Fibroblast activation protein (FAP) is overexpressed in cancer associated fibroblasts of several tumor entities. Recent development of quinoline based positron-emission-tomography (PET)-tracers that act as FAP-Inhibitors (FAPI) demonstrated promising results preclinically and already also in few clinical cases. Consecutively this novel tracer is now applied in our hospital to amend the diagnostics of cancer patients facing limitations of standard exams. Here we analyze the tissue biodistribution and preliminary dosimetry of two members of this new class of PET-radiopharmaceuticals. A preliminary dosimetry estimate for FAPI-02 and FAPI-04 was based on two patients examined at 0.2h, 1h and 3h after tracer injection using the QDOSE dosimetry software suit. Further PET/CT scans of tumor patients were acquired 1 h after injection of either FAPI-02 ( = 25) or FAPI-04 ( = 25); for 6 patients an intra-individual related FDG-scan (also acquired 1h p.i.) was available. For the normal tissue of 16 organs, a 2 cm Spheric-VOI was placed in the parenchyma, for tumor lesions a threshold segmented VOI was used to quantify SUVmean/max. Very similar to literature values forF-FDG, Ga-DOTATATE orGa-PSMA-11, an exam with 200 MBq Ga-FAPI-2/4 corresponds to an equivalent dose of approx. 3-4 mSv. After a fast clearance via the kidneys the normal organs showed a low tracer uptake with only minimal changes between 10 min and 3 h p.i.. In FAPI-02 the tumor uptake from 1h to 3h p.i. decreased by 75%, whereas the tumor retention was prolonged with FAPI-04 (25% washout). Regarding tumor-to-background ratios, at 1h p.i. both FAPI-tracers performed equally. In comparison to FDG the tumor uptake was almost equal (average SUV-FDG 7.41; SUV-FAPI-2 7.37; n.s.); the background uptake in brain (11.01 vs 0.32), liver (2.77 vs 1.69) and oral/pharyngeal mucosa (4.88 vs 2.57) was significantly lower with FAPI; other organs were not relevantly different between FDG and FAPI. FAPI-PET/CT is a new diagnostic method in imaging cancer patients. In contrast to FDG no diet/fasting in preparation of the exam is necessary and image acquisition can potentially be started few minutes after tracer application. Tumor-to-background contrast ratios were equal or even improved in comparison to FDG.

PurposeThe prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer 68Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, 68Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of 18F-labelled analogs. 18F-PSMA-1007 was selected among several 18F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of 18F-PSMA-1007 in human volunteers and patients.MethodsRadiation dosimetry of 18F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent 18F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining.ResultsWith an effective dose of approximately 4.4–5.5 mSv per 200–250 MBq examination, 18F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other 18F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, 18F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to 18F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2–3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. 18F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter.Conclusion 18F-PSMA-1007 performs at least comparably to 68Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of 68Ga-labelled PSMA-targeted tracers.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-016-3573-4) contains supplementary material, which is available to authorized users.

Purpose The aims of this study were to develop a prostate-specific membrane antigen (PSMA) ligand for labelling with different radioisotopes of lead and to obtain an approximation of the dosimetry of a simulated 212 Pb-based alpha therapy using its 203 Pb imaging analogue. Methods Four novel Glu-urea-based ligands containing the chelators p -SCN-Bn-TCMC or DO3AM were synthesized. Affinity and PSMA-specific internalization were studied in C4-2 cells, and biodistribution in C4-2 tumour-bearing mice. The most promising compound, 203 Pb-CA012, was transferred to clinical use. Two patients underwent planar scintigraphy scans at 0.4, 4, 18, 28 and 42 h after injection, together with urine and blood sampling. The time–activity curves of source organs were extrapolated from 203 Pb to 212 Pb and the calculated residence times of 212 Pb were forwarded to its unstable daughter nuclides. QDOSE and OLINDA were used for dosimetry calculations. Results In vitro, all ligands showed low nanomolar binding affinities for PSMA. CA09 and CA012 additionally showed specific ligand-induced internalization of 27.4 ± 2.4 and 15.6 ± 2.1 %ID/10 6 cells, respectively. The 203 Pb-labelled PSMA ligands were stable in serum for 72 h. In vivo, CA012 showed higher specific uptake in tumours than in other organs, and particularly showed rapid kidney clearance from 5.1 ± 2.5%ID/g at 1 h after injection to 0.9 ± 0.1%ID/g at 24 h. In patients, the estimated effective dose from 250–300 MBq of diagnostic 203 Pb-CA012 was 6–7 mSv. Assuming instant decay of daughter nuclides, the equivalent doses projected from a therapeutic activity of 100 MBq of 212 Pb-CA012 were 0.6 Sv RBE5 to the red marrow, 4.3 Sv RBE5 to the salivary glands, 4.9 Sv RBE5 to the kidneys, 0.7 Sv RBE5 to the liver and 0.2 Sv RBE5 to other organs; representative tumour lesions averaged 13.2 Sv RBE5 (where RBE5 is relative biological effectiveness factor 5). Compared to clinical experience with 213 Bi-PSMA-617 and 225 Ac-PSMA-617, the projected maximum tolerable dose was about 150 MBq per cycle. Conclusion 212 Pb-CA012 is a promising candidate for PSMA-targeted alpha therapy of prostate cancer. The dosimetry estimate for radiopharmaceuticals decaying with the release of unstable daughter nuclides has some inherent limitations, thus clinical translation should be done cautiously. Electronic supplementary material The online version of this ...

Introduction PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties. Methods Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120–160 μg) [177Lu]Lu-PSMA-ALB-56 followed by whole-body SPECT/CT imaging over 7 days. Volumes of interest were defined on the SPECT/CT images for dosimetric evaluation for healthy tissue and tumor lesions. General safety and therapeutic efficacy were assessed by measuring blood biomarkers. Results [177Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177Lu]Lu-PSMA-ALB-56 in the blood with the highest uptake in tumor lesions at 48 h post injection. Compared with published data for other therapeutic PSMA radioligands (e.g. PSMA-617 and PSMA I&T), normalized absorbed doses of [177Lu]Lu-PSMA-ALB-56 were up to 2.3-fold higher in tumor lesions (6.64 ± 6.92 Gy/GBq) and similar in salivary glands (0.87 ± 0.43 Gy/GBq). Doses to the kidneys and red marrow (2.54 ± 0.94 Gy/GBq and 0.29 ± 0.07 Gy/GBq, respectively) were increased. Conclusion Our data demonstrated that the concept of albumin-binding PSMA-radioligands is feasible and leads to increased tumor doses. After further optimization of the ligand design, the therapeutic outcomes may be improved for patients with prostate cancer.