Abstract Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive antitumor activity. Patients with tumors expressing PD-L1 are most likely to respond this treatment. The aim of our study was develop a noninvasive imaging technique determine tumor expression in vivo. This could allow selection patients benefit from anti–PD-1/PD-L1 treatment monitor during therapy. monoclonal antibody PD-L1.3.1 radiolabeled Indium-111 (111In) characterized...

Prostate-specific membrane antigen (PSMA) is a well-established target for nuclear imaging and therapy of prostate cancer (PCa).Radiolabeled small-molecule PSMA inhibitors are excellent candidates PCa theranostics-they rapidly efficiently localize in tumor lesions.However, high tracer uptake kidneys salivary glands major concerns therapeutic applications.Here, we present the preclinical application I&T, DOTAGA-chelated urea-based inhibitor, SPECT/CT radionuclide PCa. 111 In-PSMA I&T showed...

The insulinlike growth factor 1 receptor (IGF-1R) is a new target for the treatment of breast cancer. Patients with cancer lesions that express IGF-1R may benefit from anti-IGF-1R antibodies. Therefore, aim present study was to develop noninvasive, in vivo imaging method, using radiolabeled antibodies, visualize expression.R1507 monoclonal antibody directed against IGF-1R. In vitro, affinity and internalization kinetics (111)In-R1507 were determined IGF-1R-expressing triple-negative cell...

Abstract Increasing attention is given to personalized tumour therapy, where α-emitters can potentially play an important role. Alpha particles are ideal for localized cell killing because of their high linear energy transfer and short ranges. However, upon the emission α particle daughter nuclide experiences a recoil large enough ensure decoupling from any chemical bond. These ‘free’ nuclides no longer targeted accumulate in normal tissue. In this paper, we used polymersomes as model...

Bevacizumab (antivascular endothelial growth factor [anti‐VEGF]) and cetuximab (antiepidermal receptor [anti‐EGFR]) are approved antibodies for treatment of cancer. However, in advanced colorectal cancer, the combination fails to improve survival. As reason lack activity is unknown, our study aims determine effect bevacizumab on targeting anti‐EGFR insulin‐like 1 (IGF‐1R) tumors with single‐photon emission computed tomography (SPECT)/CT imaging. Mice subcutaneous EGFR IGF‐1R‐expressing...

Background: Up to now, prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy mainly focused on β-emitting radionuclides. Herein, two new 213Bi-labeled agents for PSMA-targeted α of prostate cancer (PCa) are reported. Methods: The biodistribution small-molecule inhibitor PSMA I&T and nanobody JVZ-008 was evaluated in mice bearing PSMA-positive LNCaP xenografts. DNA damage response followed using cells Results:In vitro, 213Bi-PSMA 213Bi-JVZ-008 led increased number...

Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. Radiation is promising approach increase response rates since it can generate anti-tumor immunity. Targeted radionuclide therapy (TRT) systemic radiation treatment, ideally suited for precision irradiation metastasized cancer. Therefore, the aim this study explore potential combined TRT, targeting carbonic anhydrase IX...

Noninvasive imaging of the epidermal growth factor receptor (EGFR) in head-and-neck squamous cell carcinoma could be value to select patients for EGFR-targeted therapy. We assessed dose optimization (111) Indium-DTPA-cetuximab ((111) In-cetuximab) EGFR a xenograft model. In-cetuximab slowly internalized into FaDu cells vitro, amounting 1.0 × 10(4) molecules cetuximab per after 24 hr (15.8% added activity). In nude mice with subcutaneous tumors, protein escalation study showed highest...

Pretargeted radioimmunotherapy (PRIT) with the β-emitting radionuclide ¹⁷⁷Lu is an attractive approach to treat carcinoembryonic antigen (CEA)–expressing tumors. The therapeutic efficacy of PRIT might be improved using α-emitting radionuclides such as ²¹³Bi. Herein, we report and compare tumor-targeting properties ²¹³Bi for CEA-expressing xenografts, bispecific monoclonal antibody TF2 (anti-CEA × anti–histamine-succinyl-glycine [HSG]) di-HSG-DOTA peptide...

Abstract Purpose: To investigate whether indium-111–labeled R1507 (111In-R1507) immuno-SPECT (single—photon emission computed tomography), a novel noninvasive, in vivo screening method to visualize membranous insulin-like growth factor 1 receptor (IGF-1R) expression and accessibility, can be used predict IGF-1R treatment (R1507) response bone sarcomas. Experimental Design: BALB/c nude mice were subcutaneously implanted with IGF-1R–expressing human sarcoma xenografts (OS-1, EW-5, EW-8) which...

The insulin-like growth factor 1 receptor (IGF-1R) is a potential new target for the treatment of breast cancer. Patients with cancer lesions that express IGF-1R may benefit from anti-IGF-1R antibodies. expression can be visualized using radiolabeled R1507, monoclonal antibody directed against IGF-1R. However, antibodies clear slowly circulation, resulting in low tumor-to-background ratios early after injection. Therefore, we aimed to accelerate targeting R1507 F(ab')2 and Fab fragments. In...

Introduction The insulin-like growth factor 1 receptor (IGF-1R) may be involved in the development of resistance against conventional cancer treatment. aim this study was to assess whether IGF-1R expression breast tumors changes during neoadjuvant therapy and these were associated with survival. Methods Paraffin embedded tumor tissue collected from pretreatment biopsies surgical resections 62 patients who treated chemotherapy or endocrine therapy. determined immunohistochemically compared...

Abstract 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 tumors seems to be a prerequisite for treatment response. However, is heterogeneously expressed within tumor lesions may change upon disease progression treatment. Imaging could aid patient selection. Previously, we showed feasibility image PD-L1+ immunodeficient mice. also on immune cell subsets. Therefore,...

Background CD3 bispecific antibodies (CD3-bsAbs) require binding of both a tumor-associated surface antigen and for their immunotherapeutic effect. Their efficacy is, therefore, influenced by the tumor uptake extracellular dose. To optimize currently limited in solid tumors, increased understanding pharmacokinetics vivo internalization is needed. Methods Here, were studied CD3xTRP1, fully murine Fc-inert bsAb, endogenous TRP1-expressing immunocompetent male C57BL/6J mice bearing...

The use of nanoparticles as tumor-targeting agents is steadily increasing, and the influence nanoparticle characteristics such size stealthiness have been established for a large number nanocarrier systems. However, not much known about impact tumor presence on circulation times. This paper reports in vivo time biodistribution polybutadiene-polyethylene oxide (PBd-PEO) polymersomes. For this purpose, polymersomes were loaded with gamma-emitter

Abstract Purpose Angiogenesis plays an important role in the growth and metastatic spread of solid tumours is characterised by expression integrins on cell surface endothelial cells. Radiolabelled RGD peptides specifically target angiogenesis-related α v β 3 integrins, expressed activated cells sprouting blood vessels. Here, we validated feasibility 68 Ga[Ga]-DOTA-E-[c(RGDfK)] 2 ( Ga-RGD) PET/CT to visualise angiogenesis patients with oral squamous carcinoma (OSCC). Methods Ten OSCC...

Prostate cancer (PCa) is the most common in men worldwide. In general, PCa responds poorly to chemotherapy. Therefore, antibody-drug conjugates (ADCs) have been developed specifically deliver highly cytotoxic drugs tumor. Because prostate-specific membrane antigen (PSMA) overexpressed PCa, it represents a promising target for ADC-based therapies. The aim of this study was evaluate therapeutic efficacy site-specifically conjugated duocarmycin- and monomethyl auristatin E (MMAE)-based...

OBJECTIVES To enable preclinical testing of intravesical therapies against non‐muscle‐invasive bladder cancer (NMIBC) in an orthotopic rat tumour model, augmented by the use serial cystoscopy for vivo assessment and follow‐up. MATERIALS AND METHODS Fischer F344 rats had a 16‐G transurethral cannula placed. The mucosa was conditioned with acid rinse, followed 1‐h instillation 1.5 × 10 6 AY‐27 urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) done on day 0 (control) at 3, 4, 5,...

Abstract Background While immune checkpoint inhibitors such as anti-PD-L1 antibodies have revolutionized cancer treatment, only subgroups of patients show durable responses. Insight in the relation between clinical response, PD-L1 expression and intratumoral localization therapeutics could improve patient stratification. Therefore, we present modular synthesis multimodal antibody-based imaging tools for multiscale to study distribution therapeutics. Results To introduce modalities, a peptide...

Background Programmed death-ligand 1 (PD-L1) regulates immune homeostasis by promoting T-cell exhaustion. It is involved in chronic infections and tumor progression. Nuclear imaging using radiolabeled anti-PD-L1 antibodies can monitor PD-L1 tissue expression antibody distribution. However, physiological cause rapid clearance from blood at doses. Therefore, we hypothesized that inflammatory responses, which induce expression, affect Here, investigated the effects of three different infectious...

Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition to chemotherapy with bevacizumab did not improve survival. The reason lack activity remains unclear. aim this study was determine effect on VEGF expression targeting tumor. Mice subcutaneous SUM149 or WiDr xenografts were treated cetuximab, bevacizumab, a combination two. Before start after 7 21 days treatment, uptake radiolabeled tumor measured by immunoSPECT/CT. Tumor growth...

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. ⁶⁸Ga-labeled arginine-glycine-aspartate tripeptide sequence (RGD) PET/CT imaging may provide insight into status treatment response AVMs. This clinical feasibility study was performed demonstrate that ⁶⁸Ga-RGD can be used quantitatively assess angiogenesis peripheral...