scholarly journals Increasing molar activity by HPLC purification improves 68Ga-DOTA-NAPamide tumor accumulation in a B16/F1 melanoma xenograft model

PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0217883
Author(s):  
Jan Lennart von Hacht ◽  
Sarah Erdmann ◽  
Lars Niederstadt ◽  
Sonal Prasad ◽  
Asja Wagener ◽  
...  
Keyword(s):  
Xenograft Model ◽  
Hplc Purification ◽  
Molar Activity ◽  
Melanoma Xenograft ◽  
Tumor Accumulation

Institutional experience with nab-sirolimus in patients with malignancies harboring TSC1 or TSC2 mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3111-3111
Author(s):  
Mark Andrew Dickson ◽  
Vinod Ravi ◽  
Kristen N. Ganjoo ◽  
Gopa Iyer
Keyword(s):  
Response Rate ◽  
Xenograft Model ◽  
Low Frequency ◽  
Mtor Pathway ◽  
Serious Adverse Events ◽  
Improved Outcomes ◽  
S 100 ◽  
Institutional Experience ◽  
Tumor Accumulation ◽  
Tumor Types

3111 Background: TSC1/ TSC2 genes are tumor suppressors in the mTOR pathway; mutated at low frequency across tumor types (̃1–2%). Retrospective analyses of patients (pts) with mTOR pathway mutations treated with everolimus did not show improved outcomes vs the wild type (Voss et al. Clin Cancer Res 2019. PMID 30327302). In NCT02201212, pts with TSC1/TSC2 mutations treated with everolimus had a 7% (2/30) response rate. In the AMPECT study, pts with advanced PEComa treated with a novel mTOR inhibitor (mTORi), nab-sirolimus ( nab-S, ABI-009), the subset of pts with TSC1/TSC2 mutations had a response rate of 64% (9/14) (Wagner et al. CTOS 2020. #3463014). In a xenograft model, nab-S showed significantly higher tumor accumulation, target suppression (pS6) and antitumor activity vs everolimus or sirolimus (Hou et al. AACR 2019. #348). In an expanded access program (NCT03817515), pts with advanced tumors bearing TSC1/ TSC2 mutations were treated with nab-S and outcomes in pts with malignancies other than PEComa are reported herein. Methods: Eligible pts (ECOG 0–2) received nab-S 100 mg/m2 IV, once weekly for 2 of every 3 weeks at 3 US sites between 7/2019 and 11/2020. Results: 7 pts with TSC1/ TSC2 mutations have been consecutively enrolled and are reported here. 6/7 pts had multiple prior therapies including 2 pts previously progressing on an mTORi. 4/7 pts had partial response (PR), all in mTORi naïve pts. 2/7 pts had stable disease (SD). In 2 pts previously treated with an mTORi, 1 had SD and 1 came off treatment after 1 cycle (CA125 ↑) with no follow-up scan. Treatment-related serious adverse events (SAEs; hyperglycemia and infection) and dose reduction were reported in 1 pt with metastatic angiosarcoma; SAEs resolved and the pt continued Rx. No other SAE or dose limiting event was reported Conclusions: Patients with various malignancies bearing TSC1 or TSC2 mutations, most with progression on multiple prior therapies, showed evidence of response and manageable toxicities during treatment with nab-S. A basket trial of nab-S in malignancies with TSC1/ TSC2 mutations is planned. Clinical trial information: NCT03817515. [Table: see text]

scholarly journals Anti-tumor activity of a combination of plasminogen activator and captopril in a human melanoma xenograft model

2004 ◽  
Vol 112 (2) ◽  
pp. 329-334 ◽  
Author(s):  
Renate R.J. de Groot-Besseling ◽  
Theo J.M. Ruers ◽  
Annemieke A. van Kraats ◽  
Geert J.M. Poelen ◽  
Dirk J. Ruiter ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Xenograft Model ◽  
Human Melanoma ◽  
Human Melanoma Xenograft ◽  
Melanoma Xenograft ◽  
Anti Tumor Activity

scholarly journals Antibody Directed against Human YKL-40 Increases Tumor Volume in a Human Melanoma Xenograft Model in Scid Mice

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e95822 ◽  
Author(s):  
Johannes Salamon ◽  
Tatjana Hoffmann ◽  
Eva Elies ◽  
Kersten Peldschus ◽  
Julia S. Johansen ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Xenograft Model ◽  
Human Melanoma ◽  
Scid Mice ◽  
Human Melanoma Xenograft ◽  
Melanoma Xenograft

scholarly journals Increasing molar activity by HPLC purification improves 68Ga-DOTA-NAPamide tumor accumulation in a B16/F1 melanoma xenograft model

2019 ◽  
Author(s):  
Jan Lennart von Hacht ◽  
Sarah Erdmann ◽  
Lars Niederstadt ◽  
Sonal Prasad ◽  
Asja Wagener ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Xenograft Model ◽  
Positron Emission Tomography Imaging ◽  
Peptide Receptor Radionuclide Therapy ◽  
Melanocortin Receptor ◽  
Target Tissue ◽  
Tumor Uptake ◽  
Molar Activity ◽  
Biodistribution Studies ◽  
Unlabeled Peptide

AbstractPurposeMelanocortin receptor 1 is overexpressed in melanoma and may be a molecular target for imaging and peptide receptor radionuclide therapy. 68Gallium labeling of DOTA-conjugated peptides is an established procedure in the clinic for use in positron emission tomography imaging. Aim of this study was to compare a standard labeling protocol against the 68Ga-DOTA peptide purified from the excess of unlabeled peptide.ProceduresThe MC1R ligand DOTA-NAPamide was labeled with 68Ga using a standard clinical protocol. Radioactive peptide was separated from the excess of unlabeled DOTA-NAPamide by HPLC. Immediately after the incubation of peptide and 68Ga (95 °C, 15 min), the reaction was loaded on a C18 column and separated by a water/acetonitrile gradient, allowing fractionation in less than 20 minutes. Radiolabeled products were compared in biodistribution studies and PET imaging using nude mice bearing MC1R-expressing B16/F1 xenograft tumors.ResultsIn biodistribution studies, the non-purified 68Ga-DOTA-NAPamide did not show significant uptake in the tumor at 1 h post injection (0.78% IA/g). By the additional HPLC step, the molar activity was raised around 10,000-fold by completely removing unlabeled peptide. Application of this rapid purification strategy led to a more than 8-fold increase in tumor uptake (7.0% IA/g). The addition of various amounts of unlabeled DOTA-NAPamide to the purified product led to a blocking effect and a decreased specific tumor uptake, similar to the result seen with non-purified radiopeptide. PET imaging was performed using the same tracers for biodistribution. Purified 68Ga-DOTA-NAPamide, in comparison, showed superior tumor uptake.ConclusionsWe demonstrated that chromatographic separation of radiolabeled from excess unlabeled peptide is technically feasible and beneficial, even for short-lived isotopes such as 68Ga. Unlabeled peptide molecules compete with receptor binding sites in the target tissue. Purification of the radiopeptide therefore improved tumor uptake.

scholarly journals 18F-Labeled Cyclized α-Melanocyte-Stimulating Hormone Derivatives for Imaging Human Melanoma Xenograft with Positron Emission Tomography

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chengcheng Zhang ◽  
Zhengxing Zhang ◽  
Helen Merkens ◽  
Jutta Zeisler ◽  
Nadine Colpo ◽  
...  
Keyword(s):  
Human Melanoma ◽  
Image Contrast ◽  
Post Injection ◽  
Tumor Uptake ◽  
Isotope Exchange Reaction ◽  
Melanocyte Stimulating Hormone ◽  
Molar Activity ◽  
Human Melanoma Xenograft ◽  
Melanoma Xenograft ◽  
Stimulating Hormone

Abstract Since metastatic melanoma is deadly, early diagnosis thereof is crucial for managing the disease. We recently developed α-melanocyte-stimulating hormone (αMSH) derivatives, [68Ga]Ga-CCZ01048 and [18F]CCZ01064, that target the melanocortin 1 receptor (MC1R) for mouse melanoma imaging. In this study, we aim to evaluate [18F]CCZ01064 as well as a novel dual-ammoniomethyl-trifluoroborate (AmBF3) derivative, [18F]CCZ01096, for targeting human melanoma xenograft using μPET imaging. The peptides were synthesized on solid phase using Fmoc chemistry. Radiolabeling was achieved in a one-step 18F-19F isotope-exchange reaction. μPET imaging and biodistribution studies were performed in NSG mice bearing SK-MEL-1 melanoma xenografts. The MC1R density on the SK-MEL-1 cell line was determined to be 972 ± 154 receptors/cell (n = 4) via saturation assays. Using [18F]CCZ01064, moderate tumor uptake (3.05 ± 0.47%ID/g) and image contrast were observed at 2 h post-injection. Molar activity was determined to play a key role. CCZ01096 with two AmBF3 motifs showed comparable sub-nanomolar binding affinity to MC1R and much higher molar activity. This resulted in improved tumor uptake (6.46 ± 1.42%ID/g) and image contrast (tumor-to-blood and tumor-to-muscle ratios were 30.6 ± 5.7 and 85.7 ± 11.3, respectively) at 2 h post-injection. [18F]CCZ01096 represents a promising αMSH-based μPET imaging agent for human melanoma and warrants further investigation for potential clinical translation.

scholarly journals Nanoparticles Functionalized with Collagenase Exhibit Improved Tumor Accumulation in a Murine Xenograft Model

2014 ◽  
Vol 31 (12) ◽  
pp. 1307-1312 ◽  
Author(s):  
Surya Murty ◽  
Taylor Gilliland ◽  
Peter Qiao ◽  
Tate Tabtieng ◽  
Elizabeth Higbee ◽  
...  
Keyword(s):  
Xenograft Model ◽  
Murine Xenograft Model ◽  
Tumor Accumulation
Sign in / Sign up

Export Citation Format

Share Document