The purpose of this study was to evaluate the accuracy of Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)] PET compared with morphologic imaging for the assessment of lymph node metastases (LNM) in patients with recurrent prostate cancer. Methods: Forty-eight patients (median age, 71 y; interquartile range, 66-74 y) with biochemical recurrence (median prostate-specific antigen level, 1.31 ng/mL; interquartile range, 0.75-2.55 ng/mL) who underwent 68 Ga-prostate-specific membrane antigen (PSMA) HBED-CC PET/CT or PET/MR and salvage lymphadenectomy were retrospectively included. Institutional review board approval and written informed consent were obtained from all patients for the purpose of anonymized evaluation and publication of their data. Standardized predefined lymph node (LN) template fields (n 5 10) were evaluated in 68 Ga-PSMA HBED-CC PET and morphologic imaging for the presence of LNM using a 5-point-scale. Additionally, SUV mean/max and size of suspicious lesions were determined. Specificity of 68 Ga-PSMA HBED-CC PET imaging for PET-positive LNs was defined by comparison to histopathology. The diagnostic accuracy of 68 Ga-PSMA HBED-CC PET compared with morphologic imaging alone was assessed, and areas under the receiver-operating-characteristic curves are presented. Results: LNM were found histologically in 68 of 179 resected anatomic LN fields (38.0%). The specificity of 68 Ga-PSMA HBED-CC PET and morphologic imaging was 97.3% and 99.1%, respectively. However, 68 Ga-PSMA HBED-CC PET detected LNM in 53 of 68 histopathologically proven metastatic LN fields (77.9%) whereas morphologic imaging was positive in only 18 of 67 (26.9%). 68 Ga-PSMA HBED-CC PET imaging performed significantly superior to morphologic imaging for detection of LNM (difference in the areas under the receiver-operating-characteristic curves, 0.139; 95% confidence interval, 0.063-0.214; P , 0.001). In 68 Ga-PSMA HBED-CC PET, the mean size of PET-positive LN measured by CT or MRI was 8.3 ± 4.3 mm (range, 4-25 mm), and LNs, which were suspicious only in CT or MRI, presented with a mean size of 13.0 ± 4.9 mm (range, 8-25 mm). Conclusion: 68 Ga-PSMA HBED-CC PET imaging is a promising method for early detection of LNM in patients with biochemical recurrent prostate cancer. It is more accurate than morphologic imaging and thus might represent a valuable tool for guiding salvage lymphadenectomy.

CXCR4 is a chemokine receptor that is overexpressed in various human cancers and is involved in tumor metastasis. The aim of this proof-of-concept study was to evaluate a novel CXCR4-targeted PET probe in patients with solid cancers with reported in vitro evidence of CXCR4 overexpression and to estimate its potential diagnostic value. Methods: Twenty-one patients with histologically proven pancreatic cancer, laryngeal cancer, non-small cell lung cancer, prostate cancer, melanoma, breast cancer, hepatocellular carcinoma, glioblastoma, sarcoma, or cancer of unknown primary underwent PET imaging using the novel CXCR4 nuclear probe 68 Ga-pentixafor. The SUV max of the liver, spleen, and bone marrow was measured to determine physiologic tracer distribution. For evaluation of tracer accumulation in solid cancers, SUV max and tumor-tobackground (T/B) ratios were determined in a total of 43 malignant lesions, including 8 primary tumors, 3 locally recurrent tumors, and 32 metastases. When available, the SUV max of malignant lesions was compared with the corresponding SUV max measured in routine 18 F-FDG PET. Results: Moderate tracer accumulation was detectable in the liver, bone marrow, and spleen, with a mean SUV max of 3.1, 3.7, and 5.6, respectively. By visual interpretation criteria, 9 of 11 primary and locally recurrent tumors were detectable, exhibiting a mean SUV max of 4.7 (range, 2.1-10.9) and a mean T/B ratio of 2.9. Twenty of 32 evaluated metastases were visually detectable (mean SUV max , 4.5 [range, 3.2-13.8]; mean T/B ratio, 2.8). The highest signal was detected in a patient with non-small cell lung cancer (SUV max , 10.9; T/B ratio, 8.4) and a patient with cancer of unknown primary (SUV max , 13.8; T/B ratio, 8.1). Compared with 18 F-FDG PET, which was additionally performed in 10 patients, 68 Gapentixafor PET had a lower SUV max in all measured malignant lesions. Conclusion: On the basis of these first observations in a small and heterogeneous patient cohort, the in vitro CXCR4 expression profile of solid cancers and metastases described in the previous literature does not seem to sufficiently depict the in vivo distribution revealed by CXCR4-targeted PET. Moreover, the detectability of solid cancers seems to be generally lower for 68 Ga-pentixafor than for 18 F-FDG PET.

The glutamic acid derivative (S)-4-(3-18 F-Fluoropropyl)-L-glutamic acid ( 18 F-FSPG, alias BAY 94-9392), a new PET tracer for the detection of malignant diseases, displayed promising results in non-small cell lung cancer patients. The aim of this study was to provide dosimetry estimates for 18 F-FSPG based on human whole-body PET/CT measurements. Methods: 18 F-FSPG was prepared by a fully automated 2-step procedure and purified by a solid-phase extraction method. PET/CT scans were obtained for 5 healthy volunteers (mean age, 59 y; age range, 51-64 y; 2 men, 3 women). Human subjects were imaged for up to 240 min using a PET/CT scanner after intravenous injection of 299 6 22.5 MBq of 18 F-FSPG. Image quantification, timeactivity data modeling, estimation of normalized number of disintegrations, and production of dosimetry estimates were performed using the RADAR (RAdiation Dose Assessment Resource) method for internal dosimetry and in general concordance with the methodology and principles as presented in the MIRD 16 document. Results: Because of the renal excretion of the tracer, the absorbed dose was highest in the urinary bladder wall and kidneys, followed by the pancreas and uterus. The individual organ doses (mSv/MBq) were 0.40 6 0.058 for the urinary bladder wall, 0.11 6 0.011 for the kidneys, 0.077 6 0.020 for the pancreas, and 0.030 6 0.0034 for the uterus. The calculated effective dose was 0.032 6 0.0034 mSv/MBq. Absorbed dose to the bladder and the effective dose can be reduced significantly by frequent bladder-voiding intervals. For a 0.75-h voiding interval, the bladder dose was reduced to 0.10 6 0.012 mSv/MBq, and the effective dose was reduced to 0.015 6 0.0010 mSv/MBq. Conclusion: On the basis of the distribution and biokinetic data, the determined radiation dose for 18 F-FSPG was calculated to be 9.5 6 1.0 mSv at a patient dose of 300 MBq, which is of similar magnitude to that of 18 F-FDG (5.7 mSv). The effective dose can be reduced to 4.5 6 0.30 mSv (at 300 MBq), with a bladder-voiding interval of 0.75 h.