The targeted delivery of radionuclides to tumours holds great promise for diagnosis and treatment of malignant neoplasms. The development of scaffold proteins has significantly simplified the design of targeting agents with desirable properties. This review comprehensively describes the key aspects of the design of radionuclide compounds, including classification of radionuclides, methodology for their attachment to targeting agents and characteristics of these agents that affect their behaviour in the body. Various targeting molecules are compared in terms of their ability to specifically find malignant foci in the body. The most recent achievements of cancer theranostics that aim at increasing the selectivity of antitumour effect are described, such as the fusion of targeting scaffold proteins with the albumin-binding domain and pretargeting. Special attention is paid to the creation of targeted radionanomaterials. Advantages and disadvantages of different strategies are analyzed and approaches for improving the delivery to tumours and for minimizing the undesirable impact on healthy organs and tissues are proposed. Particular emphasis is placed on the results of studies published in 2020–2021 that have not yet been covered by reviews. The bibliography includes 191 references.
1 January 2006 in European Journal of Cardio-Thoracic Surgery
The aim of this study was to evaluate cognitive function, as measured by serial neuropsychological testing, and cerebral perfusion, as measured by brain SPECT scanning in patients with coronary artery diseases (CAD) following off-pump and on-pump coronary artery bypass graft surgery. Besides, the relationship between cerebral blood flow, cognitive functions, surgery parameters, and cardiac function in these patients were estimated. Also, brain-protective effects of instenon were studied. Brain SPECT and comprehensive neuropsychological testing were performed 1 day before, 10-14 days and 6 months after coronary artery bypass graft surgery (CABG). The study involved 65 patients (62 males and 3 females, mean age 55+/-2) who underwent CABG with cardiopulmonary bypass (CPB) (43 pts) and off-pump coronary revascularization (OPCAB) using the Octopus stabilization system (22 pts). In 21 cases employing CPB, for prevention of the impairments of cerebral perfusion and cognitive deficit instenon was administered. CABG with the use of extracorporeal circulation is complicated by short-term and long-term neurocognitive dysfunction (in 96 and 55% cases, correspondingly). Also, in the early period after CABG, in 68% patients, decrease in regional cerebral blood flow (rCBF) was found, and after 6 months brain perfusion was lower than the baseline in 55% cases. Relationship between postoperative rCBF changes and the dynamics of cognitive function was found in early period and after 6 months following CABG. The coronary revascularization on beating heart or preventive administration of instenon in CPB patients helps significantly to diminish the risk of cerebrovascular complication.
The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [99mTc]Tc-maSSS-PEG2-RM26 in PCa and BCa patients. Planar and whole-body SPECT/CT imaging was performed in six PCa patients and seven BCa patients 2, 4, 6, and 24 h post the intravenous administration of 40 µg of [99mTc]Tc-maSSS-PEG2-RM26 (600–700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [99mTc]Tc-maSSS-PEG2-RM26 was observed with predominantly hepatobiliary excretion. The effective doses were 0.0053 ± 0.0007 for male patients and 0.008 ± 0.003 mSv/MBq for female patients. The accumulation of [99mTc]Tc-maSSS-PEG2-RM26 in tumors was observed in four out of six PCa and in seven out of seven BCa patients. In four BCa patients, a high uptake of the agent into the axillary lymph nodes was detected. Immunohistochemistry revealed positive GRPR expression in 60% of primary PCa, 71.4% of BCa tumors, and 50% of examined BCa lymph nodes. In conclusion, a single administration of [99mTc]Tc-maSSS-PEG2-RM26 was safe and well tolerated. [99mTc]Tc-maSSS-PEG2-RM26 SPECT may be useful for tumor detection in PCa and BCa patients, pending further studies.
Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [99mTc]Tc-ZHER2:V2 and [99mTc]Tc-ZHER2:2395. [99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99mTc using a GGGC chelator. The new probe, [99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.
Objectives: The aim of this cohort study is to improve the procedure of fertility-sparing surgery and to assess oncological and reproductive follow-up outcomes after radical trachelectomy (RT) for cervical cancer (T1a2-1bNxM0). Methods: We have suggested the method combining sentinel lymph nodes (SLNs) and cervicoisthmic cerclage using a superelastic knitted TiNi mesh (KTNM) implant to facilitate the primary biomechanical/retention function of the uterus. Sixty-eight consented patients, who underwent fertility-sparing surgery using both transabdominal and laparoscopic route from 2009 through 2019, were recruited in the study and prospectively followed for a mean of 69 months. Results: There were no intraoperative or postoperative complications. No cervical stenoses or mesh failures were noted in all cases. The 5‐year overall and recurrence‐free survival rates were 100% and 97%, respectively. Two patients indicated recurrence, it occurred in 3 and 36 months. There were 19 (28%) spontaneous pregnancies, 6 resulted in full-term delivery, whereas 2 and 11 ended in miscarriage and early abortion, respectively. Conclusions: This sparing-surgery technique is turned out to be feasible and efficient as allows to achieve well oncologic and fertility outcomes, mimicking the effect of the cervix. It complements existing surgical approaches and may provide further insight into how to overcome challenges even in aggravated cases or previously failed procedures.