Radioimmunotherapy of Metastatic Prostate Cancer with &lt;sup&gt;177&lt;/sup&gt;Lu-DOTAhuJ591 Anti Prostate Specific Membrane Antigen Specific Monoclonal Antibody

Vallabhajosula, Shankar; Nikolopoulou, Anastasia; Jhanwar, Yuliya; Kaur, Gurpreet; Tagawa, Scott T.; Nanus, David M.; Bander, Neil H.; Goldsmith, Stanley J.

doi:10.2174/1874471008666150313114005

Cited by 67 publications

(45 citation statements)

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“…4, a moderate depression of blood cell count was observed after each cycle with the nadir around 6 weeks post-therapy. PSMA RLT with the radiolabeled antibody 177 Lu-J591 resulted in comparable red marrow doses [9] and hematological toxicity as well as the platelet nadir are also in accordance with our results [28]. In contrast, with 177 Lu-PSMA-617, the red marrow dose is about 0.025–0.03 Gy/GBq [14, 29] and therapy with 6 GBq 177 Lu-PSMA-617 translates into an estimated red marrow dose of 0.15–0.2 Gy.…”

Section: Discussionsupporting

confidence: 90%

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

Afshar‐Oromieh

Haberkorn

Zechmann

et al. 2017

Eur J Nucl Med Mol Imaging

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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.

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Section: Discussionsupporting

confidence: 90%

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

Afshar‐Oromieh

Haberkorn

Zechmann

et al. 2017

Eur J Nucl Med Mol Imaging

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“…The slow diffusion of antibodies into solid lesions, with an uptake maximum at 6 or 7 d after injection, and hematotoxicity caused by a long circulation time in blood are significant limitations of radiolabeled antibody therapy (108). Small-molecule PSMA ligands for endoradiotherapy were first used by Zechmann et al, who treated 28 mCRPC patients with a single therapeutic dose of 131 I-MIP-1095 (mean activity, 4.8 GBq; range, 2-7.2 GBq) (65).…”

Section: Psma Ligand-based Therapeutic Applications Radionuclide Therapymentioning

confidence: 99%

Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy

et al. 2017

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The prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PC) cells. Therefore, the targeting of PSMA has become increasingly important over the last decade. Glu-ureabased PSMA ligands used for both imaging and radioligand therapy are the mainstays of the current success. For PET imaging, both 68 Gaand 18 F-labeled agents have been successfully translated to clinical applications. Mainly retrospective cohort studies have shown a high value in the setting of biochemical recurrence, with high detection rates even in the presence of low prostate-specific antigen levels. Preliminary data indicated that radioguided surgery with PSMA ligands may help to further improve patient outcomes because it facilitates the removal of small tumor deposits that are otherwise difficult to detect. For primary PC, PSMA ligand PET imaging has been shown to be superior to cross-sectional imaging for the detection of metastatic lymph nodes. In addition, it promises to also provide intraprostatic tumor localization, especially when used in combination with multiparametric MRI. Increasing numbers of studies have reported considerable changes in management resulting from PSMA ligand PET imaging for both biochemical recurrence and primary disease. The use of 177 Lu-PSMA-based radioligand therapy has demonstrated a reasonable response, mainly as defined by a prostate-specific antigen response of more than 50%, comparable to other recently introduced agents. Especially given the high level of safety of 177 Lu-PSMA radioligand therapy, with only minimal grade 3 and 4 toxicities reported so far, it has the potential to expand options for metastatic castrationresistant PC. This review is intended to provide a comprehensive overview of the current literature on low-molecular-weight PSMA ligands for both PET imaging and therapeutic approaches, with a focus on agents that have been clinically adopted.

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“…As an imaging tracer, mAb J591 linked to radionuclides 89 Zr or 111 I gave excellent results in the detection of bone lesions [49, 50]. mAb J591 linked to 177 Lu was used in radio-immunotherapy to successfully target circulating tumor cells [20, 31]. mAb J591 was used to deliver the cytotoxic drug maytansinoid-1 (DM1) in a phase I clinical trial [21].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, a therapeutic entity can be coupled to a PSMA ligand and internalized into prostate cancer cells. Indeed, a variety of PSMA-targeting ligands are being investigated for tumor imaging [25–27] and for the development of PSMA-targeted therapeutic agents [28–31]. …”

Section: Introductionmentioning

confidence: 99%

PSMA-homing dsRNA chimeric protein vector kills prostate cancer cells and activates anti-tumor bystander responses

et al. 2017

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The treatment of metastatic androgen-resistant prostate cancer remains a challenge. We describe a protein vector that selectively delivers synthetic dsRNA, polyinosinic/polycytidylic acid (polyIC), to prostate tumors by targeting prostate specific membrane antigen (PSMA), which is overexpressed on the surface of prostate cancer cells.The chimeric protein is built from the double stranded RNA (dsRNA) binding domain of PKR tethered to a single chain anti-PSMA antibody. When complexed with polyIC, the chimera demonstrates selective and efficient killing of prostate cancer cells. The treatment causes the targeted cancer cells to undergo apoptosis and to secrete toxic cytokines. In a bystander effect, these cytokines kill neighboring cancer cells that do not necessarily overexpress PSMA, and activate immune cells that enhance the killing effect. The strong effects of the targeted polyIC are demonstrated on both 2D cell cultures and 3D tumor spheroids.

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Radioimmunotherapy of Metastatic Prostate Cancer with <sup>177</sup>Lu-DOTAhuJ591 Anti Prostate Specific Membrane Antigen Specific Monoclonal Antibody

Cited by 67 publications

References 0 publications

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

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

Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy

PSMA-homing dsRNA chimeric protein vector kills prostate cancer cells and activates anti-tumor bystander responses

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