Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with 131I-MIP-1095

Abstract

PurposeProstate-specific membrane antigen (PSMA)-targeting radioligand therapy (RLT) was introduced in 2011. The first report described the antitumor and side effects of a single dose. The aim of this analysis was to evaluate toxicity and antitumor activity after single and repetitive therapies.MethodsThirty-four men with metastatic castration-resistant prostate cancer received PSMA-RLT with 131I-MIP-1095. Twenty-three patients received a second, and three patients a third dose, timed at PSA progression after an initial response to the preceding therapy. The applied doses were separated in three groups: <3.5, 3.5–5.0 and >5.0 GBq. Antitumor and side-effects were analyzed by blood samples and other clinical data. Follow-up was conducted for up to 5 years.ResultsThe best therapeutic effect was achieved by the first therapy. A PSA decline of ≥50% was achieved in 70.6% of the patients. The second and third therapies were significantly less effective. There was neither an association between the applied activity and PSA response or the time-to-progression. Hematologic toxicities were less prevalent but presented in a higher percentage of patients with increasing number of therapies. After hematologic toxicities, xerostomia was the second most frequent side effect and presented more often and with higher intensity after the second or third therapy.ConclusionThe first dose of RLT with 131I-MIP-1095 presented with low side effects and could significantly reduce the tumor burden in a majority of patients. The second and third therapies were less effective and presented with more frequent and more intense side effects, especially hematologic toxicities and xerostomia.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-017-3665-9) contains supplementary material, which is available to authorized users.

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

“…42,43 Figure S4), which are in agreement with other studies that have examined the binding of PSMA ligands to PSMA-positive cells. [44][45][46] Gourni et al showed that [ 11 In]In-PSMA-617 to LNCaP cells yielded a k d of 5.4 nM. 44 Umbricht et al reported that [ 177 Lu]Lu-PSMA-617, [ 44 Sc]Sc-PSMA-617 and [ 68 Ga] Ga-PSMA-617 to PC-3 PIP cells gave the k d values of 39, 33 and 72 nM, respectively.…”

“…The most studied PSMA ligands for therapeutic use, PSMA‐617 and PSMA‐I&T, have different linkers, while the binding motif (glutamate‐urea moiety) and the chelating moiety (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid [DOTA]) are the same. PSMA‐617 and PSMA‐I&T labelled with the beta emitter 177 Lu ( t 1/2 ≈6.7 days) and MIP‐1095 labelled with the beta emitter 131 I ( t 1/2 ≈8.0 days) have been investigated in preclinical and clinical studies . A recent meta‐analysis of 17 studies demonstrated that RLT with [ 177 Lu]Lu‐PSMA‐617 and [ 177 Lu]Lu‐PSMA‐I&T is an effective treatment for mCRPC with low toxicity .…”

“…PSMA-617 and PSMA-I&T labelled with the beta emitter 177 Lu (t 1/2 ≈6.7 days) and MIP-1095 labelled with the beta emitter 131 I (t 1/2 ≈8.0 days) have been investigated in preclinical and clinical studies. [7][8][9][10][11] A recent meta-analysis of 17 studies demonstrated that RLT with [ 177 Lu]Lu-PSMA-617 and [ 177 Lu]Lu-PSMA-I&T is an effective treatment for mCRPC with low toxicity. 10 However, around 30% of patients do not respond to [ 177 Lu]Lu-PSMA RLT.…”

The role of immune checkpoint inhibitors in prostate cancer

“…The most serious clinical problem is that in the course of treatment PC becomes refractory to hormone manipulation, known as metastatic castration-resistant prostate cancer (mCRPC) [2,4]. There are many options for the treatment of mCRPC including docetaxel, abiraterone acetate, enzalutamide, cabazitaxel, radium-223, Sipuleucel-T (the only cancer vaccine approved to treat advanced PC so far) [3,4,5,6,7,8], and radioligand therapy (RLT) directed against prostate-specific membrane antigen PSMA, which could be successfully used as a third line therapy of mCRPC [9,10,11].…”

A Single Dose of 225Ac-RPS-074 Induces a Complete Tumor Response in an LNCaP Xenograft Model

“…Ligands labeled with the b-emitting 177 Lu, such as 177 Lu-prostate-specific membrane antigen (PSMA) 617 (2)(3)(4)(5)(6) and 177 Lu-PSMA-I&T (7)(8), have been shown to induce at least a 50% decrease in PSA in 30%-60% of patients after a single cycle or multiple cycles of therapy, with only mild-to-moderate, reversible side effects evident even after multiple therapy cycles. Other ligands labeled with the b-emitting 131 I, such as 131 I-MIP-1095, have induced even more dramatic responses, though the reported side effects were more severe (9)(10).…”