A Discordant Pattern of Uptake on 68 Ga-PSMA PET/CT Versus 18 F-Fluciclovine PET/CT in Radiation-Induced Hepatitis : Implications for Early Postradiotherapy Imaging-Based Response Assessment.

ABSTRACT: A 62-year-old woman with right-sided invasive lobular breast carcinoma completed external beam radiotherapy 6 weeks before undergoing a 68 Ga-PSMA PET/CT and 18 F-fluciclovine PET/CT scan as part of an ongoing clinical trial (NCT04750473) assessing the performance of these molecular imaging modalities in invasive lobular breast carcinoma. The 68 Ga-PSMA PET/CT demonstrated a band-like area of increased radiotracer uptake in the dome of the right lobe of the liver anteriorly, whereas 18 F-fluciclovine PET/CT done a day later revealed photopenia in the corresponding area of the liver. The external beam radiotherapy plan confirmed that the radiotherapy field overlaid the region of the hepatic discordant radiotracer uptake on the PET/CT scans.

A Tale of 3 Tracers: Contrasting Uptake Patterns of 18F-Fluciclovine, 68Ga-PSMA, and 18F-FDG in the Uterus and Adnexa.

ABSTRACT: A 41-year-old woman with invasive lobular carcinoma of the breast underwent sequential 68Ga-PSMA-11 PET/CT and 18F-fluciclovine PET/CT as part of an ongoing clinical trial (NCT04750473). 68Ga-PSMA PET/CT showed increased radiotracer uptake in the uterine endometrium and left adnexa. 18F-fluciclovine PET/CT showed increased radiotracer uptake in a leiomyomatous uterus. A clinical 18F-FDG PET/CT demonstrated radiotracer uptake in the endometrium and a circumferential area of uptake in the left adnexa, a pattern more similar to the 68Ga-PSMA uptake pattern. This case highlights the discordance in the uptake pattern of 2 radiotracers approved for prostate cancer imaging but increasingly used in non-prostate malignancies imaging.

An improved synthesis of [11C]MENET via Suzuki coupling with [11C]methyl iodide.

[(11) C]MENET, a promising norepinephrine transporter imaging agent, was prepared by Suzuki cross coupling of 1 mg N-t-Boc pinacolborate precursor with [(11) C]CH3 I in DMF using palladium complex generated in situ from Pd2 (dba)3 and (o-CH3 C6 H4 )3 P together with K2 CO3 as the co-catalyst, followed by deprotection with trifluoroacetic acid. This improved radiolabeling method provided [(11) C]MENET in high radiochemical yield at end of synthesis (EOS, 51 ± 3%, decay-corrected from end of (11) CH3 I synthesis, n = 6), moderate specific activity (1.5-1.9 Ci/µmol at EOS), and high radiochemical (>98%) and chemical purity (>98%) in a synthesis time of 60 ± 5 min from the end of bombardment.

Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration.

CONTEXT: Inflammatory cytokines or cytokine inducers can alter basal ganglia activity, including reducing responsiveness to rewarding stimuli that may be mediated by cytokine effects on dopamine function. OBJECTIVES: To determine whether long-term administration of the inflammatory cytokine interferon alfa reduces the basal ganglia response to reward and whether such changes are associated with decreased presynaptic striatal dopamine function and altered behavior. DESIGN: Cross-sectional and longitudinal studies. SETTING: Outpatient research unit and neuroimaging facilities at Emory University, Atlanta, Georgia. PATIENTS: Medically stable adults with chronic hepatitis C virus (HCV) infection eligible for interferon alfa treatment. MAIN OUTCOME MEASURES: Neural activity in the ventral striatum during a hedonic reward task as measured by functional magnetic resonance imaging, uptake and turnover of radiolabeled fluorodopa F 18 (18F-dopa) in caudate and putamen using positron emission tomography, and interferon alfa-induced depression, anhedonia, fatigue, and neurotoxicity. RESULTS: Patients with HCV receiving interferon alfa for 4 to 6 weeks (n = 14) exhibited significantly reduced bilateral activation of the ventral striatum in the win vs lose condition of a gambling task compared with patients with HCV awaiting interferon alfa treatment (n = 14). Reduced activation of the ventral striatum was, in turn, significantly correlated with anhedonia, depression, and fatigue. In a separate longitudinal study, patients with HCV treated with interferon alfa for 4 to 6 weeks (n = 12) exhibited significantly increased 18F-dopa uptake and decreased 18F-dopa turnover in caudate and putamen and in the same ventral striatal regions identified in the functional magnetic resonance imaging study. Baseline and percentage change in 18F-dopa uptake and turnover were correlated with behavioral alterations, including depression, fatigue, and neurotoxicity, during interferon alfa administration. CONCLUSIONS: These data replicate and extend findings that inflammatory stimuli, including inflammatory cytokines, such as interferon alfa, alter basal ganglia activity and behavior in association with significant changes in presynaptic striatal dopamine function consistent with decreased dopamine synthesis or release.

Pilot evaluation of anti-1-amino-2-[18F] fluorocyclopentane-1-carboxylic acid (anti-2-[18F] FACPC) PET-CT in recurrent prostate carcinoma.

PURPOSE: Anti-1-amino-2-[(18)F]fluorocyclopentane-1-carboxylic acid (anti-2-[(18)F]FACPC) is an unnatural alicyclic amino acid radiotracer with high uptake in the DU-145 prostate cancer cell line in vitro. Our goal was to determine if anti-2-[(18)F]FACPC is useful in the detection of prostate carcinoma. PROCEDURES: Five patients with elevated PSA (1.1-20.5 ng/mL) after curative therapy for prostate carcinoma underwent 60 min dynamic positron emission tomography (PET) of the pelvis after IV injection of 193-340 MBq of anti-2-[(18)F]FACPC. Uptake was compared against PET scans in the same patients with the leucine analog, anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid (anti-[(18)F]FACBC), at similar time points and validated via pathology, clinical, and imaging follow-up. RESULTS: At 5 min, average (±SD) SUVmax of malignant lesions is 4.1(±1.3) for anti-2-[(18)F] FACPC and 4.3(±1.1) for anti-[(18)F]FACBC. Yet, blood pool activity at 5 min is significantly higher for anti-2-[(18)F]FACPC with average (±SD) lesion/blood pool SUVmax/SUVmean ratio of 1.4 (±0.5) vs. 3.0 (±0.9) for anti-[(18)F]FACBC. At 20 min, average (±SD) SUVmax of malignant lesions is 2.6 (±1.0) for anti-2-[(18)F]FACPC and 3.4 (±0.8) for anti-[(18)F]FACBC. Yet, bladder activity at 20 min is significantly more intense for anti-2-[(18)F] FACPC with average (±SD) lesion/bladder SUVmax/SUVmean ratio of 0.3 (±0.8) vs. 2.3 (±1.4) for anti-[(18)F]FACBC. CONCLUSIONS: While prostate bed lesions are visible on early imaging with anti-2-[(18)F]FACPC, there is high blood pool activity obscuring nodes. As blood pool fades, nodal uptake decreases and high bladder activity then obscures pelvic structures. Compared with anti-[(18)F]FACBC, imaging characteristics for anti-2-[(18)F]FACPC are unfavorable for pelvic recurrent prostate carcinoma detection.

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression.

PURPOSE: L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. METHODS: LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid (anti-[(18)F]FACBC) PET was assessed for its diagnostic biomarker potential. RESULTS: Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high-grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced-stage breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-amino-bicyclo[2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, anti-[(18)F]FACBC, has been demonstrated to be an excellent PET tracer for the non-invasive imaging of malignant breast cancer using an orthotopic animal model. CONCLUSIONS: The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. Anti-[(18)F]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.

Semi-automated preparation of the dopamine transporter ligand [(18)F]FECNT for human PET imaging studies.

The fluorine-18 labeled dopamine transport (DAT) ligand 2 beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (FECNT) has shown promising properties as an in vivo DAT imaging agent in human and monkey PET studies. A semi-automated synthesis has been developed to reliably produce [(18)F]FECNT in a 16% decay corrected yield. This method utilizes a new [(18)F]fluoralkylating agent and provides high purity [(18)F]FECNT in a formulation suitable for human use.

Neutron measurements in the vicinity of a self-shielded PET cyclotron.

The radionuclides used in positron emission tomography (PET) are short-lived and generally must be produced on site using a cyclotron. A common end product of the nuclear reactions used to produce the PET radionuclides is neutron radiation. These neutrons could potentially contribute to the annual effective dose received by hospital personnel. A Bonner sphere spectrometer was used to measure neutron energy spectra at three locations near a self-shielded PET cyclotron. This cyclotron accelerates protons to 11 MeV. The neutron measurements reported were made during the production of 18F via the 18O(p,n)18F reaction (Q = -2.4 MeV). Neutron spectra were obtained with the BUMS unfolding code and converted to dose equivalent rates.

Improved synthesis of anti-[18F]FACBC: improved preparation of labeling precursor and automated radiosynthesis.

The non-natural amino acid anti-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid (FACBC) has shown promise for tumor imaging with positron emission tomography. An improved synthesis of the precursor of anti-[18F]FACBC has been devised which demonstrates high stereoselectivity and suitability for large-scale preparations. An automated radiosynthesis has been developed which provides anti-[18F]FACBC in 24% decay-corrected yield. Additionally, the major non-radioactive species present in doses of anti-[18F]FACBC has been identified as anti-1-amino-3-hydroxycyclobutane-1-carboxylic acid. Together, these results are important steps towards the routine production of anti-[18F]FACBC for human use.