Radioiodinated benzimidazole derivatives as single photon emission computed tomography probes for imaging of β-amyloid plaques in Alzheimer's disease

Five iodinated 2-phenyl-1H-benzo[d]imidazole derivatives were synthesized and evaluated as potential probes for β-amyloid (Aβ) plaques. One of the compounds, 4-(6-iodo-1H-benzo[d]imidazol-2-yl)-N,N-dimethylaniline (12), showed excellent affinity for Aβ(1-42) aggregates (K(i) = 9.8 nM). Autoradiography with sections of postmortem Alzheimer's disease (AD) brain revealed that a radioiodinated probe [(125)I]12, labeled Aβ plaques selectively with low nonspecific binding. Biodistribution experiments with normal mice injected intravenously with [(125)I]12 showed high uptake [4.14 percent injected dose per gram (% ID/g) at 2 min] into and rapid clearance (0.15% ID/g at 60 min) from the brain, which may bring about a good signal-to-noise ratio and therefore achieve highly sensitive detection of Aβ plaques. In addition, [(125)I]12 labeled amyloid plaques in vivo in an AD transgenic model. The preliminary results strongly suggest that [(125)I]12 bears characteristics suitable for detecting amyloid plaques in vivo. When labeled with (123)I, it may be a useful SPECT imaging agent for Aβ plaques in the brain of living AD patients.     

Characterization of IMPY as a potential imaging agent for β-amyloid plaques in double transgenic PSAPP mice

Deposition of -amyloid (A) plaques in the brain is likely linked to the pathogenesis of Alzheimers disease (AD). Developing specific A aggregate-binding ligands as in vivo imaging agents may be useful for diagnosis and monitoring the progression of AD. We have prepared a thioflavin derivative, 6-iodo-2-(4-dimethylamino-)phenyl-imidazo[1,2-a]pyridine, IMPY, which is readily radiolabeled with ¹²⁵I/¹²³I for binding or single-photon emission computerized tomography (SPECT) imaging studies. Characterization of [¹²⁵I]IMPY binding to plaque-like structures was evaluated in double transgenic PSAPP mice. [¹²⁵I]IMPY labeled A plaques in transgenic mouse brain sections, and the labeling was consistent with fluorescent staining and A-specific antibody labeling. Significant amounts of A plaques present in the cortical, hippocampal, and entorhinal regions of the transgenic mouse brain were clearly detected with [¹²⁵I]IMPY via ex vivo autoradiography. In contrast, [¹²⁵I]IMPY showed little labeling in the age-matched control mouse brain. Tissue homogenate binding further corroborated the A plaque-specific distribution in various brain regions of transgenic mouse, and correlated well with the known density of A deposition. Using a tissue dissection technique, [¹²⁵I]IMPY showed a moderate increase in the cortical region of transgenic mice as compared to the age-matched controls. In vitro blocking of [¹²⁵I]IMPY by carrier observed via autoradiography in mouse brain sections was not replicated by an in vivo blocking experiment in living TT mouse brain. The failure was most likely due to a significant carrier effect, which slows down the tracer in vivo metabolism, leading to an increased brain uptake. Taken together, these data indicate that [¹²³I]IMPY is a potentially useful SPECT imaging agent for in vivo labeling of A plaques in the living brain.     

Flare phenomenon in positron emission tomography in a case of breast cancer—a pitfall of positron emission tomography imaging interpretation

We present an unusual case of breast cancer with increased FDG uptake 4 months after chemotherapy. A PET-CT scan displayed results that mimicked multiple lymph node metastases in the right axilla, the mediastinum, and the bilateral pulmonary hilar regions. However, the increased FDG uptake disappeared 17 months later without any additional medical treatment, suggesting the occurrence of flare phenomenon.     

Radiopharmaceuticals for positron emission tomography investigations of Alzheimer’s disease

Alzheimer’s disease (AD) is a common degenerative neurological disease that is an increasing medical, economical, and social problem. There is evidence that a long “asymptomatic” phase of the disease exists where functional changes in the brain are present, but structural imaging for instance with magnetic resonance imaging remains normal. Positron emission tomography (PET) is one of the tools by which it is possible to explore changes in cerebral blood flow and metabolism and the functioning of different neurotransmitter systems. More recently, investigation of protein aggregations such as amyloid deposits or neurofibrillary tangles containing tau-protein has become possible. The purpose of this paper is to review the current knowledge on various ¹⁸F- and ¹¹C-labelled PET tracers that could be used to study the pathophysiology of AD, to be used in the early or differential diagnosis or to be used in development of treatment and in monitoring of treatment effects.     

Evaluation of Wegener’s granulomatosis using 18F-fluorodeoxyglucose positron emission tomography/computed tomography

Objective

Wegener’s granulomatosis (WG) is a relatively rare disease characterized by granulomatous necrotizing vasculitis that primarily involves small- and medium-sized vessels. Systemic findings observed on ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) have not been well reported. The purpose of this study was to evaluate the FDG PET/CT imaging in the diagnosis and follow-up of patients with WG.

Materials and methods

Thirteen FDG PET/CT images obtained for 8 patients (2 men and 6 women) with WG were retrospectively analyzed. Of these, 6 were performed for diagnosis, 2 for restaging and follow-up, and 5 for assessment of treatment efficacy. Maximum standardized uptake values (max SUVs) and visual analyses were used to interpret the FDG PET/CT images. In addition, nonenhanced CT findings obtained during FDG PET/CT were described.

Results

WG lesions of the upper respiratory tract and lung were more clearly detected by FDG PET/CT fusion imaging than by nonenhanced CT alone, and all of the active lesions showed decreased FDG uptake after treatment. In addition, FDG PET/CT can provide complementary information to indicate biopsy site based on FDG uptakes.

Conclusions

FDG PET/CT is a feasible modality for evaluating lesion activities, therapeutic monitoring, and follow-up of WG. Furthermore, biopsy sites of WG lesions may be determined by FDG PET/CT.     

18F-Labeled benzylideneaniline derivatives as new ligands for β-amyloid plaque imaging in Alzheimer's disease

IntroductionNoninvasive early detection of β-amyloid (Aβ) plaques might be useful for the treatment of patients with Alzheimer's disease (AD). We herein describe the synthesis of ¹⁸F-labeled benzylideneaniline derivatives using a novel labeling approach for imaging Aβ plaques in AD patients.MethodsBenzylidenaniline derivatives were synthesized by reacting fluorobenzaldehyde and corresponding aniline derivatives. Fluorobenzaldehyde was labeled with ¹⁸F by incubating [¹⁸F]fluoride with N,N,N-trimethylbenzaldehyde in the presence of tetrabutylammonium bicarbonate. In vitro binding assay, stability test and biodistribution study were performed.ResultsThese compounds were stable at alkaline pH (pH >9); however, they were hydrolyzed rapidly at physiological pH (pH ～7.4). The K_i values of amine-containing benzylideneaniline derivatives for Aβ_1–40 and Aβ_1–42 aggregates were 26–78 nM. These ¹⁸F-labeled benzylideneaniline derivatives showed high brain uptake and rapid clearance after intravenous administration in normal mice (1.8–3.1%ID/g at 2 min and 0.1–1.2%ID/g at 30 min). The low level of bone activity at 30 min indicated that these ¹⁸F-labeled benzylideneanilines are not prone to defluorination. Furthermore, the compounds have suitable lipophilicity — a property required to penetrate the blood–brain barrier.ConclusionThese results showed that the instability of these compounds could cause a higher early phase/late phase ratio due to rapid clearance in the normal brain. The findings from this study suggest that these ¹⁸F-labeled benzylideneaniline derivatives are feasible for the imaging of Aβ plaques.     

GMP-compliant automated synthesis of [18F]AV-45 (Florbetapir F 18) for imaging β-amyloid plaques in human brain

We report herein the Good Manufacturing Practice (GMP)-compliant automated synthesis of ¹⁸F-labeled styrylpyridine, AV-45 (Florbetapir), a novel tracer for positron emission tomography (PET) imaging of β-amyloid (Aβ) plaques in the brain of Alzheimer’s disease patients. [¹⁸F]AV-45 was prepared in 105 min using a tosylate precursor with Sumitomo modules for radiosynthesis under GMP-compliant conditions. The overall yield was 25.4±7.7% with a final radiochemical purity of 95.3±2.2% (n=19). The specific activity of [¹⁸F]AV-45 reached as high as 470±135 TBq/mmol (n=19). The present studies show that [¹⁸F]AV-45 can be manufactured under GMP-compliant conditions and could be widely available for routine clinical use.     

Synthesis and biological evaluation of two agents for imaging estrogen receptor β by positron emission tomography: challenges in PET imaging of a low abundance target

IntroductionIndependent measurement of the levels of both the estrogen receptors, ERα and ERβ, in breast cancer could improve prediction of benefit from endocrine therapies. While ERα levels can be measured by positron emission tomography (PET) using 16α-[¹⁸F]fluoroestradiol (FES), no effective agent for imaging ERβ by PET has yet been reported.MethodsWe have prepared the fluorine-18 labeled form of 8β-(2-fluoroethyl)estradiol (8BFEE₂), an analog of an ERβ-selective steroidal estrogen, 8β-vinylestradiol; efficient incorporation of fluorine-18 was achieved, but required very vigorous conditions. We have examined the biodistribution of this compound, as well as of Br-041, an analog of a known non-steroidal ERβ-selective ligand (ERB-041), labeled with bromine-76. Studies were done in immature female rodents, with various pharmacological and endocrine perturbations to assess ERβ selectivity of uptake.ResultsLittle evidence of ERβ-mediated uptake was observed with either [¹⁸F]8BFEE₂ or [⁷⁶Br]Br-041. Attempts to increase the ERβ content of target tissues were not effective and failed to improve biodistribution selectivity.ConclusionsBecause on an absolute basis level, ERβ levels are low in all target tissues, these studies have highlighted the need to develop improved in vivo models for evaluating ERβ-selective radiopharmaceuticals for use in PET imaging. Genetically engineered breast cancer cells that are being developed to express either ERα or ERβ in a regulated manner, grown as xenografts in immune-compromised mice, could prove useful for future studies to develop ER subtype-selective radiopharmaceuticals.     

FDG positron emission tomography/computed tomography studies of Wilms’ tumor

Purpose  

The purpose of this analysis was to evaluate the utility of FDG PET/CT scanning in patients with Wilms’ tumors.     

Evaluation of [11C]GB67, a novel radioligand for imaging myocardial α1-adrenoceptors with positron emission tomography

Dysfunction of the sympathetic nervous system underlies a number of myocardial disorders. Positron emission tomography (PET) offers a way of assessing receptor function non-invasively in humans, but there are no PET radioligands for assessing myocardial α-adrenoceptors. GB67, a structural and pharmacological analogue of the α₁-adrenoceptor antagonist prazosin, was labelled with positron-emitting carbon-11 (t _1/2=20.4 min) by ¹¹C-methylation of N-desmethylamido-GB67 (GB99). [¹¹C]GB67 was injected intravenously into conscious rats. Serial arterial blood samples were taken. Rats were killed and tissues removed to determine radioactivity. The percentages of unchanged [¹¹C]GB67 and its radioactive metabolites in plasma and tissues were assessed by HPLC. Plasma clearance of radioactivity was rapid. Myocardial uptake was maximal at 1–2 min and decreased slowly during 60 min. Predosing with adrenoceptor antagonists demonstrated selectivity for myocardial α₁-adrenoceptors. GB67 and prazosin blocked uptake of radioactivity; the non-selective antagonist, phentolamine, partially blocked uptake; the α₂-adrenoceptor antagonist, RX 821002, only blocked uptake at high dose and the β-adrenoceptor antagonist, CGP 12177, had no effect. Additionally, injection of prazosin at 20 min after radioligand displaced radioactivity. In vivo competition curves obtained by injecting [¹¹C]GB67 with varying amounts of either unlabelled GB67 or its precursor GB99 were fitted to a competitive binding model to provide estimates of the maximum number of binding sites (B _max) and half saturation doses (K) for myocardium. Assuming a tissue protein content of 10%, the values of B _max [∼13 pmol·(g tissue)^–1] were similar to those [50–170 fmol·(mg protein)^–1] reported for myocardial α₁-adrenoceptors assessed in vitro. Both GB67 and its precursor GB99 had high affinity for α₁-adrenoceptors [K _GB67=1.5 nmol·(kg body weight)^–1, K _GB99=4.8 nmol· (kg body weight)^–1]. HPLC demonstrated four radioactive metabolites in plasma. [¹¹C]GB67 was 80% of the radioactivity at 5 min and 50% at 45 min. No radioactive metabolites were detected in myocardium up to 60 min after injection. [¹¹C]GB67 was assessed in two male human volunteers. PET demonstrated high myocardial uptake. The profile of radioactive metabolites in plasma was comparable to that in the rat, although metabolism was slower in humans. Thus, [¹¹C]GB67 is a promising radioligand for assessing α₁-adrenoceptors in human myocardium with PET. Received 7 May and in revised form 9 August 1999     

Tumor lesion detection: when is integrated positron emission tomography/computed tomography more accurate than side-by-side interpretation of positron emission tomography and computed tomography?

OBJECTIVES: To determine if there is added value to oncology studies performed with a dedicated in-line positron emission tomography (PET)/computed tomography (CT) scanner as compared with PET read side by side with diagnostic CT (DCT). METHODS: Forty-one consecutive oncology patients referred for PET/CT who had contemporary DCT scans for review were enrolled. Body regions assessed on a DCT scan were assessed on PET/CT and by side-by-side reading of PET and DCT (SBS PET/DCT). Lesions identified on DCT, the CT portion of PET/CT, SBS PET/DCT, and the reading of fused PET/CT images were scored as benign or malignant. The PET portion of the PET/CT study was read by 2 teams: the first read the SBS PET/DCT scan and the other read the complete fused PET/CT scan. For discordant lesions, the final diagnosis was determined by pathologic findings (n = 6) or imaging follow-up (n = 21). RESULTS: Twenty-seven (16.1%) of the 168 lesions were discordant when comparing analysis of fused PET/CT and SBS PET/DCT. Sixteen (9.5%) were fundamentally discordant, and 11(6.6%) were discordant in degree of confidence. For all discordant lesions only, the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for PET/CT were 100%, 33%, 100%, 94%, and 78%, respectively, and for SBS PET/DCT, they were 38%, 50%, 19%, 73%, and 30%, respectively (P < 0.001 for sensitivity, P = not specific for specificity). The 2 main causes for misclassification on SBS PET/DCT were incorrect localization (n = 12) and changes occurring in the time gap between DCT and PET/CT (n = 4). CONCLUSIONS: In-line PET/CT offers better lesion localization in comparison to the visual fusion of PET and CT, especially for small lymph nodes, lesions adjacent to mobile organs, or lesions adjacent to the chest or abdominal wall.     

Evaluation of [O-methyl-11C]RS-15385-197 as a positron emission tomography radioligand for central α2-adrenoceptors

Carbon-11 labelled RS-15385-197 and its ethylsulphonyl analogue, RS-79948-197, were evaluated in rats as potential radioligands to image central α₂-adrenoceptors in vivo. The biodistributions of both compounds were comparable with that obtained in an earlier study using tritiated RS-79948-197 and were consistent with the known localisation of α₂-adrenoceptors. The maximal signals (total to non-specific binding) were, however, reduced, in the order [¹¹C]RS-79948-197 < [¹¹C]RS-15385-197 < [³H]RS-79948-197, primarily due to the difference in radiolabel position (O-methyl for carbon-11 compared with S-ethyl for tritium). This resulted in the in-growth of radiolabelled metabolites in plasma, which, in turn, contributed to the non-specific component of brain radioactivity. Nonetheless, the signal ratio of ∼5 for a receptor-dense tissue compared with the receptor-sparse cerebellum, at 90–120 min after radioligand injection, encouraged the development of [O-methyl-¹¹C]RS-15385-197 for human positron emission tomography (PET). Unfortunately, in two human PET scans (each of 90 min), brain extraction of the radioligand was minimal, with volumes of distribution more than an order of magnitude lower than that measured in rats. Following intravenous injection, radioactivity was retained in plasma and metabolism of the radiolabelled compound was very low. Retrospective measurements of in vitro plasma protein binding and in vivo brain uptake index (BUI) in rats demonstrated a higher protein binding of the radioligand in human compared with rat plasma and a lower BUI in the presence of human plasma. It is feasible that a higher affinity of RS-15385-197 for human plasma protein compared with receptor limited the transport of the radioligand. Although one of the PET scans showed a slight heterogeneity in biodistribution of radioactivity which was consistent with the known localisation of α₂-adrenoceptors in human brain, it was concluded that [O-methyl-¹¹C]RS-15385-197 showed little promise for routine quantification of α₂-adrenoceptors in man. Received 26 October 1999 and in revised form 21 January 2000     

Is hybridic positron emission tomography/computerized tomography the only option? The future of nuclear medicine and molecular imaging

As we all know, Nuclear Medicine is the medical science using nuclear radiation for diagnosis, treatment and research. Nuclear Medicine, in contrast to Radiology, makes use of unsealed sources of radiation. Nuclear Medicine a few years ago has partly offered Nuclear Cardiology, the most lucrative of all Nuclear Medicine "children" at that time, to Cardiology. Radiology, has succeeded in being recognized by the European Union Authorities as Clinical Radiology. The word "clinical" offers greater independence to Clinical Radiology and makes it difficult for such a specialty to relinquish any of its equipment i.e. the diagnostic CT scan or the newly developed fast angiography CT, to other specialties. Contrary to Clinical Radiology, Nuclear Medicine being a laboratory specialty in most countries seems to have no right to deny offering, after some period of "proper certified education", its PET camera to Clinical Radiologists. Nuclear Medicine by virtue of its unique diagnostic techniques and treatments, is and should be recognized as a "Clinical Specialty" The interference of other specialties in the fields of Nuclear Medicine is also indicated by the fact that in vitro techniques of Nuclear Medicine are often used by Endocrinologists and Oncologists in their own laboratories. Also in some hospitals the Director of the Radiology Department acts as the Director of Nuclear Medicine Laboratory. Finally at present, Radiologists wish after "proper certified education", to be on equal terms in charge of the new hybridic equipment, the PET/CT scanner. If that is followed to happen, Nuclear Medicine will be in a difficult position losing at least part of PET and consequently should ask for help from its "Overlords and Protectors" i.e. the National and the European Societies of Nuclear Medicine and the Society of Nuclear Medicine of the United States of America. Radiology as a specialty participating om equal terms with the PET camera will then include the study of: a) "open sources of radiation" b) nuclear radiation and c) molecular nuclear medicine. The "European Journal of Nuclear Medicine and Molecular Imaging" shall have to erase the three last words of its title and be renamed. As Professor Abass Alavi et al (2007), have mentioned: "Is PET/CT the only option?" In favor of PET/CT are the following: Attenuation correction (AC) and better anatomical localization of lesions visualized with PET. Also PET/CT can be used as a diagnostic CT scanner (dCT). Against using the PET/CT scanners are the following arguments: a) This equipment is not necessary because we can always ask the Radiologists for a dCT scan. Many patients have already done a dCT scan at the time they are referred for a PET scan to the Nuclear Medicine Department. b) The absolute clinical indications for PET/CT with the use of a contrast agent, are under investigation. c) Although there is at present a list of indications suggested for the PET/CT scanner, there are studies disputing some of these indications, as for example in metastatic colon cancer where a high diagnostic accuracy for PET study alone, has been reported. d) The option of AC performed by the PET/CT scanner has also been questioned. Artifacts may be up to 84%. e) The PET/CT is expensive, time consuming, space occupying, and needs additional medical and technical personnel. f) Not to mention the extra radiation dose to the patients. g) Shall we inform those young medical students who wish to become nuclear medicine physicians, to hold their decision till the content of future Nuclear Medicine is clarified? We may suggest that: Our specialty could be renamed as: "Clinical Nuclear Medicine" and include additional "proper certified education" on the PET/CT equipment. The PET/CT scanner should remain in the Nuclear Medicine Department where Radiologists could act as advisors.     

Biological evaluation of 3-[18F]fluoro-α-methyl-d-tyrosine (d-[18F]FAMT) as a novel amino acid tracer for positron emission tomography

Objective

3-[¹⁸F]Fluoro-α-methyl-l-tyrosine (l-[¹⁸F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. Because d-amino acids are not well distributed in non-target organs and are rapidly excreted in urine, the d-isomer of [¹⁸F]FAMT could allow clear PET imaging of tumors early after administration. In this study, we prepared 3-[¹⁸F]fluoro-α-methyl-d-tyrosine (d-[¹⁸F]FAMT) and evaluated its usefulness.

Methods

d-[¹⁸F]FAMT was synthesized according to the method for preparation of l-[¹⁸F]FAMT. The in vitro and in vivo stability of [¹⁸F]FAMT were evaluated by high-performance liquid chromatography. Cellular uptake of [¹⁸F]FAMT was evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in LS180 tumor-bearing mice, and the tumors were imaged using a small-animal PET scanner.

Results

The radiolabeling yield of d-[¹⁸F]FAMT was approximately 10 %, similar to that of l-[¹⁸F]FAMT. Over 95 % of d-[¹⁸F]FAMT remained intact in mice until 60 min after administration. d-[¹⁸F]FAMT was gradually taken up by the LS180 cells. Tumor uptake of d-[¹⁸F]FAMT was competitively inhibited by pretreatment with α-methyl-l-tyrosine, a selective substrate for the system l-amino acid transporter 1 (LAT1), suggesting the involvement of LAT1 in tumor uptake of d-[¹⁸F]FAMT. In biodistribution studies, d-[¹⁸F]FAMT showed rapid clearance from the blood, marked accumulation and retention in the tumor, and lower accumulation in non-target organs, especially kidney and pancreas, compared to l-[¹⁸F]FAMT. The amount of d-[¹⁸F]FAMT in the tumor was also reduced, and tumor-to-blood ratio and tumor-to-muscle ratio of d-[¹⁸F]FAMT were similar to those of l-[¹⁸F]FAMT at every time point. PET imaging with d-[¹⁸F]FAMT did not provide a clear image of the tumor early after administration. However, d-[¹⁸F]FAMT provided higher tumor-to-background contrast than l-[¹⁸F]FAMT.

Conclusions

d-[¹⁸F]FAMT showed rapid blood clearance, low accumulation in non-target organs, and tumor-selective imaging compared with l-[¹⁸F]FAMT. Thus, d-[¹⁸F]FAMT could potentially serve as a novel PET tracer for imaging malignant tumors.     

Does positron emission tomography data acquisition impact simultaneous diffusion-weighted imaging in a whole-body PET/MRI system?

Objectives

The purpose of this study was to test whether the acquisition of positron emission tomography (PET) does interfere with simultaneous diffusion weighted imaging (DWI) in an integrated whole-body PET/MRI system.

Material and methods

Fourteen consecutive oncological patients (9 men, 5 women; age 54 ± 13 years ([mean ± standard deviation]) scheduled for routine [¹⁸F]-FDG PET/CT were prospectively enrolled. For DWI, an echo planar imaging (EPI) sequence (b = 0–500–1000 s/mm²) was acquired twice on an integrated whole-body 3 T PET/MRI system in each patient; first with simultaneous PET acquisition and a second time with the PET component switched off. The apparent diffusion coefficient (ADC) and the signal-to-noise ratio at b = 1000 s/mm² (SNR) of the myocardium, paraspinal muscle, liver, spleen, renal cortex and tumor tissue (if present) were measured. In addition, the coefficient of variation (CV) of ADC values was calculated. Student's t-test for paired samples was performed to test for differences of the mean ADC, ADC CV and SNR between DWI with and without simultaneous PET acquisition.

Results

There were no significant differences of the ADC [(mean ± standard deviation)] between the DWI acquisitions with and without simultaneous PET acquisition for the myocardium (2572 ± 441 × 10⁻⁶ mm²/s and 2586 ± 376 × 10⁻⁶ mm²/s, respectively) (P = 0.817), paraspinal muscle (1279 ± 254 × 10⁻⁶ mm²/s vs. 1219 ± 181 × 10⁻⁶ mm²/s) (P = 0.318), liver (1245 ± 158 × 10⁻⁶ mm²/s vs. 1254 ± 171 × 10⁻⁶ mm²/s) (P = 0.848), spleen (980 ± 122 × 10⁻⁶ mm²/s vs. 1000 ± 187 × 10⁻⁶ mm²/s) (P = 0.676) and renal cortex (1951 ± 226 × 10⁻⁶ mm²/s vs. 1930 ± 273 × 10⁻⁶ mm²/s) (P = 0.730). Mean ADC of lymph node metastases (n = 6) did not differ between with PET acquisition (853 ± 174 × 10⁻⁶ mm²/s) and without simultaneous PET (865 ± 170 × 10⁻⁶ mm²/s) (P = 0.675). There were no significant differences between the CV of ADC values or the SNR values measured in DWI datasets that were acquired with or without simultaneous PET for any evaluated organ site.

Conclusion

The simultaneous acquisition of DWI and PET on an integrated PET/MRI system does not impact ADC quantification of normal and tumor tissue and does not alter SNR. This knowledge provides a basis for the use of simultaneous multiparametric PET/MRI comprising DWI in diagnostic imaging and quantitative tumor therapy monitoring using repeated ADC measurements.     

Fluorine-18 labeling and biodistribution studies on peroxisome proliferator-activated receptor-γ ligands: potential positron emission tomography imaging agents

IntroductionPeroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid metabolism; it controls the differentiation of preadipocytes and is also found at high levels in small metastatic tumors. In this report, we describe the radiochemical synthesis and evaluation of two ¹⁸F-labeled analogs of the potent and selective PPARγ agonist farglitazar.Materials and methodsThe isomeric aromatic fluorine-substituted target compounds [(2S)-(2-benzoylphenylamino)-3-(4-(2-[2-(4-[¹⁸F]fluorophenyl)-5-methyloxazol-4-yl]ethoxy)-phenyl)propionic acid ([¹⁸F]-1) and (2S)-[2-(4-fluorobenzoyl)phenylamino]-3-(4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-phenyl)propionic acid ([¹⁸F]-2)] were prepared in fluorine-18-labeled form, respectively, by radiofluorination of an iodonium salt precursor or by Ullmann-type condensation with 2-iodo-4′-[¹⁸F]fluorobenzophenone after nucleophilic aromatic substitution with [¹⁸F]fluoride ion. Each compound was obtained in high specific activity and good radiochemical yield.Results and Discussion¹⁸F-1 and ¹⁸F-2 have high and selective PPARγ binding affinities comparable to that of the parent molecule farglitazar, and they were found to have good metabolic stability. Tissue biodistribution studies of ¹⁸F-1 and ¹⁸F-2 were conducted, but PPARγ-mediated uptake of both agents was minimal.ConclusionThis study completes our first look at an important class of PPARγ ligands as potential positron emission tomography (PET) imaging agents for breast cancer and vascular disease. Although ¹⁸F-1 and ¹⁸F-2 have high affinities for PPARγ and good metabolic stability, their poor target-tissue distribution properties, which likely reflect their high lipophilicity combined with the low titer of PPARγ in target tissues, indicate that they have limited potential as PPARγ PET imaging agents.