Combination of sunitinib and Lu-labeled antibody cG250 targeted radioimmunotherapy: A promising new therapeutic strategy for patients with advanced renal cell cancer.

Sunitinib is an effective treatment for patients with metastatic Renal Cell Carcinoma (mRCC) but ultimately resistance occurs. The aim of this study was to investigate sunitinib resistance in RCCs and to develop therapeutic combination strategies with targeted radioimmunotherapy (RIT). We studied two RCC models, analyzed Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) and AXL/MET expression and performed therapy studies in Balb/c mice combining sunitinib and [Lu]Lu-cG250 RIT (6.

Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin.

In patients with colorectal peritoneal metastases scheduled for cytoreductive surgery, accurate preoperative estimation of tumor burden and subsequent intraoperative detection of all tumor deposits remains challenging. In this study (ClinicalTrials.gov NCT03699332) we describe the results of a phase I clinical trial evaluating [In]In-DOTA-labetuzumab-IRDye800CW, a dual-labeled anti-carcinoembryonic antigen (anti-CEA) antibody conjugate that enables both preoperative imaging and intraoperative radioguidance and fluorescence imaging.

Novel VHH-Based Tracers with Variable Plasma Half-Lives for Imaging of CAIX-Expressing Hypoxic Tumor Cells.

Hypoxic areas are present in the majority of solid tumors, and hypoxia is associated with resistance to therapies and poor outcomes. A transmembrane protein that is upregulated by tumor cells that have adapted to hypoxic conditions is carbonic anhydrase IX (CAIX). Therefore, noninvasive imaging of CAIX could be of prognostic value, and it could steer treatment strategies.

Imaging carbonic anhydrase IX as a method for monitoring hypoxia-related radioresistance in preclinical head and neck cancer models.

Background And Purpose: Tumor hypoxia is an important cause of radioresistance and is associated with poor outcome.SPECT (Single-photon emission computed tomography) imaging enables visualizing tumor characteristics. We investigated the SPECT-radiotracer [In]-girentuximab-F(ab') to image Carbonic Anhydrase IX (CAIX), an enzyme upregulated under hypoxic conditions.

Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy.

Simlukafusp alfa (FAP-IL2v, RO6874281/RG7461) is an immunocytokine comprising an antibody against fibroblast activation protein α (FAP) and an IL-2 variant with a retained affinity for IL-2Rβγ > IL-2 Rβγ and abolished binding to IL-2 Rα. Here, we investigated the immunostimulatory properties of FAP-IL2v and its combination with programmed cell death protein 1 (PD-1) checkpoint inhibition, CD40 agonism, T cell bispecific and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. The binding and immunostimulatory properties of FAP-IL2v were investigated and compared with FAP-IL2wt.

Pyruvate-lactate exchange and glucose uptake in human prostate cancer cell models. A study in xenografts and suspensions by hyperpolarized [1- C]pyruvate MRS and [ F]FDG-PET.

Reprogramming of energy metabolism in the development of prostate cancer can be exploited for a better diagnosis and treatment of the disease. The goal of this study was to determine whether differences in glucose and pyruvate metabolism of human prostate cancer cells with dissimilar aggressivenesses can be detected using hyperpolarized [1- C]pyruvate MRS and [ F]FDG-PET imaging, and to evaluate whether these measures correlate. For this purpose, we compared murine xenografts of human prostate cancer LNCaP cells with those of more aggressive PC3 cells.

Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity.

Platinum-based chemotherapeutics exhibit excellent antitumor properties. However, these drugs cause severe side effects including toxicity, drug resistance, and lack of tumor selectivity. Tumor-targeted drug delivery has demonstrated great potential to overcome these drawbacks.

[Tc]-labelled interleukin-8 as a diagnostic tool compared to [F]FDG and CT in an experimental porcine osteomyelitis model.

Osteomyelitis (OM) is an important cause of morbidity and sometimes mortality in children and adults. Long-term complications can be reduced when treatment is initiated in an early phase. The diagnostic gold standard is microbial examination of a biopsy and current non-invasive imaging methods are not always optimal.

Carcinoembryonic antigen-targeted photodynamic therapy in colorectal cancer models.

Background: In colorectal cancer, survival of patients is drastically reduced when complete resection is hampered by involvement of critical structures. Targeted photodynamic therapy (tPDT) is a local and targeted therapy which could play a role in eradicating residual tumor cells after incomplete resection. Since carcinoembryonic antigen (CEA; CEACAM5) is abundantly overexpressed in colorectal cancer, it is a potential target for tPDT of colorectal cancer.

CAIX-targeting radiotracers for hypoxia imaging in head and neck cancer models.

Hypoxia-induced carbonic anhydrase IX (CAIX) expression is a prognostic marker in solid tumors. In recent years many radiotracers have been developed, but a fair comparison of these compounds is not possible because of the diversity in tumor models and other experimental parameters. In this study we performed a direct in vivo comparison of three promising CAIX targeting radiotracers in xenografted head and neck cancer models.

Follow-up imaging after cryoablation of clear cell renal cell carcinoma is feasible using single photon emission computed tomography with In-girentuximab.

Purpose: Detection of residual or recurrent vital renal tumor on follow-up (FU) cross-sectional imaging after ablative therapy is challenging. The specific and high expression levels of carbonic anhydrase IX (CAIX) in clear cell renal cell carcinoma (ccRCC) makes it a suitable target for imaging using radiolabeled anti-CAIX antibody girentuximab. The objective of this study was to evaluate the feasibility of targeted FU imaging 1 month after cryoablation of ccRCC using single photon emission computed tomography (SPECT) after In-labeled girentuximab administration.

PSMA-targeting agents for radio- and fluorescence-guided prostate cancer surgery.

Despite recent improvements in imaging and therapy, prostate cancer (PCa) still causes substantial morbidity and mortality. In surgical treatment, incomplete resection of PCa and understaging of possible undetected metastases may lead to disease recurrence and consequently poor patient outcome. To increase the chance of accurate staging and subsequently complete removal of all cancerous tissue, prostate specific membrane antigen (PSMA) targeting agents may provide the surgeon an aid for the intraoperative detection and resection of PCa lesions.

A Clinical Feasibility Study to Image Angiogenesis in Patients with Arteriovenous Malformations Using Ga-RGD PET/CT.

Arteriovenous malformations (AVMs) have an inherent capacity to form new blood vessels, resulting in excessive lesion growth, and this process is further triggered by the release of angiogenic factors. Ga-labeled arginine-glycine-aspartate tripeptide sequence (RGD) PET/CT imaging may provide insight into the angiogenic status and treatment response of AVMs. This clinical feasibility study was performed to demonstrate that Ga-RGD PET/CT imaging can be used to quantitatively assess angiogenesis in peripheral AVMs.

A pretargeted multimodal approach for image-guided resection in a xenograft model of colorectal cancer.

Background: Image-guided surgery may improve surgical outcome for colorectal cancer patients. Here, we evaluated the feasibility of a pretargeting strategy for multimodal imaging in colorectal cancer using an anti-carcinoembryonic antigen (CEA) x anti-histamine-succinyl-glycine (HSG) bispecific antibody (TF2) in conjunction with the dual-labeled diHSG peptide (RDC018), using both a fluorophore for near-infrared fluorescence imaging and a chelator for radiolabeling.

Methods: Nude mice with subcutaneous (s.

Development and characterization of a theranostic multimodal anti-PSMA targeting agent for imaging, surgical guidance, and targeted photodynamic therapy of PSMA-expressing tumors.

Prostate cancer (PCa) recurrences after surgery frequently occur. To improve the outcome after surgical resection of the tumor, the theranostic multimodal anti-PSMA targeting agent In-DTPA-D2B-IRDye700DX was developed and characterized for both pre- and intra-operative tumor localization and eradication of (residual) tumor tissue by PSMA-targeted photodynamic therapy (tPDT), which is a highly selective cancer treatment based on targeting molecules conjugated to photosensitizers that can induce cell destruction upon exposure to near-infrared (NIR) light. The anti-PSMA monoclonal antibody D2B was conjugated with IRDye700DX and DTPA and subsequently radiolabeled with In.

Lesion detection by [Zr]Zr-DFO-girentuximab and [F]FDG-PET/CT in patients with newly diagnosed metastatic renal cell carcinoma.

Purpose: The main objective of this preliminary analysis of the IMaging PAtients for Cancer drug selecTion (IMPACT)-renal cell cancer (RCC) study is to evaluate the lesion detection of baseline contrast-enhanced CT, [Zr]Zr-DFO-girentuximab-PET/CT and [F]FDG-PET/CT in detecting ccRCC lesions in patients with a good or intermediate prognosis metastatic clear cell renal cell carcinoma (mccRCC) according to the International Metastatic Database Consortium (IMDC) risk model.

Methods: Between February 2015 and March 2018, 42 newly diagnosed mccRCC patients with good or intermediate prognosis, eligible for watchful waiting, were included. Patients underwent CT, [Zr]Zr-DFO-girentuximab-PET/CT and [F]FDG-PET/CT at baseline.

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for Zr-immunoPET.

Purpose: Currently, the most commonly used chelator for labelling antibodies with Zr for immunoPET is desferrioxamine B (DFO). However, preclinical studies have shown that the limited in vivo stability of the Zr-DFO complex results in release of Zr, which accumulates in mineral bone. Here we report a novel chelator DFOcyclo*, a preorganized extended DFO derivative that enables octacoordination of the Zr radiometal.

Monitoring In-labelled polyisocyanopeptide (PIC) hydrogel wound dressings in full-thickness wounds.

Wounds often result in scarring, prolonged morbidity, and loss of function. New interactive and modifiable hydrogel wound dressings are being developed for these injuries. Polyisocyanopeptide (PIC) gel is a promising thermosensitive hydrogel having several characteristics that can facilitate wound repair, including ease of application/removal and strain-stiffening properties that mimic extracellular matrix components.

In Vitro and In Vivo Characterization of an F-AlF-Labeled PSMA Ligand for Imaging of PSMA-Expressing Xenografts.

The aim was to compare the prostate-specific membrane antigen (PSMA)-targeting characteristics of PSMA-11, radiolabeled on the basis of chelation of F-AlF, with those of Ga-PSMA-11 to image PSMA-expressing xenografts. Labeling of F-AlF-PSMA-11 via F-AlF-complexation was performed as described by Boschi et al. and Malik et al.

Quantitative Imaging of the Hypoxia-Related Marker CAIX in Head and Neck Squamous Cell Carcinoma Xenograft Models.

Tumor hypoxia plays a major role in radio- and chemotherapy resistance in solid tumors. Carbonic Anhydrase IX (CAIX) is an endogenous hypoxia-related protein, which is associated with poor patient outcome. The quantitative assessment of CAIX expression of tumors may steer cancer treatment by predicting therapy response or patient selection for antihypoxia or CAIX-targeted treatment.

PD-L1 microSPECT/CT Imaging for Longitudinal Monitoring of PD-L1 Expression in Syngeneic and Humanized Mouse Models for Cancer.

Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive responses in subgroups of patients with cancer. PD-L1 expression in tumors seems to be a prerequisite for treatment response. However, PD-L1 is heterogeneously expressed within tumor lesions and may change upon disease progression and treatment.