Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting radiopharmaceutical into the circulation of a patient. The radiopharmaceutical will bind to a specific peptide receptor leading to tumor-specific binding and retention. The only target that is currently used in clinical practice is the somatostatin receptor (SSTR), which is overexpressed on a range of tumor cells, including neuroendocrine tumors and neural-crest derived tumors. Academia played an important role in the development of PRRT, which has led to heterogeneous literature over the last two decades, as no standard radiopharmaceutical or regimen has been available for a long time. This review provides a summary of the treatment efficacy (e.g., response rates and symptom-relief), impact on patient outcome and toxicity profile of PRRT performed with different generations of SSTR-targeting radiopharmaceuticals, including the landmark randomized-controlled trial NETTER-1. In addition, multiple optimization strategies for PRRT are discussed, i.e., the dose–effect concept, dosimetry, combination therapies (i.e., tandem/duo PRRT, chemoPRRT, targeted molecular therapy, somatostatin analogues and radiosensitizers), new radiopharmaceuticals (i.e., SSTR-antagonists, Evans-blue containing vector molecules and alpha-emitters), administration route (intra-arterial versus intravenous) and response prediction via molecular testing or imaging. The evolution and continuous refinement of PRRT resulted in many lessons for the future development of radionuclide therapy aimed at other targets and tumor types.

Background: Detection of the site of recurrence using PSMA-PET/CT is important to guide treatment in patients with biochemical recurrence of prostate cancer (PCa). The aim of this study was to evaluate the positivity rate of [¹⁸F]PSMA-1007-PET/CT in patients with biochemically recurrent PCa and identify parameters that predict scan positivity as well as the type and number of detected lesions. This monocentric retrospective study included 137 PCa patients with biochemical recurrence who underwent one or more [¹⁸F]PSMA-1007-PET/CT scans between August 2018 and June 2019. PET-positive malignant lesions were classified as local recurrence, lymph node (LN), bone or soft tissue lesions. The association between biochemical/paraclinical parameters, as PSA value, PSA doubling time, PSA velocity, Gleason score (GS) and androgen deprivation therapy (ADT), and scan positivity as well as type and number of detected lesions was evaluated using logistic regression analysis (binary outcomes) and Poisson models (count-type outcomes). Results: We included 175 [¹⁸F]PSMA-1007-PET/CT scans after radical prostatectomy (78%), external beam radiation therapy (8.8%), ADT (7.3%), brachytherapy (5.1%) and high intensity focused ultrasound (0.7%) as primary treatment (median PSA value 1.6 ng/ml). Positivity rate was 80%. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence of bone and soft tissue lesions and number of bone, LN and soft tissue lesions, both in uni- and/or multivariable analysis. Multivariable analysis also showed prior ADT as predictor of bone and soft tissue lesions, GS as predictor of the number of bone lesions and ongoing ADT as predictor of the number of LN lesions. Conclusion: [¹⁸F]PSMA-1007-PET/CT showed a high positivity rate in patients with biochemically recurrent PCa. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence and number of bone and soft tissue lesions and the number of LN lesions. Our findings can guide clinicians in optimal patient selection for [¹⁸F]PSMA-1007-PET/CT and support further research leading to the development of a prediction nomogram.

In this chapter, we address the role of radiation as treatment modality in the context of oncological treatments given to patients. Physical aspects of the use of ionizing radiation (IR)—by either photons, neutrons, or charged (high linear energy transfer) particles—and their clinical application are summarized. Information is also provided regarding the radiobiological rationale of the use of conventional fractionation as well as alternative fractionation schedules using deviating total dose, fraction size, number of fractions, and the overall treatment time. Pro- and contra arguments of hypofractionation are discussed. In particular, the biological rationale and clinical application of Stereotactic Body Radiation Therapy (SBRT) are described. Furthermore, background information is given about FLASH radiotherapy (RT), which is an emerging new radiation method using ultra-high dose rate allowing the healthy, normal tissues and organs to be spared while maintaining the antitumor effect. Spatial fractionation of radiation in tumor therapy, another method that reduces damage to normal tissue is presented. Normal tissue doses could also be minimized by interstitial or intraluminal irradiation, i.e., brachytherapy, and herein an overview is given on the principles of brachytherapy and its clinical application. Furthermore, details are provided regarding the principles, clinical application, and limitations of boron neutron capture therapy (BNCT). Another important key issue in cancer therapy is the combination of RT with other treatment modalities, e.g., chemotherapy, targeted therapy, immunotherapy, hyperthermia, and hormonal therapy. Combination treatments are aimed to selectively enhance the effect of radiation in cancer cells or to trigger the immune system but also to minimize adverse effects on normal cells. The biological rationale of all these combination treatments as well as their application in clinical settings are outlined. To selectively reach high concentrations of radionuclides in tumor tissue, radioembolization is a highly interesting approach. Also, radioligand therapy which enables specific targeting of cancer cells, while causing minimal harm surrounding healthy tissues is presented. A brief overview is provided on how nanotechnology could contribute to the diagnosis and treatment of cancer. Last but not least, risk factors involved in acquiring secondary tumors after RT are discussed.

An 87-year-old man, without significant history, presented at the emergency department with recurrent episodes of fever and weight loss for several weeks without diagnosis, despite extensive routine investigations including conventional imaging. ¹⁸F-FDG PET/CT revealed strongly increased uptake in the peripheral vessels of the upper and lower limbs with relative sparing of the larger vessels. Temporal artery biopsy was positive for arteritis. The diagnosis of giant cell arteritis with mainly involvement of upper and lower limbs was made, and treatment with high-dose oral methylprednisolone was started, resulting in a rapid clinical and biochemical improvement.