Radiosynthesis and validation of [Carboxy‐¹¹C]4‐Aminobenzoic acid ([¹¹C]PABA), a PET radiotracer for imaging bacterial infections

Abstract

In this practitioner protocol, the radiochemical synthesis of [ C] PABA is described in detail, and a quality control summary of three validation productions is presented. The results indicate that the radiotracer product can be produced in good radiochemical yield (14% at end-of-synthesis (EOS)) at high specific activity (molar activity 11 Ci/μmole EOS; 407 GBq/μmole) and high chemical and radiochemical purity as a sterile, pyrogen-free solution suitable for injection conforming to current Good Manufacturing Practice (cGMP) requirements.

11C-PABA as a PET Radiotracer for Functional Renal Imaging: Preclinical and First-in-Human Study

“…11 C-PABA was synthesized as a sterile, pyrogen-free solution with high radiochemical purity and specific activity (163.7 ± 40.9 GBq/µmol) under current good manufacturing practices (cGMP) conditions at the Johns Hopkins Hospital PET center (16).…”

11C-Para-aminobenzoic acid PET imaging of S. aureus and MRSA infection in preclinical models and humans

“…Radiochemical synthesis of 11 C-PABA. 11 C-PABA was synthesized at the Johns Hopkins Hospital and UCSF PET radiotracer facilities as a sterile, pyrogen-free solution with high radiochemical purity and specific activity as previously described (34). For human studies, the 11 C-PABA radiosynthesis at Johns Hopkins followed good-manufacturing practices.…”

Radiotracer Development for Bacterial Imaging

“…(A) 11 C-PABA is prepared by nucleophilic addition of a Grignard reagent to cyclotron-generated 11 CO 2 . 32 (B) 2-18 F-PABA can be prepared in three steps by nucleophilic aromatic substitution with 18 F-fluoride, followed by hydrolysis of a nitrile to carboxylic acid, and reduction of a nitro group to a primary amine. 15 (C) 18 F-FPTMP is radiolabeled in a one-pot two-step reaction by nucleophilic substitution of the boc-protected mesylate precursor followed by acidic deprotection.…”

“…3 H-PABA was found to accumulate in bacteria following a small molecule screening, and it was subsequently developed as a PET radiotracer using carbon-11 ( 11 C, half-life = 20.4 min, β + 99.8%, E max = 960 keV) Figure A) . In a mouse model of E.…”

“…7 11 C-PABA was synthesized via cyclotron generated 11 CO 2 and a commercially available Grignard precursor (Figure 3A). 32 In a mouse model of E. coli infection, the uptake of 11 C-PABA in infected tissue was 2.6-fold higher than in the inflamed control tissue inoculated with heat-killed bacteria. 13 The PABA analogue 2fluoro-PABA was found to be a suitable alternative substrate for tetrahydrofolate and was subsequently developed as a radiotracer using 18 F. 2-18 F-PABA was obtained in three steps by conventional nucleophilic aromatic substitution radiofluorination of the commercially available precursor 2,4dinitrolzenzonitrile (Figure 3B).…”