Lutetium-177-PSMA-617: A Vision of the Future

Chandran, Elias; Figg, William D.; Madan, Ravi A.

doi:10.1080/15384047.2022.2037985

Cited by 19 publications

(20 citation statements)

References 27 publications

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“…As results of larger multi-center clinical trials on therapeutic agents such as Luthathera ® and Pluvicto ® [designed to selectively target tumors overexpressing somatostatin receptors or prostate specific membrane antigen (PSMA), respectively] become available, they are expanding our understanding of radionuclide therapy [ 68 , 69 ]. It is now well established that these agents prolong overall survival in patients affected by neuroendocrine tumors or prostate carcinoma; unfortunately, they fail to completely eradicate the disease.…”

Section: Discussionmentioning

confidence: 99%

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry

2023

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The β− emitter, rhenium-188 (188Re), has long been recognized as an attractive candidate for targeted cancer radionuclide therapy (TRNT). This transition metal shares chemical similarities with its congener element technetium, whose nuclear isomer technetium-99m (99mTc) is the current workhorse of diagnostic nuclear medicine. The differences between these two elements have a significant impact on the radiolabelling methods and should always receive critical attention. This review aims to highlight what needs to be considered to design a successful radiopharmaceutical incorporating 118Re. Some of the most effective strategies for preparing therapeutic radiopharmaceuticals with 188Re are illustrated and rationalized using the concept of the inorganic functional group (core) and a simple ligand field theoretical model combined with a qualitative definition of frontiers orbitals. Of special interest are the Re(V) oxo and Re(V) nitrido functional groups. Suitable ligands for binding to these cores are discussed, successful clinical applications are summarized, and a prediction of viable future applications is presented. Rhenium-188 decays through the emission of a high energy beta particle (2.12 MeV max energy) and a half-life of 16.9 h. An ideal biological target would therefore be a high-capacity target site (transporters, potential gradients, tumour microenvironment) with less emphasis on saturable targets such as overexpressed receptors on smaller metastases.

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Section: Discussionmentioning

confidence: 99%

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry

2023

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“…PSMA (prostate-specific membrane antigen) ligands are rapidly entering the diagnostic and therapeutic landscape of prostate cancer (Table 1 ). PSMA is also expressed in the lacrimal glands, which results in dry eyes in 30-40% of patients who are exposed to PSMA-targeted radioligands [ 115 , 116 ].…”

Section: Reviewmentioning

confidence: 99%

Potential Ophthalmological Side Effects Induced by Anti-Neoplastic Regimens for the Treatment of Genitourinary Cancers: A Review

Sakellakis¹,

Spathas²,

Tsaousis³

et al. 2022

Cureus

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The outcomes of patients with genitourinary (GU) cancers have been steadily improving in recent years. Novel therapies have entered our armamentarium, while several other regimens are currently being studied in clinical trials. This recent explosion of new agents has improved patient survival and the quality of life for patients, but has also significantly increased the frequency of several side effects. The current review will focus on the potential ocular adverse reactions of GU neoplastic treatments. The broad spectrum of manifestations of ocular toxicity underscores the uniqueness and complexity of the anatomic, physiologic, and metabolic features of the human eye. Most side effects are mild in severity and transient, but some can be severe, disabling, and irreversible. Clinicians should be aware of complications that might be vision threatening and impact the patient's quality of life. In this review, we focused on the ocular toxicity of the antineoplastic regimens that are currently used for the treatment of GU, including prostate cancer, bladder cancer, renal cell carcinoma, testicular cancer, pheochromocytoma, adrenocortical carcinoma, and penile cancer.

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“…Nevertheless, robust, randomized, and larger-scale trials are still required to thoroughly delineate the safety, efficacy, and optimal sequencing of 177 Lu-PSMA-617 therapy in the treatment landscape of mCRPC. [3,4] Lymphocytes play a significant role in anti-tumor immunity at all stages of cancer by triggering apoptosis and inhibiting the proliferation and migration of tumor cells. [5] Similarly, as a part of the innate immune system, neutrophils, monocytes, and platelets act as the primary line of defense, and respond to carcinogenic threats.…”

Section: Introductionmentioning

confidence: 99%

Prognostic role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, and pan-immune-inflammation value in metastatic castration-resistant prostate cancer patients who underwent 177Lu–PSMA-617

Şahin,

Kefeli,

Zorlu

et al. 2023

Medicine

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This study is aimed to investigate the prognostic significance of inflammation indices, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV) in metastatic castration-resistant prostate cancer (mCRPC) patients who had received lutetium labeled prostate-specific membrane antigen (177Lu–PSMA-617) therapy. Sixty-one mCRPC patients who received 177Lu–PSMA-617 treatment and followed up in Kocaeli University were included. The relationship between overall survival (OS) and progression-free survival (PFS) and clinical and laboratory parameters was analyzed by multivariate analyses. The mean age was 69.8 ± 6.9 years. The mean follow-up time was 53.2 ± 24 months. The median OS was 14 (95% CI: 8.8–18.1) and the median PFS was 10.4 (95% CI: 4.7–17.2) months. NLR ≥ 2.7, PLR ≥ 134.27, SII ≥ 570.39, PIV ≥ 408.59 were considered as elevated levels. In the multivariate analysis for OS, baseline ECOG performance score (HR: 1.92, 95% CI: 1.01–3.65, P = .046), high albümin (HR: 0.36, 95% CI: 0.16–0.82, P = .015), primary resistant total prostate-specific-antigen (PSA) (HR: 4.37, 95% CI: 1.84–10.35, P = .001), high NLR (HR: 3.32, 95% CI: 1.66–6.65, P = .001), high MLR (HR: 2.53, 95% CI: 1.35–4.76, P = .004), high PLR (HR: 2.47, 95% CI: 1.23–4.96, P = .01), and high SII (HR: 2.17, 95% CI: 1.09–4.32, P = .027) were associated with shorter OS. However, PIV was not associated with survival (P = .69). No factor other than the primer-resistant PSA could be identified as having an impact on PFS (for the PSA, HR: 4.52, 95% CI: 1.89–10.76, P = .001). In this study, pretreatment NLR, MLR, PLR, and SII demonstrate as powerful independent prognostic indices predicting survival in patients with mCRPC receiving 177Lu–PSMA-617 therapy.

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Lutetium-177-PSMA-617: A Vision of the Future

Cited by 19 publications

References 27 publications

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry

Potential Ophthalmological Side Effects Induced by Anti-Neoplastic Regimens for the Treatment of Genitourinary Cancers: A Review

Prognostic role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, and pan-immune-inflammation value in metastatic castration-resistant prostate cancer patients who underwent 177Lu–PSMA-617

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