Purpose Gallium-68 (Ga-68)-labeled tracers for imaging expression of the prostate-specific membrane antigen (PSMA) such as the [⁶⁸Ga]Ga-PSMA-HBED-CC have already demonstrated high potential for the detection of recurrent prostate cancer. However, compared to Ga-68, a labeling with fluorine-18 (F-18) would offer advantages with respect to availability, production amount, and image resolution. [¹⁸F]DCFPyL is a promising F-18-labeled candidate for PSMA-positron emission tomography (PET) imaging that has been recently introduced. In the current study, we aimed to compare [⁶⁸Ga]Ga-PSMA-HBED-CC and [¹⁸F]DCFPyL for clinical use in biochemically relapsed prostate cancer. Procedures In 14 selected patients with PSA relapse of prostate cancer, [¹⁸F]DCFPyL PET/X-ray computed tomography (CT) was performed in addition to [⁶⁸Ga]Ga-PSMA-HBED-CC PET/CT. A systematic comparison was carried out between results obtained with both tracers with regard to the number of detected PSMA-positive lesions, the standardized uptake value (SUV)_max and the lesion to background ratios. Results All suspicious lesions identified by [⁶⁸Ga]Ga-PSMA-HBED-CC were also detected with [¹⁸F]DCFPyL. In three patients, additional lesions were observed using [¹⁸F]DCFPyL PET/CT. The mean SUV_max in the concordant [¹⁸F]DCFPyL PSMA-positive lesions was significantly higher as compared to [⁶⁸Ga]Ga-PSMA-HBED-CC (14.5 vs. 12.2, p = 0.028, n = 15). The mean tumor to background ratios (n = 15) were significantly higher for [¹⁸F]DCFPyL compared to [⁶⁸Ga]Ga-PSMA-HBED-CC using kidney, spleen, or parotid as reference organs (p = 0.006, p = 0.002, p = 0.008), but no significant differences were found using the liver (p = 0.167) or the mediastinum (p = 0.363) as reference organs. Conclusion [¹⁸F]DCFPyL PET/CT provided a high image quality and visualized small prostate lesions with excellent sensitivity. [¹⁸F]DCFPyL represents a highly promising alternative to [⁶⁸Ga]Ga-PSMA-HBED-CC for PSMA-PET/CT imaging in relapsed prostate cancer.

PURPOSE: Previous studies have shown that bone metastases are revealed by magnetic resonance imaging (MRI) or bone marrow scintigraphy several months before they are visible by conventional bone scintigraphy (BS). We present a new approach for detecting bone metastases in patients with breast cancer. We compared findings obtained with fluoride ion (F-18) and positron emission tomography (PET) with those obtained with conventional BS. PATIENTS AND METHODS: Thirty-four breast cancer patients were prospectively examined using F-18–PET and conventional BS. F-18–PET and BS were performed within 3 weeks of each other. Metastatic bone disease was previously known to be present in six patients and was suspected (bone pain or increasing levels of tumor markers, Ca²⁺, alkaline phosphatase) in 28 patients. Both imaging modalities were compared by patient-by-patient analysis and lesion-by-lesion analysis, using a five-point scale for receiver operating characteristic (ROC) curve analysis. A panel of reference methodswas used, including MRI (28 patients), planar x-ray (17 patients), and spiral computed tomography (four patients). RESULTS: With F-18–PET, 64 bone metastases were detected in 17 patients. Only 29 metastases were detected in 11 patients with BS. As a result of F-18–PET imaging, clinical management was changed in four patients (11.7%). For F-18–PET, the area under the ROC curve was 0.99 on a lesion basis (for BS, it was 0.74; P < .05) and 1.00 on a patient basis (for BS, it was 0.82; P < .05). CONCLUSION: F-18–PET demonstrates a very early bone reaction when small bone marrow metastases are present, allowing accurate detection of breast cancer bone metastases. This accurate detection has a significant effect on clinical management, compared with the effect on management brought about by detection with conventional BS.

The molecular mechanisms that control the balance between antiangiogenic and proangiogenic factors and initiate the angiogenic switch in tumors remain poorly defined. By combining chemical genetics with multimodal imaging, we have identified an autocrine feed-forward loop in tumor cells in which tumor-derived VEGF stimulates VEGF production via VEGFR2-dependent activation of mTOR, substantially amplifying the initial proangiogenic signal. Disruption of this feed-forward loop by chemical perturbation or knockdown of VEGFR2 in tumor cells dramatically inhibited production of VEGF in vitro and in vivo. This disruption was sufficient to prevent tumor growth in vivo. In patients with lung cancer, we found that this VEGF:VEGFR2 feed-forward loop was active, as the level of VEGF/VEGFR2 binding in tumor cells was highly correlated to tumor angiogenesis. We further demonstrated that inhibition of tumor cell VEGFR2 induces feedback activation of the IRS/MAPK signaling cascade. Most strikingly, combined pharmacological inhibition of VEGFR2 (ZD6474) and MEK (PD0325901) in tumor cells resulted in dramatic tumor shrinkage, whereas monotherapy only modestly slowed tumor growth. Thus, a tumor cell-autonomous VEGF:VEGFR2 feed-forward loop provides signal amplification required for the establishment of fully angiogenic tumors in lung cancer. Interrupting this feed-forward loop switches tumor cells from an angiogenic to a proliferative phenotype that sensitizes tumor cells to MAPK inhibition.

Several studies outlined the sensitivity of ⁶⁸Ga-labeled PET tracers against the prostate-specific membrane antigen (PSMA) for localization of relapsed prostate cancer in patients with renewed increase in the prostate-specific antigen (PSA), commonly referred to as biochemical recurrence. Labeling of PSMA tracers with ¹⁸F offers numerous advantages, including improved image resolution, longer half-life, and increased production yields. The aim of this study was to assess the PSA-stratified performance of the ¹⁸F-labeled PSMA tracer ¹⁸F-DCFPyL and the ⁶⁸Ga-labeled reference ⁶⁸Ga-PSMA-HBED-CC. Methods: We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols using ¹⁸F-DCFPyL (n = 62, 269.8 MBq, PET scan at 120 min after injection) or ⁶⁸Ga-PSMA-HBED-CC (n = 129, 158.9 MBq, 60 min after injection). We determined PSA-stratified sensitivity rates for both tracers and corrected our calculations for Gleason scores using iterative matched-pair analyses. As an orthogonal validation, we directly compared tracer distribution patterns in a separate cohort of 25 patients, sequentially examined with both tracers. Results: After prostatectomy (n = 106), the sensitivity of both tracers was significantly associated with absolute PSA levels (P = 4.3 × 10⁻³). Sensitivity increased abruptly, when PSA values exceeded 0.5 μg/L (P = 2.4 × 10⁻⁵). For a PSA less than 3.5 μg/L, most relapses were diagnosed at a still limited stage (P = 3.4 × 10⁻⁶). For a PSA of 0.5–3.5 μg/L, PSA-stratified sensitivity was 88% (15/17) for ¹⁸F-DCFPyL and 66% (23/35) for ⁶⁸Ga-PSMA-HBED-CC. This significant difference was preserved in the Gleason-matched-pair analysis. Outside of this range, sensitivity was comparably low (PSA < 0.5 μg/L) or high (PSA > 3.5 μg/L). After radiotherapy (n = 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of ¹⁸F-DCFPyL and ⁶⁸Ga-PSMA-HBED-CC were strongly comparable (P = 2.71 × 10⁻⁸). However, in 36% of the PSMA-positive patients we detected additional lesions on the ¹⁸F-DCFPyL scan (P = 3.7 × 10⁻²). Conclusion: Our data suggest that ¹⁸F-DCFPyL is noninferior to ⁶⁸Ga-PSMA-HBED-CC, while offering the advantages of ¹⁸F labeling. Our results indicate that imaging with ¹⁸F-DCFPyL may even exhibit improved sensitivity in localizing relapsed tumors after prostatectomy for moderately increased PSA levels. Although the standard acquisition protocols, used for ¹⁸F-DCFPyL and ⁶⁸Ga-PSMA-HBED-CC in this study, stipulate different activity doses and tracer uptake times after injection, our findings provide a promising rationale for validation of ¹⁸F-DCFPyL in future prospective trials.

We have determined the ability of positron emission tomography (PET) with the thymidine analogue 3′-deoxy-3′-[¹⁸F]fluorothymidine (FLT) to detect manifestation sites of malignant lymphoma, to assess proliferative activity, and to differentiate aggressive from indolent tumors. In this prospective study, FLT-PET was done additionally to routine staging procedures in 34 patients with malignant lymphoma. Sixty minutes after i.v. injection of ∼330 MBq FLT, emission and transmission scanning was done. Tracer uptake in lymphoma was evaluated semiquantitatively by calculation of standardized uptake values (SUV) and correlated to tumor grading and proliferation fraction as determined by Ki-67 immunohistochemistry. FLT-PET detected a total of 490 lesions compared with 420 lesions revealed by routine staging. In 11 patients with indolent lymphoma, mean FLT-SUV in biopsied lesions was 2.3 (range, 1.2-4.5). In 21 patients with aggressive lymphoma, a significantly higher FLT uptake was observed (mean FLT-SUV, 5.9; range, 3.2-9.2; P < 0.0001) and a cutoff value of SUV = 3 accurately discriminated between indolent and aggressive lymphoma. Linear regression analysis indicated significant correlation of FLT uptake in biopsied lesions and proliferation fraction (r = 0.84; P < 0.0001). In this clinical study, FLT-PET was suitable for imaging malignant lymphoma and noninvasive assessment of tumor grading. Due to specific imaging of proliferation, FLT may be a superior PET tracer for detection of malignant lymphoma in organs with high physiologic fluorodeoxyglucose uptake and early detection of progression to a more aggressive histology or potential transformation. (Cancer Res 2006; 66(22): 11055-61)