Simple Summary Monoclonal antibodies (mAbs) have the ability to specifically target tumor-cell antigens. This unique property has led to their use in the delivery of radioisotopes to tumor sites (scintigraphic imaging and radioimmunotherapy (RIT)). The choice of the radionuclide depends on its unique physical properties and intended use. Using radiolabeled mAbs with imaging techniques provides critical data that are essential for predicting side effects and determining an optimal antibody dose and treatment schedule. While RIT has been successful in the management of hematological malignancies, the treatment of solid tumors remains challenging. Various strategies are being investigated to improve the efficacy of RIT in solid tumors. Abstract Radioimmunoconjugates consist of a monoclonal antibody (mAb) linked to a radionuclide. Radioimmunoconjugates as theranostics tools have been in development with success, particularly in hematological malignancies, leading to approval by the US Food and Drug Administration (FDA) for the treatment of non-Hodgkin’s lymphoma. Radioimmunotherapy (RIT) allows for reduced toxicity compared to conventional radiation therapy and enhances the efficacy of mAbs. In addition, using radiolabeled mAbs with imaging methods provides critical information on the pharmacokinetics and pharmacodynamics of therapeutic agents with direct relevance to the optimization of the dose and dosing schedule, real-time antigen quantitation, antigen heterogeneity, and dynamic antigen changes. All of these parameters are critical in predicting treatment responses and identifying patients who are most likely to benefit from treatment. Historically, RITs have been less effective in solid tumors; however, several strategies are being investigated to improve their therapeutic index, including targeting patients with minimal disease burden; using pre-targeting strategies, newer radionuclides, and improved labeling techniques; and using combined modalities and locoregional application. This review provides an overview of the radiolabeled intact antibodies currently in clinical use and those in development.

/pdf/radiolabeled-antibodies-for-cancer-imaging-and-therapy-1ykdrmz1.pdf

Radiolabeled Antibodies for Cancer Imaging and Therapy

Cardiac 123I-mIBG scintigraphy for prediction of catheter ablation outcome in patients with atrial fibrillation.

Zirconium immune-complexes for PET molecular imaging: Current status and prospects

Abstract Purpose Heart failure (HF) is a primary cause of morbidity and mortality worldwide, with significant impact on life quality and extensive healthcare costs. Assessment of myocardial sympathetic innervation function plays a central role in prognosis assessment in HF patients. The aim of this review is to summarize the most recent evidence regarding the clinical applications of iodine-123 metaiodobenzylguanidine ( 123 I-MIBG) imaging in patients with HF and related comorbidities. Methods A comprehensive literature search was conducted on PubMed and Web of Science databases. Articles describing the impact of 123 I-MIBG imaging on HF and related comorbidities were considered eligible for the review. Results We collected several data reporting that 123 I-MIBG imaging is a safe and non-invasive tool to evaluate dysfunction of cardiac sympathetic neuronal function and to assess risk stratification in HF patients. HF is frequently associated with comorbidities that may affect cardiac adrenergic innervation. Furthermore, HF is frequently associated with comorbidities and chronic conditions, such as diabetes, obesity, kidney disease and others, that may affect cardiac adrenergic innervation. Conclusion Comorbidities and chronic conditions lead to more severe impairment of sympathetic nervous system in patients with HF, with a negative impact on disease progression and outcome. Cardiac imaging with 123 I-MIBG can be a useful tool to reduce morbidity and prevent adverse events in HF patients. 

/pdf/123i-mibg-imaging-in-heart-failure-impact-of-comorbidities-20io5tqz.pdf

123I-MIBG imaging in heart failure: impact of comorbidities on cardiac sympathetic innervation

Introduction Mesothelin (MSLN) is overexpressed in a wide variety of cancers with few therapeutic options and has recently emerged as an attractive target for cancer therapy, with a large number of approaches currently under preclinical and clinical investigation. In this respect, developing mesothelin specific tracers as molecular companion tools for predicting patient eligibility, monitoring then response to mesothelin-targeting therapies, and tracking the evolution of the disease or for real-time visualisation of tumours during surgery is of growing importance. Methods We generated by phage display a nanobody (Nb S1) and used enzymatic approaches were used to site-directed conjugate Nb S1 with either ATTO 647N fluorochrome or NODAGA chelator for fluorescence and positron emission tomography imaging (PET) respectively. Results We demonstrated that Nb S1 displays a high apparent affinity and specificity for human mesothelin and demonstrated that the binding, although located in the membrane distal domain of mesothelin, is not impeded by the presence of MUC16, the only known ligand of mesothelin, nor by the therapeutic antibody amatuximab. In vivo experiments showed that both ATTO 647N and [68Ga]Ga-NODAGA-S1 rapidly and specifically accumulated in mesothelin positive tumours compared to mesothelin negative tumours or irrelevant Nb with a high tumour/background ratio. The ex vivo biodistribution profile analysis also confirmed a significantly higher uptake of Nb S1 in MSLN-positive tumours than in MSLNlow tumours. Conclusion We demonstrated for the first time the use of an anti-MSLN nanobody as PET radiotracer for same day imaging of MSLN+ tumours, targeting an epitope compatible with the monitoring of amatuximab-based therapies and current SS1-derived-drug conjugates.

/pdf/rapid-nanobody-based-imaging-of-mesothelin-expressing-1zf421ck.pdf

Rapid nanobody-based imaging of mesothelin expressing malignancies compatible with blocking therapeutic antibodies

The aim of this review is to summarize the main applications of mesothelin-targeting agents in the diagnosis of different types of cancers with a brief mention of nuclear magnetic resonance. The articles taken into account were selected from PubMed, Scopus, and Web of Sciences, including research articles and abstracts that deal with radioimmunotherapy and new tracers for nuclear medicine and radiodiagnosis. Articles that are not in English have been excluded. Mesothelin-targeting agents were the subject of the selected articles in which tracers as 64Cu-DOTA-11-25mAb anti MSLN, 111In-MORAb-009-CHX-A″, 89Zr-MMOT0530A, 111In-amatuximab, 99mTc-A1, 89Zr-AMA, 89Zr-amatuximab, 64Cu-amatuximab, 89Zr-labeled MMOT0530A and 89Zr-B3 found application in detection of malignancies that overexpressed mesothelin. Only one article approached magnetic resonance imaging (MRI) diagnosis using superparamagnetic iron oxide nanoparticles linked to anti-mesothelin antibodies. The tracers proved to be highly sensitive in detecting mesothelin positive cells. 89Zr-labeled MMOT0530A could also be used to predict the suitability of patients to radioimmunotherapy. Radiolabeled anti-mesothelin antibodies could be crucial as a treatment tool and for predicting the eligibility and the response of the patient to radioimmunotherapy through the study of the expression grade of mesothelin. They can be a relevant tool for pancreatic adenocarcinoma, lung cancer, human epidermoid carcinoma, ovarian cancer, malignant mesothelioma in which mesothelin is widely expressed.

/pdf/new-insight-and-future-perspective-of-mesothelin-targeted-327xa6rln7.pdf

New insight and future perspective of mesothelin-targeted agents in nuclear medicine

BACKGROUND
Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy.


OBJECTIVE
The aim of this study was to associate BSI with OS in bone metastatic BC patients.


METHODS
In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account.


RESULTS
Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924).


CONCLUSION
Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population.

Evaluation of bone scan index as a prognostic tool in breast cancer patients with bone metastasis.

https://link.springer.com/content/pdf/10.1007/s12350-020-02501-w.pdf

The prognostic value of 123I-mIBG SPECT cardiac imaging in heart failure patients: a systematic review

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New insight and future perspective of mesothelin-targeted agents in nuclear medicine

Evaluation of bone scan index as a prognostic tool in breast cancer patients with bone metastasis.

The prognostic value of 123I-mIBG SPECT cardiac imaging in heart failure patients: a systematic review