 last-line therapy was 9.0 months, and five patients had an enduring response of more than 2 years.

Remission could be achieved with225 Ac-PSMA-617 (targeted alpha therapy) receptor ligand therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma. Remarkable therapeutic efficacy could be achieved with reduced toxicity to salivary glands due to a strategy of de-escalation of administered activities in the second and third treatment cycles. There is only a limited amount of presently available isotope and that too produced by only a few centers in the world.[4] The availability of the treatment and the cost is an issue.

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Conflicts of interest:

There are no conflicts of interest.

   References Top

Sathekge M, Bruchertseifer F, Knoesen O, Reyneke F, Lawal I, Lengana T, et al. 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: A pilot study. Eur J Nucl Med Mol Imaging 2019;46:129-38.  Back to cited text no. 1
Mottet N, Van Der Bergh RC, Briers E, Bourke L, Cornford, Santis MD, et al. EAU-ESTRO-ESUR- SIOG guidelines on prostate cancer 2018. p. 72-4  Back to cited text no. 2
Kratochwil C, Bruchertseifer F, Giesel FL, Weis M, Verburg FA, Mottaghy F, et al. 225Ac-PSMA-617 for PSMA-targeted α-radiation therapy of metastatic castration-resistant prostate cancer. J Nucl Med 2016;57:1941-4.  Back to cited text no. 3
Chakravarty R, Siamof CM, Dash A, Cai W. Targeted α-therapy of prostate cancer using radiolabeled PSMA inhibitors: A game changer in nuclear medicine. Am J Nucl Med Mol Imaging 2018;8:247-67.  Back to cited text no. 4


  [Table 1]


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