177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

Yadav, Madhav P.; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant; Sahoo, Ranjit Kumar; Seth, Amlesh; Bal, Chandrasekhar

doi:10.1007/s00259-016-3481-7

Cited by 129 publications

(53 citation statements)

References 21 publications

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“…Indeed, serious adverse events for kidney or salivary gland function were not recorded, indicating an excellent safety profile of 177 Lu-PSMA-617 RLT. Consistent with dosimetry and previous clinical findings [14-17] the rate of hematologic adverse events was low and few hematologic conditions were transient and not life threatening.…”

Section: Discussionsupporting

confidence: 89%

Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer

et al. 2016

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Prostate cancer can be targeted by ligands to the prostate-specific membrane antigen (PSMA). We aimed to evaluate dosimetry, safety and efficacy of 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC).Fifteen patients each received two cycles of 3.7 GBq (n = 5) or 6.0 GBq (n = 10) 177Lu-PSMA-617 at an eight to ten weeks interval. For safety monitoring, each treatment was followed by dosimetry with serial quantitative SPECT as well as inpatient and outpatient recording of adverse events. Response to RLT was primarily determined by baseline to follow-up change in 68Ga-PSMA PET/CT (RECIST1.1), as well as change in prostate-specific antigen (PSA), quality of life (QoL, FACT-P scale), and pain (Brief Pain Inventory) as secondary endpoints.Radiation dose delivered to the tumor (6.1 Gy/GBq) was six to twelve-fold higher than to critical organs (kidney left/right 0.5/0.6 Gy/GBq each, salivary glands 1.0 Gy/GBq). Total radiation dose per kidney did not exceed 23 Gy in any patient. Three patients had sub-acute and latent grade 3 events, i.e. anemia, leukocytopenia, and nausea. No acute events, grade ≥4 events or high grade events for salivary gland or kidney function were observed. After two RLT cycles, 4 (27%) patients had partial response, 6 (40%) had stable disease, and 5 (33%) had progressive disease according to RECIST. Any PSA decline was observed in 12/15 (80%) patients during RLT. Significant pain relief was documented in 7/10 (70%) symptomatic patients and QoL improved in 9/15 (60%) patients.177Lu-PSMA-617 therapy proved safe and indicated promising response rates for both objective and patient-reported outcomes in our small group of mCRPC patients.

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Section: Discussionsupporting

confidence: 89%

Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer

et al. 2016

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“…Due to the high amount of ligand administered during scanning, it is possible that the ligand can residualize on the receptors and affect the quantification on the subsequent scan. With increasing use of [ 68 Ga]DP11 as a scouting scan for treatment with [ 177 Lu]DKFZ-PSMA-617 [15] or [ 225 Ac]DKFZ-PSMA-617 [16], it is important to understand the effect of prior imaging with [ 68 Ga]DP11 (if any) on the uptake of the therapeutic radiopharmaceutical.…”

Section: Introductionmentioning

confidence: 99%

Repeatability of [68Ga]DKFZ11-PSMA PET Scans for Detecting Prostate-specific Membrane Antigen-positive Prostate Cancer

et al. 2017

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Purpose We studied the effect of varying specific activity of [68Ga]DKFZ-PSMA11 ([68Ga]DP11) on repeated imaging of prostate-specific membrane antigen-positive (PSMA+) xenograft tumors. Procedures Athymic nude mice bearing PC3-PIP (PSMA+) and PC3 (PSMA−) bilateral flank tumors were assessed to study intra- and inter-day repeatability of [68Ga]DP11 imaging in mice administered [68Ga]DP11 or [67Ga]DP11 (as a dilution tracer) using imaging and biodistribution studies. Results Region-of-interest (ROI) analysis of the [68Ga]DP11 imaging study indicated that the uptake was constant on same day or consecutive days. Prior imaging with [68Ga]DP11 did not significantly influence the subsequent uptake of [68Ga]DP11. Uptake of [68Ga]DP11 (60 min) and [67Ga]DP11 (24 h) in PC3-PIP tumors was 12.37 ± 4.19 %ID/g and 12.49 ± 6.88 %ID/g, respectively; [68Ga]DP11 was 13.83 ± 3.77 and 17.76 ± 1.84 on same-day and 15.98 ± 5.82 %ID/g on second-day imaging. Conclusions This study demonstrates that [68Ga]DP11, in a given PSMA+ lesion, is constant under several same-day or serial-day imaging conditions.

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“…In addition, liver uptake was considerable 36. In contrast, clinical responses between 31-68% have been observed in initial trials with the reversible small-molecule 177 Lu-PSMA-617 with relatively low incidence of hematologic toxicity 29, 37, 38. Although the early human data are promising, short circulation time is a disadvantage for these small-molecule radiotherapies, particularly with respect to the 6.7-day half-life of Lu-177.…”

Section: Discussionmentioning

confidence: 99%

¹⁷⁷Lu-Labeled Phosphoramidate-Based PSMA Inhibitors: The Effect of an Albumin Binder on Biodistribution and Therapeutic Efficacy in Prostate Tumor-Bearing Mice

Choy¹,

Ling²,

Geruntho³

et al. 2017

Theranostics

100

171

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Prostate-specific membrane antigen (PSMA) continues to be an active biomarker for small-molecule PSMA-targeted imaging and therapeutic agents for prostate cancer and various non-prostatic tumors that are characterized by PSMA expression on their neovasculature. One of the challenges for small-molecule PSMA inhibitors with respect to delivering therapeutic payloads is their rapid renal clearance. In order to overcome this pharmacokinetic challenge, we outfitted a 177Lu-labeled phosphoramidate-based PSMA inhibitor (CTT1298) with an albumin-binding motif (CTT1403) and compared its in vivo performance with that of an analogous compound lacking the albumin-binding motif (CTT1401). The radiolabeling of CTT1401 and CTT1403 was achieved using click chemistry to connect 177Lu-DOTA-N3 to the dibenzocyclooctyne (DBCO)-bearing CTT1298 inhibitor cores. A direct comparison in vitro and in vivo performance was made for CTT1401 and CTT1403; the specificity and efficacy by means of cellular uptake and internalization, biodistribution, and therapeutic efficacy were determined for both compounds. While both compounds displayed excellent uptake and rapid internalization in PSMA+ PC3-PIP cells, the albumin binding moiety in CTT1403 conferred clear advantages to the PSMA-inhibitor scaffold including increased circulating half-life and prostate tumor uptake that continued to increase up to 168 h post-injection. This increased tumor uptake translated into superior therapeutic efficacy of CTT1403 in PSMA+ PC3-PIP human xenograft tumors.

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177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

Abstract: Lu-DKFZ-PSMA-617 radionuclide therapy is a safe and effective approach in the treatment of mCRPC patients.

Cited by 129 publications

References 21 publications

Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer

Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer

Repeatability of [68Ga]DKFZ11-PSMA PET Scans for Detecting Prostate-specific Membrane Antigen-positive Prostate Cancer

¹⁷⁷Lu-Labeled Phosphoramidate-Based PSMA Inhibitors: The Effect of an Albumin Binder on Biodistribution and Therapeutic Efficacy in Prostate Tumor-Bearing Mice

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177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

Abstract: Lu-DKFZ-PSMA-617 radionuclide therapy is a safe and effective approach in the treatment of mCRPC patients.

Cited by 129 publications

References 21 publications

Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer

Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer

Repeatability of [68Ga]DKFZ11-PSMA PET Scans for Detecting Prostate-specific Membrane Antigen-positive Prostate Cancer

177Lu-Labeled Phosphoramidate-Based PSMA Inhibitors: The Effect of an Albumin Binder on Biodistribution and Therapeutic Efficacy in Prostate Tumor-Bearing Mice

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¹⁷⁷Lu-Labeled Phosphoramidate-Based PSMA Inhibitors: The Effect of an Albumin Binder on Biodistribution and Therapeutic Efficacy in Prostate Tumor-Bearing Mice