Molecular alterations in malignant disease result in the expression or upregulations of various targets that can be used for imaging and treatment with radiopharmaceuticals. This theranostic principle has acquired greater importance in personalized medicine in recent years, particularly in oncology, where advanced tumors can be treated effectively with low side effects. Since the pioneering use of ¹³¹I in differentiated thyroid cancer in the 1940s, remarkable achievements in nuclear medicine endoradiotherapy have been demonstrated, mainly in the treatment of neuroendocrine neoplasms by using ¹⁷⁷Lu-labeled somatostatin analogs or in the treatment of advanced prostate cancer using prostate-specific membrane antigen–directed radionuclide therapy. Besides that, this review focuses on promising novel radiopharmaceuticals and describes their preclinical and clinical status. Radiolabeled antibodies, such as ¹³¹I-omburtamab directed against the B7-H3 protein on the surface of neuroblastoma cells; HuMab-5B1, a ⁸⁹Zr/¹⁷⁷Lu-labeled antibody for the treatment of CA19-9–expressing malignancies; and ¹⁷⁷Lu-lilotomab, a CD37 antibody for the treatment of B-cell lymphomas, are being highlighted. The neurotensin receptor ligand ¹¹¹In/¹⁷⁷Lu-3B-227 has demonstrated high potential in imaging and therapy for several malignancies (e.g., pancreatic adenocarcinomas). Targeting of the fibroblast activation protein is currently being explored for different tumor entities using PET imaging with the fibroblast activation protein inhibitor (FAPI) ⁶⁸Ga-FAPI-04, and the first therapeutic applications of ⁹⁰Y-FAPI-04 have been applied. After 2 decades of rapid development in theranostics, a variety of new targets are available for further clinical investigation.

Cancer has remained a formidable challenge in medicine and has claimed an enormous number of lives worldwide. Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer. This review aims to provide an overview of theranostics in oncology: exploring its history, current advances, challenges, and prospects. We present the fundamental evolution of theranostics from radiotherapeutics, cellular therapeutics, and nanotherapeutics, showcasing critical milestones in the last decade. From the early concept of targeted drug delivery to the emergence of personalized medicine, theranostics has benefited from advances in imaging technologies, molecular biology, and nanomedicine. Furthermore, we emphasize pertinent illustrations showcasing that revolutionary strategies in cancer management enhance diagnostic accuracy and provide targeted therapies customized for individual patients, thereby facilitating the implementation of personalized medicine. Finally, we describe future perspectives on current challenges, emerging topics, and advances in the field.

Our previous study has demonstrated the feasibility of noninvasive imaging of fibroblast activation protein (FAP)-expression after myocardial infarction (MI) in MI-territory in a rat model with ⁶⁸Ga-FAPI-04-PET. In the current extended clinical case, we sought to delineate cardiac uptake of ⁶⁸Ga-FAPI-04 in a patient after MI with clinical indication for the evidence of fibroblast activation. Carcinoma patients without cardiac disease underwent ⁶⁸Ga-FAPI-04-PET/CT as control. The patient with one-vessel disease underwent dynamic ⁶⁸Ga-FAPI-04-cardiac-PET/CMR for 60 minutes. Correlation of cardiac ⁶⁸Ga-FAPI-04 uptake with clinical findings, ECG, echocardiography, coronary-arteriography and enhanced cardiac-MRI with T1 MOLLI and ECV mapping were performed. No uptake was found in normal myocardium and in mature scar. A focal intense ⁶⁸Ga-FAPI-04 uptake with continuous wash-out in the infarct territory of coronary occlusion correlating with T1 and ECV mapping was observed. The uptake of ⁶⁸Ga-FAPI-04 extends beyond the actual infarcted area and overestimates the infarct size as confirmed by follow-up CMR.

Technical advances in radiotherapy (RT) treatment planning and delivery have substantially changed RT concepts for primary prostate cancer (PCa) by (i) enabling a reduction of treatment time, and by (ii) enabling safe delivery of high RT doses. Several studies proposed a dose–response relationship for patients with primary PCa and especially in patients with high-risk features, as dose escalation leads to improved tumor control. In parallel to the improvements in RT techniques, diagnostic imaging techniques like multiparametric magnetic resonance imaging (mpMRI) and positron-emission tomography targeting prostate-specific-membrane antigen (PSMA-PET) evolved and enable an accurate depiction of the intraprostatic tumor mass for the first time. The HypoFocal-SBRT study combines ultra-hypofractionated RT/stereotactic body RT, with focal RT dose escalation on intraprostatic tumor sides by applying state of the art diagnostic imaging and most modern RT concepts. This novel strategy will be compared with moderate hypofractionated RT (MHRT), one option for the curative primary treatment of PCa, which has been proven by several prospective trials and is recommended and carried out worldwide. We suspect an increase in relapse-free survival (RFS), and we will assess quality of life in order to detect potential changes.

The central paradigm of novel therapeutic approaches in cancer therapy is identifying and targeting molecular biomarkers. One such target is the nuclear DNA repair enzyme Poly-(ADP ribose) polymerase 1 (PARP1). Sensitivity to PARP inhibition in certain cancers such as gBRCA^mut breast and ovarian cancers has led to its exploitation as a target. The overexpression of PARP1 in several types of cancer further evoked interest in its use as an imaging target. While PARP1-targeted inhibitors have fast developed and approved in this past decade, determination of PARP1 expression might help to predict the response to PARP inhibitor treatment. This has the potential of improving prognosis and moving towards tailored therapy options and/or dosages. This review summarizes the recent pre-clinical advancements in imaging and theranostic PARP1 targeted tracers. To assess PARP1 levels, several imaging probes with fluorescent or beta/gamma emitting radionuclides have been proposed and three have advanced to ongoing clinical evaluation. Apart from its diagnostic value in detection of primary tumors as well as metastases, this shall also help in delivering therapeutic radionuclides to PARP1 overexpressing tumors. Henceforth nuclear medicine has now advanced towards conjugating theranostic radionuclides to PARP1 inhibitors. This paves the way for a future of PARP1-targeted theranostics and personalized therapy.