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, Anna; Becker, A.; Eppard, Elisabeth; Kürpig, Stefan; Fisang, C.; Feldmann, Georg; Essler, Markus; Ahmadzadehfar, Hojjat

doi:10.1007/s00259-017-3681-9

Cited by 113 publications

(87 citation statements)

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“…The radiolabeling, administration, and treatment procedures in this study were conducted using previously described methods . The median administered activity per cycle was 6.2 GBq (total range of 3.2‐7.5 GBq).…”

Section: Methodsmentioning

confidence: 99%

“…However, PSMA‐RLT is still considered a last‐line treatment option, as data from prospective randomized phase III trials are lacking . According to recent studies, PSMA‐RLT seems to be safe and effective, even for patients with advanced PC or multiple PC relapses following several therapies . In the literature, the typical length of time that patients live posttreatment ranges between 7.5 and 15 months …”

Section: Introductionmentioning

confidence: 99%

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The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

et al. 2019

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Background Currently, prostate‐specific membrane antigen‐radioligand therapy (PSMA‐RLT) is considered a last‐line treatment option in advanced castration‐resistant prostate cancer. Despite these patients' poor prognosis, accurate estimation of their overall survival (OS) is essential to determine whether benefits exist from the treatment and whether the loss of valuable time and unnecessary side effects can be avoided. The aim of the present study is to evaluate whether various biochemical markers can predict OS in men undergoing PSMA‐RLT and whether the changes assessed after PSMA‐RLT correlate with the OS. Methods The tested tumor markers in this retrospective analysis were alkaline phosphatase (ALP), bone‐specific alkaline phosphatase (BAP), prostate‐specific antigen (PSA), lactate dehydrogenase (LDH), chromogranin A, and pro‐gastrin‐releasing peptide (pro‐GRP). For the evaluation, we performed blood tests before each PSMA‐RLT cycle and during follow‐up visits (which were 2‐3 months apart). All patients were followed up until their deaths. To test the correlations between the tumor markers and survival, we conducted the logrank tests and the multivariate Cox proportional‐hazards regression model. The significance level was set at P < .05. Results The study included 137 patients who received a total of 487 PSMA‐RLT cycles between January 2015 and November 2017. Of the tested biochemical tumor markers, baseline ALP (120 U/L cut‐off), LDH (248 U/L cut‐off), and PSA (first quartile cut‐off) correlated significantly with survival post‐PSMA‐RLT (P < .001 for ALP and LDH, and P = .007 for PSA). Stable and/or decreased values in most of the initially abnormal parameters were associated with significantly better OS; these parameters were ALP (P = .009), LDH (P = .005), PSA (P < .001), and pro‐GRP (P = .013). The BAP and ALP responses also correlated significantly with survival in patients with bone metastases (P = .002 and P < .001, respectively). Furthermore, there was a strong correlation of the kinetic patterns of PSA, ALP, BAP, and LDH with the survival, showing that patients with steadily increasing markers had the shortest OS. Conclusion Along with the established tumor marker PSA, ALP, LDH, BAP, and pro‐GRP were correlated with the OS post‐PSMA‐RLT in the univariate and multivariate analyses.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

et al. 2019

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“…The kidneys are a possible dose‐limiting organ because of the predominant renal excretion of PSMA ligands . The high uptake of 177 Lu‐ and 225 Ac‐labelled PSMA ligands in kidneys is usually observed short time (1‐4 hours) after injection of the radioligands, in both mice and humans .…”

Section: Introductionmentioning

confidence: 99%

“…25 The kidneys are a possible dose-limiting organ because of the predominant renal excretion of PSMA ligands. 26 The high uptake of 177 Lu-and 225 Ac-labelled PSMA ligands in kidneys is usually observed short time (1-4 hours) after injection of the radioligands, in both mice and humans. 27,28 With shorter-lived radionuclides like 212 Pb (t 1/2 ≈10.6 hours) and 211 At (t 1/2 ≈7.2 hours), the initial kidney uptake could represent a potential toxicity problem since a high dose will be delivered to the kidneys within the first few hours.…”

Section: Introductionmentioning

confidence: 99%

Preparation of the alpha‐emitting prostate‐specific membrane antigen targeted radioligand [²¹²Pb]Pb‐NG001 for prostate cancer

Stenberg

Juzeniene

Chen³

et al. 2020

Labelled Comp Radiopharmac

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Prostate‐specific membrane antigen (PSMA) is the most promising target for radioligand therapy of prostate cancer. The aim of this study was to prepare a small molecular ligand p‐SCN‐Bn‐TCMC‐PSMA (NG001) and compare it with the commonly used DOTA‐based PSMA‐617. The PSMA‐targeting ability of the 212Pb‐labelled ligands was evaluated using PSMA‐positive C4‐2 human prostate cancer cells. Lead‐212 is an in vivo generator of alpha particles by its daughter nuclides 212Bi and 212Po. NG001 was synthesized by conjugating the isothiocyanato group of p‐SCN‐Bn‐TCMC to the amino group of a glutamate‐urea‐based PSMA‐binding entity. Molecular size, chelator unit and chelator linking method are different in NG001 and PSMA‐617. Both ligands were efficiently labelled with 212Pb using a 224Ra/212Pb‐solution generator in transient equilibrium with progeny. Lead‐212‐labelled NG001 was purified with a yield of 85.9±4.7% and with 0.7±0.2% of 224Ra. Compared with [212Pb]Pb‐PSMA‐617, [212Pb]Pb‐NG001 displayed a similar binding and internalization in C4‐2 cells, with comparable tumour uptake in mice bearing C4‐2 tumours, but almost a 2.5‐fold lower kidney uptake. Due to the rapid normal tissue clearance and tumour cell internalization, any significant translocalization of 212Bi was not detected in mice. In conclusion, the obtained results warrant further preclinical studies to evaluate the therapeutic efficacy of [212Pb]Pb‐NG001.

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“…Recent studies have shown no evidence of grade 3/4 toxicity in patients with neuroendocrine tumors after repeated (≥8 cycles) radiopeptide therapy with a cumulative dose of up to 97 GBq 12. Good tolerability has also been observed in patients with prostate cancer (PC) after a cumulative dose of 36 GBq and up to six cycles of radioligand therapy 13,14…”

Section: Introduction: Goals Of Theranostics In Nuclear Medicinementioning

confidence: 99%

Theranostics in nuclear medicine practice

Yordanova¹,

Eppard²,

Kürpig³

et al. 2017

OTT

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190

115

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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.

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

Abstract: Renal toxicity in patients treated with [Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity.

Cited by 113 publications

References 19 publications

The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

Preparation of the alpha‐emitting prostate‐specific membrane antigen targeted radioligand [²¹²Pb]Pb‐NG001 for prostate cancer

Theranostics in nuclear medicine practice

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

Abstract: Renal toxicity in patients treated with [Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity.

Cited by 113 publications

References 19 publications

The value of tumor markers in men with metastatic prostate cancer undergoing [177Lu]Lu‐PSMA therapy

The value of tumor markers in men with metastatic prostate cancer undergoing [177Lu]Lu‐PSMA therapy

Preparation of the alpha‐emitting prostate‐specific membrane antigen targeted radioligand [212Pb]Pb‐NG001 for prostate cancer

Theranostics in nuclear medicine practice

Contact Info

Product

Resources

About

The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

Preparation of the alpha‐emitting prostate‐specific membrane antigen targeted radioligand [²¹²Pb]Pb‐NG001 for prostate cancer