Initial Evaluation of [18F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer

Abstract

Purpose Prostate-specific membrane antigen (PSMA) is a recognized target for imaging prostate cancer. Here we present initial safety, biodistribution, and radiation dosimetry results with [18F]DCFPyL, a second-generation fluorine-18-labeled small-molecule PSMA inhibitor, in patients with prostate cancer. Procedures Biodistribution was evaluated using sequential positron-emission tomography (PET) scans in nine patients with prostate cancer. Time-activity curves from the most avid tumor foci were determined. The radiation dose to selected organs was estimated using OLINDA/EXM. Results No major radiotracer-specific adverse events were observed. Physiologic accumulation was observed in known sites of PSMA expression. Accumulation in putative sites of prostate cancer was observed (SUVmax up to >100, and tumor-to-blood ratios up to >50). The effective radiation dose from [18F]DCFPyL was 0.0139 mGy/MBq or 5 mGy (0.5 rem) from an injected dose of 370 MBq (10 mCi). Conclusions [18F]DCFPyL is safe with biodistribution as expected, and its accumulation is high in presumed primary and metastatic foci. The radiation dose from [18F]DCFPyL is similar to that from other PET radiotracers.

The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions

“…For instance, a low-dose 68 Ga-PSMA-617 PET/CT with an administered activity of 203 MBq results in an effective overall dose of 4.3 mSv (PET) 1 3.5 mSv (lowdose CT), which equals 7.8 mSv. These results are similar compared with other most recently introduced PSMA ligands (14,33).…”

“…In addition, the availability of cyclotron-based 18 F is significantly higher than the generator-based 68 Ga. Most recently, the team of Martin Pomper introduced an 18 F-labeled PSMA ligand, 18 F-DCFPyL (14). Few PCa lesions decreased in SUV and contrast in later images (Fig.…”

“…During the last 2 decades, many efforts have been undertaken to develop PSMA ligands (8)(9)(10)(11)(12)(13)(14)(15)(16). One of these ligands, the smallmolecule Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)], also known as PSMA-11, PSMA HBED , Glu-CO-Lys(Ahx)-HBED-CC, DKFZ-PSMA-11, PSMA-HBED-CC, PSMA-HBED, PSMA, or Prostamedix, developed at the German Cancer Research Center Heidelberg (DKFZ), has become the most clinically used radiotracer.…”

Glu-Ureido–Based Inhibitors of Prostate-Specific Membrane Antigen: Lessons Learned During the Development of a Novel Class of Low-Molecular-Weight Theranostic Radiotracers

“…Tracer accumulation in normal organs, such as the salivary and lacrimal glands, the kidneys, the spleen, and the intestines (which is not directly comparable to the preclinical in vivo and ex vivo results [lesson 3]), must be assessed in patients as well, especially from the safety (radiation dosimetry) perspective. The outcome of such assessments (18,26,29,40,(93)(94)(95)(96)(97) will show whether future generations of PSMA radioligands should still be considered for first-inhuman studies or whether efforts targeting new complementary molecules should be undertaken to further increase the efficacy of the diagnosis and treatment of PC.…”

Reply: PSMA Ligands for Imaging Prostate Cancer: Alternative Labeling by Complex Formation with Al18F2+

“…We also gratefully acknowledge their comments on our articles (1,2) questioning the need for radiofluorinated PSMA PET tracers in addition to the 68 Ga-labeled versions already available as a diagnostic version of theranostic ligands, and we appreciate their perspective on 18 F-labeled PSMA tracers. Indeed, in recent years several 18 F-labeled PSMA radioligands apart from the mentioned 18 F-AlF 21 -labeled variants have already been introduced both preclinically and clinically (3)(4)(5). Particularly, Szabo et al (4) clinically introduced 18 F-DCFPyL, an improved second-generation 18 F-PSMA ligand, which was followed by the work of further optimized next-generation PET tracer 18 F-PSMA-1007 recently introduced by Giesel et al (5).…”