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To date, several papers have been published about prostate-specific membrane antigen (PSMA)-based radioligand diagnostic and therapeutic approaches. This paper mainly provides information for nuclear medicine physicians that are clinically engaged in the diagnosis and treatment of prostate cancer patients. It aims to present the utility of PSMA imaging and therapy in a step-by-step practical approach; thus, it does not discuss radiochemistry and the molecular basics of PSMA.

Peptide receptor radionuclide therapy (PRRT) is a very effective treatment modality for advanced neuroendocrine tumors (NETs), representing a teaching model for truly targeted antitumor therapy. With the growing cumulative evidence of PRRT in various treatment settings, we are witnessing increased perception of this modality as a potent treatment option in advanced disease. Although most data derives from retrospective analyses, results from prospective comparative evaluations, such as the NETTER-1 trial, are eagerly awaited and should help to raise PRRT to a higher level of evidence. At the same time, as increased levels of evidence are anticipated by prospective evaluations, further methodological improvements are going on in different ways and aspects of radionuclide therapy, mainly regarding the radiopharmaceuticals, the combination with other radionuclides or cytotoxic drugs, and the route of administration. Although diversity of PRRT increases—not supporting cumulative evidence as opposed to uniform treatment—it is very likely to achieve significant increase of efficacy by these efforts in the near future. As the intraarterial administration of PRRT agents in liver-dominant metastatic disease has the potential to improve outcome, it would have to be shown as to which patients would benefit from this approach, to what extent the benefit would be, and to when it would justify the increased efforts for patients and treating institutes. The approach of combining cytotoxic or radiosensitizing drugs with the PRRT agents seems to trigger a major boost of efficacy in pancreatic NET. The midterm future would show the extent of benefit in terms of long-term outcome and would probably lead to inclusion into clinical routine for this particular NET entity. The translation of somatostatin-receptor antagonists into human application represents another major source of significant improvement in terms of PRRT’s benefit-toxicity ratio. Eventually, it may not be completely unlikely to see another radiopharmaceutical being regarded as the PRRT agent of choice in the midterm future.

The prognosis of patients with surgically unresectable differentiated thyroid tumors deteriorates significantly if radioiodine therapy is or becomes ineffective, considering the limited role of conventional chemotherapies in these patients. Several alternative approaches have been investigated for the treatment of patients with advanced thyroid malignancies in recent years. Among targeted therapies, tyrosine kinase inhibitors have resulted in the most encouraging responses and could soon be, along with redifferentiation therapy, the possible palliative strategies. Radiopeptide therapy, especially with beta emitter-labeled DOTANOC, which shows a great affinity to the somatostatin receptors expressed by thyroid tumor cells, might also be an attractive approach considering its comparatively low rate of side effects. However, the indication should be evaluated on individual basis. Medullary thyroid carcinoma shows a worse overall prognosis compared with the other differentiated thyroid tumors especially because of its natural resistance to radioiodine therapy. However, among possible palliative strategies, 131 I-meta-iodobenzylguanidine therapy is a noteworthy therapeutic approach in patients experiencing metastasized medullary thyroid carcinoma. In summary, recent developments in the treatment of patients with advanced thyroid malignancies have shown promising results, raising the hope for better outcomes in these patients in future.

Radioembolization (RE), also termed selective internal radiation therapy (SIRT), has been gradually introduced to the clinical arsenal of cytoreductive modalities in recent years. There is growing evidence for efficiency in liver tumors of various entities, with the most prominent ones being hepatocellular carcinoma, colorectal cancer, and neuroendocrine tumors. Hepatic metastases of numerous other tumor entities including breast cancer, cholangiocarcinoma, and pancreatic cancer are treatment-sensitive, even when being refractory to other treatment modalities such as bland-embolization, regional, or systemic chemotherapy. The antitumor effect of SIRT is related to radiation rather than embolization, with extraordinary high local radiation doses obtained selectively at the site of viable tumor and little affection of the surrounding normal liver tissue. Morphologic changes after RE may pose difficulties for interpretation in conventional restaging with regard to tumor viability and true response to treatment. Therefore, functional imaging, that is, metabolic imaging with 18 F fluorodeoxyglucose positron emission tomography (computed tomography) in the majority of treated tumors, is regarded the gold standard in this respect and should be included for pre- and post-SIRT assessment. To prevent serious toxicity to be associated with the potent antitumor efficacy, meticulous pretreatment evaluation is of particular importance. Improvements in predicting dosimetry will help optimize treatment and patient selection. Nuclear medicine procedures are essential for planning, performing, and monitoring of RE. However, the interdisciplinary aspect of patient management has to be emphasized for this particular treatment form. As SIRT is moving forward from the salvage setting indication to the use in earlier stages of hepatic tumor disease and with the advent of new treatment protocols and targeted therapies, embedding SIRT into a multidisciplinary approach will become even more important. This article focuses on procedural and technical aspects for selection, preparation, and performance of treatment as well as post-therapeutic monitoring and response assessment.