PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports

• Published in: European journal of nuclear medicine and molecular imaging 2021-12, Vol.48 (13), p.4350-4368
• Main Authors: Uijen, M. J. M., Derks, Y. H. W., Merkx, R. I. J., Schilham, M. G. M., Roosen, J., Privé, B. M., van Lith, S. A. M., van Herpen, C. M. L., Gotthardt, M., Heskamp, S., van Gemert, W. A. M., Nagarajah, J.
• Format: Article
• Language: English
• Subjects: Antigens; Brain cancer; Breast cancer; Cardiology; Computed tomography; Dipeptides; Glioblastoma; Hepatocellular carcinoma; Heterocyclic Compounds, 1-Ring; Humans; Imaging; Immunohistochemistry; Kidney cancer; Lung cancer; Lung carcinoma; Lutetium isotopes; Male; Medical imaging; Medicine; Medicine & Public Health; Nuclear Medicine; Oncology; Oncology – General; Oral cancer; Orthopedics; Patients; Positron emission; Positron Emission Tomography Computed Tomography; Prostate cancer; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - radiotherapy; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radiology; Renal cell carcinoma; Review; Review Article; Salivary gland; Salivary glands; Side effects; Solid tumors; Therapy; Thyroid cancer; Tomography; Tumors
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-021-05433-w

In the past decade, a growing body of literature has reported promising results for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy in prostate cancer. First clinical studies evaluating the efficacy of [ 177 Lu]Lu-PSMA radioligand therapy (PSMA-RLT) demonstrated favorable results in prostate cancer patients. [ 177 Lu]Lu-PSMA is generally well tolerated due to its limited side effects. While PSMA is highly overexpressed in prostate cancer cells, varying degrees of PSMA expression have been reported in other malignancies as well, particularly in the tumor-associated neovasculature. Hence, it is anticipated that PSMA-RLT could be explored for other solid cancers. Here, we describe the current knowledge of PSMA expression in other solid cancers and define a perspective towards broader clinical implementation of PSMA-RLT. This review focuses specifically on salivary gland cancer, glioblastoma, thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, lung cancer, and breast cancer. An overview of the (pre)clinical data on PSMA immunohistochemistry and PSMA PET/CT imaging is provided and summarized. Furthermore, the first clinical reports of non-prostate cancer patients treated with PSMA-RLT are described.