Apoptosis Imaging in Oncology by Means of Positron Emission Tomography: A Review.

To date, a wide variety of potential PET-apoptosis imaging radiopharmaceuticals targeting apoptosis-induced cell membrane asymmetry and acidification, as well as caspase 3 activation (substrates and inhibitors) have been developed with the purpose of rapidly assessing the response to treatment in cancer patients. Many of these probes were shown to specifically bind to their apoptotic target in vitro and their uptake to be enhanced in the in vivo-xenografted tumours in mice treated by means of chemotherapy, however, to a significantly variable degree. This may, in part, relate to the tumour model used given the fact that different tumour cell lines bear a different sensitivity to a similar chemotherapeutic agent, to differences in the chemotherapeutic concentration and exposure time, as well as to the different timing of imaging performed post-treatment. The best validated cell membrane acidification and caspase 3 targeting radioligands, respectively 18F-ML-10 from the Aposense family and the radiolabelled caspase 3 substrate 18F-CP18, have also been injected in healthy individuals and shown to bear favourable dosimetric and safety characteristics. However, in contrast to, for instance, the 99mTc-HYNIC-Annexin V, neither of both tracers was taken up to a significant degree by the bone marrow in the healthy individuals under study. Removal of white and red blood cells from the bone marrow through apoptosis plays a major role in the maintenance of hematopoietic cell homeostasis. The major apoptotic population in normal bone marrow are immature erythroblasts. While an accurate estimate of the number of immature erythroblasts undergoing apoptosis is not feasible due to their unknown clearance rate, their number is likely substantial given the ineffective quote of the erythropoietic process described in healthy subjects. Thus, the clinical value of both 18F-ML-10 and 18F-CP18 for apoptosis imaging in cancer patients, as suggested by a small number of subsequent clinical phase I/II trials in patients suffering from primary or secondary brain malignancies using 18F-ML-10 and in an ongoing trial in patients suffering from cancer of the ovaries using 18F-CP18, remains to be proven and warrants further investigation.

PSMA expression on neovasculature of solid tumors.

The use of prostate specific membrane antigen (PSMA) binding agents, labelled with diagnostic and therapeutic radio-isotopes is opening the potential for a new era of personalized management of prostate carcinoma. A wide variety of immunohistochemistry studies have shown PSMA also to be upregulated on the endothelial cells of the neovasculature of a wide variety of other solid tumors where it may facilitate endothelial cell sprouting and invasion through its regulation of lytic proteases that have the ability to cleave the extracellular matrix. Similar to the introduction of PSMA-targeting theranostics in prostate carcinoma, overexpression of PSMA on newly formed tumor vessels may serve as a target for imaging and subsequent treatment of cancer through the use of agents that are capable of blocking PSMA in its function or through PSMA-mediated delivery of chemotherapeutics or radiation agents. In this review, the available data on PSMA expression on tumor neovasculature in human solid tumors assessed by using immunohistochemistry are discussed.

PSMA-Targeting Positron Emission Agents for Imaging Solid Tumors Other Than Non-Prostate Carcinoma: A Systematic Review.

Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a wide variety of solid tumors other than prostate carcinoma. Accordingly, positron-emitting radiolabeled small molecules targeting PSMA, initially developed for positron emission tomography in prostate carcinomas, are currently being explored for their staging and restaging potential as an alternative imaging modality in other solid tumor types where 18-F-fluorodeoxyglucose (FDG)-PET imaging has low diagnostic accuracy. In this paper, the currently available literature in this field is reviewed. Preliminary, mainly retrospective studies are encouraging, with evidence of improved diagnostic sensitivity and specificity in clear cell renal carcinoma, glioma, and hepatocellular carcinoma, leading to a change in patient management in several patients. However, the results published thus far warrant confirmation by larger prospective studies additionally assessing the longitudinal impact on patient outcomes.

An observational pilot study to evaluate the feasibility and quality of oncological home-hospitalization.

PURPOSE: The objective of this pilot study was to evaluate the feasibility of oncological home-hospitalization and to compare its quality with standard ambulatory hospital care in terms of patient-reported quality of life and related endpoints by means of a set of validated patient-reported outcome measures (PROMs). METHODS: An observational cohort study (clinicaltrials.gov identifier: NCT03073499) was conducted, allocating patients to (partial) home-hospitalization or standard ambulatory hospital care. PROMs were completed by both cohorts at start of treatment and eight weeks later. An additional study-specific questionnaire was presented to the intervention cohort at study-end assessing their satisfaction with and preferences for the provided homecare. RESULTS: Thirty patients received home-hospitalization, corresponding to 116 interventions. For twenty-eight patients, this comprised all assessments required prior to administration of treatment, which resulted in a significant reduction of waiting time for treatment administration at the hospital in comparison with the control cohort (n = 24) (average reduction of 1:12 h, p < 0.001). Two patients received actual subcutaneous therapy at home. None of the PROM's evaluated revealed significant differences between both cohorts (all p > 0.05). 29/30 patients of the intervention cohort were satisfied with the provided homecare and preferred to have it continued, 22/25 patients declared to feel at home at least as safe as in the hospital. No serious safety concerns were reported. CONCLUSION: The results of this pilot study suggest that (partial) oncological home-hospitalization is feasible, safe and statistically not affecting patient-reported quality of life. Furthermore, this care model was acceptable and preferred by a substantial number of cancer patients.

Organization, quality and cost of oncological home-hospitalization: A systematic review.

BACKGROUND: Home-hospitalization might be a patient-centred approach facing the increasing burden of cancer on societies. This systematic review assessed how oncological home-hospitalization has been organized and to what extent its quality and costs were evaluated. RESULTS: Twenty-four papers describing parenteral cancer drug administration to adult patients in their homes were included. Most papers concluded oncological home-hospitalization had no significant effect on patient-reported quality of life (7/8 = 88%), but large majority of patients were satisfied (12/13, 92%) and preferred home treatment (7/8, 88%). No safety risks were associated with home-hospitalization (10/10, 100%). The cost of home-hospitalization was found beneficial in five trials (5/9, 56%); others reported no financial impact (2/9, 22%) or additional costs (2/9, 22%). CONCLUSION: Despite heterogeneity, majority of reported models for oncological home-hospitalization demonstrated that this is a safe, equivalent and acceptable alternative to ambulatory hospital care. More well-designed trials are needed to evaluate its economic impact.