On Earth, humans are subjected to a gravitational force that has been an important determinant in human evolution and function. During spaceflight, astronauts are subjected to several hazards including a prolonged state of microgravity that induces a myriad of physiological adaptations leading to orthostatic intolerance. This review summarises all known cardiovascular diseases related to human spaceflight and focusses on the cardiovascular changes related to human spaceflight (in vivo) as well as cellular and molecular changes (in vitro). Upon entering microgravity, cephalad fluid shift occurs and increases the stroke volume (35–46%) and cardiac output (18–41%). Despite this increase, astronauts enter a state of hypovolemia (10–15% decrease in blood volume). The absence of orthostatic pressure and a decrease in arterial pressures reduces the workload of the heart and is believed to be the underlying mechanism for the development of cardiac atrophy in space. Cellular and molecular changes include altered cell shape and endothelial dysfunction through suppressed cellular proliferation as well as increased cell apoptosis and oxidative stress. Human spaceflight is associated with several cardiovascular risk factors. Through the use of microgravity platforms, multiple physiological changes can be studied and stimulate the development of appropriate tools and countermeasures for future human spaceflight missions in low Earth orbit and beyond.

At present, prostate cancer remains the second most occurring cancer in men, in Europe. Treatment efficacy for therapy of advanced metastatic disease, and metastatic castration-resistant prostate cancer in particular is limited. Prostate-specific membrane antigen (PSMA) is a promising therapeutic target in prostate cancer, seeing the high amount of overexpression on prostate cancer cells. Clinical investigation of PSMA-targeted radionuclide therapy has shown good clinical efficacy. However, adverse effects are observed of which salivary gland hypofunction and xerostomia are among the most prominent. Salivary gland toxicity is currently the dose-limiting side effect for PSMA-targeted radionuclide therapy, and more specifically for PSMA-targeted alpha therapy. To date, mechanisms underlying the salivary gland uptake of PSMA-targeting compounds and the subsequent damage to the salivary glands remain largely unknown. Furthermore, preventive strategies for salivary gland uptake or strategies for treatment of salivary gland toxicity are needed. This review focuses on the current knowledge on uptake mechanisms of PSMA-targeting compounds in the salivary glands and the research performed to investigate different strategies to prevent or treat salivary gland toxicity.

Human spaceflight is entering a new era of sustainable human space exploration. By 2030 humans will regularly fly to the Moon’s orbit, return to the Moon’s surface and preparations for crewed Mars missions will intensify. In planning these undertakings, several challenges will need to be addressed in order to ensure the safety of astronauts during their space travels. One of the important challenges to overcome, that could be a major showstopper of the space endeavor, is the exposure to the space radiation environment. There is an urgent need for quantifying, managing and limiting the detrimental health risks and electronics damage induced by space radiation exposure. Such risks raise key priority topics for space research programs. Risk limitation involves obtaining a better understanding of space weather phenomena and the complex radiation environment in spaceflight, as well as developing and applying accurate dosimetric instruments, understanding related short- and long-term health risks, and strategies for effective countermeasures to minimize both exposure to space radiation and the remaining effects post exposure. The ESA/SciSpacE Space Radiation White Paper identifies those topics and underlines priorities for future research and development, to enable safe human and robotic exploration of space beyond Low Earth Orbit.

Peptide receptor radionuclide therapy (PRRT) is used for the treatment of patients with unresectable or metastasized somatostatin receptor type 2 (SSTR2)-expressing gastroenteropancreatic neuroendocrine tumours (GEP-NETs). The radiolabelled somatostatin analogue [177Lu]Lu-DOTA-TATE delivers its radiation dose to SSTR2-overexpressing tumour cells, resulting in selective cell killing during radioactive decay. While tumour control can be achieved in many patients, complete remissions remain rare, causing the majority of patients to relapse after a certain period of time. This raises the question whether the currently fixed treatment regime (4 × 7.4 GBq) leaves room for dose escalation as a means of improving therapy efficacy. The kidneys have shown to play an important role in defining a patient's tolerability to PRRT. As a consequence of the proximal tubular reabsorption of [177Lu]Lu-DOTA-TATE, via the endocytic megalin/cubilin receptor complex, the radionuclides are retained in the renal interstitium. This results in extended retention of radioactivity in the kidneys, generating a risk for the development of radiation nephropathy. In addition, a decreased kidney function has shown to be associated with a prolonged circulation of [177Lu]Lu-DOTA-TATE, causing increased irradiation to the bone marrow. This can on its turn lead to myelosuppression and haematological toxicity, owing to the marked radio sensitivity of the rapidly proliferating cells in the bone marrow. In contrast to external beam radiotherapy (EBRT), the exact absorbed dose limits for these critical organs (kidneys and bone marrow) in PRRT with [177Lu]Lu-DOTA-TATE are still unclear. Better insights into these uncertainties, can help in optimizing PRRT to reach its maximum therapeutic potential, while avoiding severe adverse events, like nephropathy and hematologic toxicities. In this review we focus on the nephrotoxic effects of PRRT with [177Lu]Lu-DOTA-TATE for the treatment of GEP-NETs. If the absorbed dose to the kidneys can be lowered, higher activities can be administered, enlarging the therapeutic window for PRRT. Therefore, we evaluated the renal protective potential of current and promising future strategies and discuss the importance of (renal) dosimetry in PRRT.

Biofabrication in space is one of the novel promising and prospective research directions in the rapidly emerging field of space STEM. There are several advantages of biofabrication in space. Under microgravity, it is possible to engineer constructs using more fluidic channels and thus more biocompatible bioinks. Microgravity enables biofabrication of tissue and organ constructs of more complex geometries, thus facilitating novel scaffold-, label-, and nozzle-free technologies based on multi-levitation principles. However, when exposed to microgravity and cosmic radiation, biofabricated tissues could be used to study pathophysiological phenomena that will be useful on Earth and for deep space manned missions. Here, we provide leading concepts about the potential mutual benefits of the application of biofabrication technologies in space.

Ionizing radiation and microgravity are two considerable health risks encountered during deep space exploration. Both have deleterious effects on the human body. On one hand, weightlessness is known to induce a weakening of the immune system, delayed wound healing and musculoskeletal, cardiovascular, and sensorimotor deconditioning. On the other hand, radiation exposure can lead to long-term health effects such as cancer and cataracts as well as have an adverse effect on the central nervous and cardiovascular systems. Ionizing radiation originates from three main sources in space: galactic cosmic radiation, solar particle events and solar winds. Furthermore, inside the spacecraft and inside certain space habitats on Lunar and Martian surfaces, the crew is exposed to intravehicular radiation, which arises from nuclear reactions between space radiation and matter. Besides the approaches already in use, such as radiation shielding materials (such as aluminium, water or polyethylene), alternative shielding materials (including boron nanotubes, complex hybrids, composite hybrid materials, and regolith) and active shielding (using fields to deflect radiation particles) are being investigated for their abilities to mitigate the effects of ionizing radiation. From a biological point of view, it can be predicted that exposure to ionizing radiation during missions beyond Low Earth Orbit (LEO) will affect the human body in undesirable ways, e.g., increasing the risks of cataracts, cardiovascular and central nervous system diseases, carcinogenesis, as well as accelerated ageing. Therefore, it is necessary to assess the risks related to deep space exploration and to develop mitigation strategies to reduce these risks to a tolerable level. By using biomarkers for radiation sensitivity, space agencies are developing extensive personalised medical examination programmes to determine an astronaut's vulnerability to radiation. Moreover, researchers are developing pharmacological solutions (e.g., radioprotectors and radiomitigators) to proactively or reactively protect astronauts during deep space exploration. Finally, research is necessary to develop more effective countermeasures for use in future human space missions, which can also lead to improvements to medical care on Earth. This review will discuss the risks space travel beyond LEO poses to astronauts, methods to monitor astronauts' health, and possible approaches to mitigate these risks.