Related Experiment Video
Updated: Feb 1, 2026
Focal Laser Ablation of Prostate Cancer: An Office Procedure
Published on: March 30, 2021
Development of an automated one-step radiolabeling procedure for a PSMA-targeted radiotherapeutic for prostate cancer
Meltem Ocak1, Kanishka Sikligar2, Michael Pun2
1Molecular Imaging and Theranostics Center, Columbia, MO, 65211, USA.
Background:
CTT1403 (177Lu-CTT2001), an irreversible phosphoramidate PSMA inhibitor developed by Cancer Targeted Technology, was initially synthesized using a two-step radiolabeling method and has previously been evaluated in first-in-human studies. This two-step approach protected the phosphoramidate pharmacophore-containing a temperature- and pH-labile PN bond-from the harsh conditions required for lutetium-177 (177Lu) chelation. Although the final chemical structure of CTT1403 is identical regardless of the radiolabeling route, it was not clear that CTT2001 could tolerate one-step labeling conditions while preserving PSMA-binding integrity. Therefore, the aim of the study was to develop, optimize, and automate a one-step radiolabeling method for CTT1403 and to confirm that the resulting product is biologically equivalent and exhibits comparable in vitro and in vivo behavior to CTT1403 produced by the original two-step process.
Methods:
CTT2001 was synthesized and radiolabeled with 177Lu using an optimized one-step procedure that was subsequently automated on a Trasis AllinOne synthesizer. Radiochemical purity, stability, cellular uptake/internalization, and biodistribution in PC3-PIP tumor-bearing mice were evaluated.
Results:
CTT1403 synthesized via the one-step method demonstrated cellular uptake and internalization in PC3-PIP cells, as well as in vivo biodistribution in PC3-PIP tumor-bearing mice, that were comparable to those of the two-step-labeled product. The one-step procedure was successfully automated on the Trasis All-in-One synthesizer, producing CTT1403 with a radiochemical yield of 86.5 ± 4.27% (n = 3), a molar activity of 30.3 ± 1.11 MBq/nmol, and a radiochemical purity of 97.6 ± 0.80% (n = 3) in a total synthesis time of 38 min. The final product remained stable for at least 24 h at -4 °C and -20 °C.
Conclusions:
The one-step radiolabeling method yields CTT1403 that is biologically equivalent to the two-step product and can be reliably produced using fully automated synthesis. This streamlined, efficient, and reproducible approach supports routine clinical manufacturing of CTT1403.
Insights
A new one-step radiolabeling method for CTT1403 (177Lu-CTT2001) produces a product biologically equivalent to the original two-step method. This automated process streamlines production for clinical use.
Area of Science:
- Radiopharmaceutical chemistry
- Nuclear medicine
- Oncology
Background:
- CTT1403 (177Lu-CTT2001) is an irreversible phosphoramidate PSMA inhibitor.
- Previous synthesis involved a two-step radiolabeling method to protect a labile bond.
- The integrity of CTT1403 under one-step labeling conditions was unconfirmed.
Purpose of the Study:
- Develop and optimize a one-step radiolabeling method for CTT1403.
- Automate the one-step synthesis process.
- Confirm biological equivalence of one-step versus two-step CTT1403.
Main Methods:
- Synthesized and radiolabeled CTT2001 with 177Lu using an optimized one-step procedure.
- Automated the process on a Trasis AllinOne synthesizer.
- Evaluated radiochemical purity, stability, cellular uptake/internalization, and biodistribution in PC3-PIP tumor models.
Main Results:
- One-step CTT1403 showed comparable cellular uptake and in vivo biodistribution to the two-step product.
- Automated synthesis yielded 86.5 ± 4.27% radiochemical yield and 97.6 ± 0.80% purity in 38 minutes.
- The product demonstrated stability for at least 24 hours at low temperatures.
Conclusions:
- The one-step radiolabeling method produces biologically equivalent CTT1403.
- Fully automated synthesis ensures reliable and reproducible production.
- This streamlined approach supports routine clinical manufacturing of CTT1403.
Related Concept Videos
01:19Handwashing II: Pre-procedure and Initial Procedure Steps
The hand washing procedure itself includes the following steps. First, cover cuts, if any, on hands with a waterproof dressing. Cuts and abrasions can become contaminated with bacteria hindering the ability to clean the area thoroughly. In addition, repeated hand washing can worsen an injury. The nails must be short and clean, without nail...
01:15Handwashing III: During the Procedure and Post-Procedure Steps
01:26Tracheostomy Suctioning I: Pre-Procedural Steps
Equipment Required
First, gather all necessary equipment: a sterile suction catheter, a sterile disposable container, sterile gloves, a towel or...
01:16Tracheostomy Care I: Pre-procedural Steps
Required Equipment
The equipment necessary for tracheostomy care includes:
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
03:08Rate-Determining Steps
In a multistep reaction mechanism, one of the elementary steps progresses significantly slower than the others. This slowest step is called the rate-limiting step (or rate-determining step). A reaction cannot proceed faster than its slowest step, and hence, the rate-determining step limits the overall reaction rate.
The concept of rate-determining step can be understood from the analogy of a 4-lane freeway with a short-stretch of traffic-bottleneck caused due to...