Abstract
1642
Objectives: [11C]Trimethoprim, [11C]TMP, is a radiolabeled positron emission tomography (PET) imaging agent that has been studied in animals to image genetically engineered cells and bacterial infection. [11C]TMP is chemically based on the well-studied and often clinically used antibiotic, trimethoprim. The protein target of TMP is bacterial dihydrofolate reductase (DHFR), and successful in vitro and in rodent models show that [11C]TMP accumulates in tissues containing bacterial DHFR, such as sites of bacterial infection or sites with genetically engineered cells that carry the bacterial DHFR transgene. The purpose of this protocol to evaluate the first-in-human biodistribution and dosimetry of uptake of [11C]TMP in human subjects with PET/CT.
Methods: Three male human volunteers (ages 47-69, mean 60) underwent three serial PET whole body and up to three low dose CT attenuation scans in a Philips Ingenuity PET/CT scanner following injection of [11C]TMP (mean 418 MBq, 217-797 MBq (11.3 mCi, 5.9-21.5 mCi)). Patients provided informed consent for studies according to guidelines of University of Pennsylvania Institutional Review Board (IRB). Total activity residing in brain, gallbladder, heart contents, intestines, kidneys, liver, lumbar vertebrae, lungs, pancreas, salivary glands, spleen, thyroid and urinary bladder were measured from PET images via MIM version 6.7 (MIM Software Inc.). Activity in red marrow was calculated using activity concentrations in lumbar vertebrae 2, 3, and 4. Time activity curves for assessed organs were generated and fit to mono- or bi-exponential functions and dosimetry estimates were calculated using the Standard Adult Male phantom option in OLINDA ❘ EXM v1.1 software. Absorbed dose in the salivary glands was calculated according to Herrmann et al. (JNM 2015; 56:855-861).
Results: The highest mean organ doses in descending order were: kidneys (1.45E-02 mSv/MBq); liver (1.44E-02 mSv/MBq); urinary bladder wall (1.13E-02 mSv/MBq); spleen (9.87E-03mSv/MBq); small intestine (8.24E-03mSv/MBq); pancreas (5.57E-03 mSv/MBq); and lungs (5.56E-03mSv/MBq). The effective dose was 4.44E-03 mSv/MBq. An anticipated maximum injected dose of 925 MBq (25 mCi) will yield an effective dose of 4.1 mSv, and estimated absorbed doses of 13.4 mSv in the kidneys and 9.1 mSv in the blood-forming spleen, which is below the applicable Radioactive Drug Research Committee guidelines of a single 30 mSv dose and total annual dose of 50 mSv for blood-forming organs.
Conclusions: A maximum anticipated injected dose of 925 MBq of [11C]TMP yields an average dose of 13.4 mSv in the highest uptake organ (kidneys), 9.1 mSv in the spleen and an effective dose of 4.1 mSv and confirmed expectations that levels of absorbed doses were adequately low to allow multiple [11C]TMP PET scans of the same patient each year to allow monitoring of active infections and treatment responses. Research Support: RKD is supported by K01DA040023, MAS is supported by the NIH Office of the Director Early Independence Award (DP5-OD26386), the Burroughs Wellcome Fund Career Award for Medical Scientists.
