Radiosynthesis and biological evaluation of 18F-labeled 4-anilinoquinazoline derivative (18F-FEA-Erlotinib) as a potential EGFR PET agent

Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1N-(3-(1-(2-¹⁸F-fluoroethyl)-1H-1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (¹⁸F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. ¹⁸F-FEA-Erlotinib was achieved within 50 min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50 GBq/μmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of ¹⁸F-FEA-Erlotinib after incubated in PBS and FBS for 2 h. Cellular uptake and efflux experiment results indicated the specific binding of ¹⁸F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that ¹⁸F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of ¹⁸F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using ¹⁸F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients.     

Synthesis and evaluation of 18F-hexafluorophosphate as a novel PET probe for imaging of sodium/iodide symporter in a murine C6-glioma tumor model

Noninvasive imaging of iodide uptake via the sodium/iodide symporter (NIS) has received great interest for evaluation of thyroid cancer and reporter imaging of NIS-expressing viral therapies. In this study, we investigate ¹⁸F-labeled hexafluorophosphate (HFP or PF₆^?) as a high-affinity iodide analog for NIS imaging. ¹⁸F-HFP was synthesized by radiofluorination of phosphorus pentafluoride·N-methylpyrrolidine complex and evaluated in human NIS (hNIS)-expressing C6 glioma cells and a C6 glioma xenograft mouse model. ¹⁸F-HFP was obtained in radiochemical yield of 10?±?5%, radiochemical purity of >96% and specific radioactivity of 604?±?18?MBq/µmol. Specific uptake of ¹⁸F-HFP and high affinity of ¹⁹F-HFP were observed in hNIS+ C6-glioma cells. PET imaging showed robust uptake of ¹⁸F-HFP in NIS-expressing tissues (thyroid, stomach, and hNIS+ C6 glioma xenografts), and the uptake of ¹⁸F-HFP was blocked by NaClO₄ pretreatment. Specific accumulation in hNIS-expressing xenograft (hNIS+) was observed relative to isogenic control tumor (hNIS?). Clearance of ¹⁸F-HFP was predominantly through renal excretion. The biodistribution showed consistent results with PET imaging. Minimal bone uptake was observed over 2?h period post-injection, indicating excellent in vivo stability of ¹⁸F-HFP. Although improvement in specific radioactivity is desirable, the results indicate that ¹⁸F-HFP is a promising candidate radiotracer for further evaluation for NIS imaging.     

N-[18F]-Fluoroacetylcrizotinib: A potentially potent and selective PET tracer for molecular imaging of non-small cell lung cancer

N-[¹⁸F]fluoroacetylcrizotinib, a fluorine-18 labeled derivative of the first FDA approved tyrosine kinase inhibitor (TKI) for the treatment of Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), crizotinib, was successfully synthesized for use in positron emission tomography (PET). Sequential in vitro biological evaluation of fluoracetylcrizotinib and in vivo biodistribution studies of [¹⁸F]fluoroacetylcrizotinib demonstrated that the biological activity of the parent compound remained unchanged, with potent ALK kinase inhibition and effective tumor growth inhibition. These results show that [¹⁸F]fluoroacetylcrizotinib has the potential to be a promising PET ligand for use in NSCLC imaging. The utility of PET in this context provides a non-invasive, quantifiable method to inform on the pharmacokinetics of an ALK-inhibitor such as crizotinib prior to a clinical trial, as well as during a trial in the event of acquired drug resistance.     

Radiosynthesis and biological evaluation of an fluorine-18 labeled galactose derivative [18F]FPGal for imaging the hepatic asialoglycoprotein receptor

The asialoglycoprotein receptor (ASGPR) is abundantly expressed on the surface of hepatocytes where it recognizes and endocytoses glycoproteins with galactosyl and N-acetylgalactosamine groups. Given its hepatic distribution, the asialoglycoprotein receptor can be targeted by positron imaging agents to study liver function using PET imaging. In this study, the positron imaging agent [¹⁸F]FPGal was designed to specifically target hepatic asialoglycoprotein receptor and its effectiveness was assessed in in vitro and in vivo models. The radiosynthesis of [¹⁸F]FPGal required 50 min with total radiochemical yields of [¹⁸F]FPGal from [¹⁸F]fluoride as 10% (corrected radiochemical yield). The K_d of [¹⁸F]FPGal to ASGPR in HepG2 cells was 1.99 ± 0.05 mM. Uptake values of 0.55% were observed within 30 min of incubation with HepG2 cells, which could be blocked by 200 mM d(+)-galactose (<0.1%). In vivo biodistribution analysis showed that the liver accumulation of [¹⁸F]FPGal at 30 min was 4.47 ± 0.96% ID/g in normal mice compared to 1.33 ± 0.07% ID/g in hepatic fibrotic mice (P < 0.01). Reduced uptake in the hepatic fibrosis mouse models was confirmed through PET/CT images at 30 min. Compared to normal mice, the standard uptake value (SUV) in the hepatic fibrosis mice was significantly lower when assessed through dynamic data collection for 1 h. Therefore, [¹⁸F]FPGal is a feasible PET probe that provide insight into ASGPR related liver disease.     

Synthesis and preliminary evaluation of a new fluorine-18 labelled triazine derivative for PET imaging of cannabinoid CB2 receptor

Cannabinoid CB2 PET tracers are considered as a promising alternative to PBR/TSPO tracers for the in-vivo imaging of neuroinflammation. We describe here the synthesis and characterization of compound 3, a new potent and brain penetrating CB2 ligand based on an original triazine template. The PET tracer [¹⁸F]-dideutero-3 was prepared in a three steps radiosynthesis, and demonstrated significant uptake in rhesus macaque and baboon brain with a maximum SUV of about 0.7–0.9 g/mL, followed by a moderate washout over time.     

Synthesis and preclinical evaluation of 68Ga-PSMA-BCH for prostate cancer imaging

Prostate specific membrane antigen (PSMA) is a promising target for the diagnosis and therapy of prostate cancer. In this report, a NOTA-conjugated precursor, NOTA-PSMA (also named PSMA-BCH), was synthesized by peptide synthesizer with the chemical purity over 95%. ⁶⁸Ga-PSMA-BCH was obtained by radiolabeling NOTA-PSMA with ⁶⁸GaCl₃ with >99% radiochemical purity and 59–74?GBq/μmol specific activity. In vitro and in vivo study of ⁶⁸Ga-PSMA-BCH showed high stability, high uptake in PSMA-expressing cells and tumor, fast clearance and low non-target uptake. 22Rv1 tumors were clearly observed in micro-PET images of and showed good retention. Compared with ⁶⁸Ga-PSMA-617, ⁶⁸Ga-PSMA-BCH showed comparable tumor uptake and tumor-background ratios. Indicating ⁶⁸Ga-PSMA-BCH is a promising candidate for prostate cancer imaging and worthy of further clinical investigations.     

早期动态18F-FDG PET/CT成像在实体肿瘤评估中的应用

~(18)F-FDG PET/CT常规代谢成像反应肿瘤的葡萄糖代谢及乏氧情况,而~(18)F-FDG PET/CT早期动态成像能反映PET/CT成像早期肿瘤的灌注情况。由于肿瘤的异质性,在早期动态~(18)F-FDG PET/CT成像,即~(18)F-FDG PET/CT灌注成像中,存在独立于常规60 min~(18)F-FDG PET/CT代谢成像的SUVmax(最大标准摄取值)高摄取区。因此,在临床工作中应用~(18)F-FDG PET/CT早期动态成像,能够进一步对实体肿瘤的活性区域进行评估,能够更好评价患者预后、完善治疗方案。当前~(18)F-FDG早期动态成像已经应用在肝癌、肾癌以及膀胱癌等实体肿瘤诊断中。早期动态~(18)F-FDG PET/CT成像结合常规标准~(18)F-FDG PET/CT代谢成像,对实体肿块进行一站式成像方法,能够更好的对肿瘤进行评估。     

Synthesis and evaluation of 18F labeled crizotinib derivative [18F]FPC as a novel PET probe for imaging c-MET-positive NSCLC tumor

c-MET-positive NSCLC is an important subtype accounting for about 5%~22% of lung cancer. NSCLC patients with activating c-MET are intensively sensitive to c-MET selective receptor tyrosine kinase (RTK) inhibitors, so we aimed to develop a specific PET probe targeting to c-MET-positive NSCLC for potential patients screened by PET/CT. Herein, PET tracer ¹⁸F-radiolabeled crizotinib derivative ([¹⁸F]FPC) was successfully achieved through a simple one-step ¹⁸F-labeling method. [¹⁸F]FPC PET imaging on c-MET-positive (as well as blocking group) and negative NSCLC models were further evaluated, and results showed that [¹⁸F]FPC was effective as a PET imaging probe that targeted c-MET-positive tumor. Therefore, [¹⁸F]FPC could be a potential PET imaging probe for NSCLC tumor which was sensitive to c-MET-TKIs. By virtue of this property, it will benefit NSCLC patients for c-MET-TKI treatment.     

Radiosynthesis,biological evaluation and preliminary microPET study of 18F-labeled 5-resorcinolic triazolone derivative based on ganetespib targeting HSP90

Heat-shock protein 90 (HSP90) is a molecular chaperone that activates oncogenic transformation in several solid tumors, including lung and breast cancers. Ganetespib, a most promising candidate among several HSP90 inhibitors under clinical trials, has entered Phase III clinical trials for cancer therapy. Despite numerous evidences validating HSP90 as a target of anticancer, there are few studies on PET agents targeting oncogenic HSP90. In this study, we synthesized and biologically evaluated a novel ¹⁸F-labeled 5-resorcinolic triazolone derivative (1, [¹⁸F]PTP-Ganetespib) based on ganetespib. [¹⁸F]PTP-Ganetespib was labeled by click chemistry of Ganetespib-PEG-Alkyne (10) and [¹⁸F]PEG-N₃ (11) with 37.3?±?5.11% of radiochemical yield and 99.7?±?0.09% of radiochemical purity. [¹⁸F]PTP-Ganetespib showed proper LogP (0.96?±?0.06) and good stability in human serum over 97% for 2?h. [¹⁸F]PTP-Ganetespib showed high uptakes in breast cancer cells containing triple negative breast cancer (TNBC) MDA-MB-231 and Her2-negative MCF-7 cells, which are target breast cancer cell lines of HSP90 inhibitor, ganetespib, as an anticancer. Blocking of HSP90 by the pretreatment of ganetespib exhibited significantly decreased accumulation of [¹⁸F]PTP-Ganetespib in MDA-MB-231 and MCF-7 cells, indicating the specific binding of [¹⁸F]PTP-Ganetespib to MDA-MB-231 and MCF-7 cells with high HSP90 expression. In the biodistribution and microPET imaging studies, the initial uptake into tumor was weaker than in other thoracic and abdominal organs, but [¹⁸F]PTP-Ganetespib was retained relatively longer in the tumor than other organs. The uptake of [¹⁸F]PTP-Ganetespib in tumors was not sufficient for further development as a tumor-specific PET imaging agent by itself, but this preliminary PET imaging study of [¹⁸F]PTP-Ganetespib can be basis for developing new PET imaging agents based on HSP90 inhibitor, ganetespib.     

Radiosynthesis and in vivo evaluation of [11C]MOV as a PET imaging agent for COX-2

Radiosynthesis and in vivo evaluation of [¹¹C]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (methoxy analogue of valdecoxib, [¹¹C]MOV), a COX-2 inhibitor, was conducted in rat and baboon. Synthesis of the reference standard MOV (3), and its desmethyl precursor 2 for radiolabeling were performed using 1,2-diphenylethan-1-one as the starting material in five steps with 15% overall yield. Radiosynthesis of [¹¹C]MOV was accomplished in 40?±?10% yield and?>99% radiochemical purity by reacting the precursor 2 in dimethyl formamide (DMF) with [¹¹C]CH₃I followed by removal of the dimethoxytrityl (DMT) protective group using trifluroacetic acid. PET studies in anesthetized baboon showed very low uptake and homogeneous distribution of [¹¹C]MOV in brain. The radioligand underwent rapid metabolism in baboon plasma. MicroPET studies in male Sprague Dawley rats revealed [¹¹C]MOV binding in lower thorax. The tracer binding in rats was partially blocked in heart and duodenum by the administration of 1?mg/kg oral dose of COX-2 inhibitor valdecoxib.     

Synthesis and evaluation of the novel 2-[18F]fluoro-3-propoxy-triazole-pyridine-substituted losartan for imaging AT1 receptors

The 2-[¹⁸F]fluoro-3-pent-4-yn-1-yloxypyridine ([¹⁸F]FPyKYNE) analog of the potent non-peptide angiotensin II type 1 receptor (AT₁R) blocker losartan was produced via click chemistry linking [¹⁸F]FPyKYNE to azide-modified tetrazole-protected losartan followed by TFA deprotection. Preliminary small animal imaging with positron emission tomography (PET) in rats displayed high uptake in the kidneys with good contrast to surrounding tissue. Rat metabolism displayed the presence of 23% unchanged tracer in plasma at 30 min. Upon co-administration with AT₁R blocker candesartan (2.5, 5 and 10 mg/kg), a dose-dependent reduction (47–65%) in tracer uptake was observed in the kidney, while no difference was observed following AT₂R blocker PD123,319 (5 mg/kg), indicating binding selectivity for AT₁R over AT₂R and potential for imaging AT₁R using PET.     

Radiosynthesis and preclinical evaluation of [18F]FEM as a potential novel PET probe for tumor imaging

In the 21st century, the incidence and mortality of cancer, one of the most challenging diseases in the world, have rapidly increased. The purpose of this study was to develop 2-(2-[¹⁸F]fluoroethoxy)ethyl 4-methylbenzenesulfonate ([¹⁸F]FEM) as a positron emission tomography (PET) agent for tumor imaging. In this study, [¹⁸F]FEM was synthesized with a good radiochemical yield (45.4 ± 5.8%), high specific radioactivity (over 25 GBq/μmol), and commendable radiochemical purity (over 99%). The octanol/water partition coefficient of [¹⁸F]FEM was 1.44 ± 0.04. The probe demonstrated good stability in vitro (phosphate-buffered saline (PBS) and mouse serum (MS)), and binding specificity to five different tumor cell lines (A549, PC-3, HCC827, U87, and MDA-MB-231). PET imaging of tumor-bearing mice showed that [¹⁸F]FEM specifically accumulated at the tumor site of the five different tumor cell lines. The average tumor-to-muscle (T/M) ratio was over 2, and the maximum T/M values reached about 3.5. The biodistribution and dynamic PET imaging showed that most probes were metabolized by the liver, whereas a small part was metabolized by the kidney. Moreover, dynamic brain images and quantitative data showed [¹⁸F]FEM can quickly cross the blood brain barrier (BBB) and quickly fade out, thereby suggesting it may be a promising candidate probe for the imaging of brain tumors. The presented results demonstrated that [¹⁸F]FEM is a promising probe for tumor PET imaging.     

Synthesis and preliminary biological evaluation of a novel P2X7R radioligand [18F]IUR-1601

The reference standard IUR-1601 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-fluoroethyl)-5-oxopyrrolidine-2-carboxamide) was synthesized from tert-butyl (S)-5-oxopyrrolidine-2-carboxylate, fluoroethylbromide, and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 12% in three steps. The target tracer [¹⁸F]IUR-1601 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-[¹⁸F]fluoroethyl)-5-oxopyrrolidine-2-carboxamide) was synthesized from desmethyl-GSK1482160 with 2-[¹⁸F]fluoroethyl tosylate, prepared from 1,2-ethylene glycol-bis-tosylate and K[¹⁸F]F/Kryptofix2.2.2, in two steps and isolated by HPLC combined with SPE in 1–3% decay corrected radiochemical yield. The radiochemical purity was >99%, and the molar activity at end of bombardment (EOB) was 74–370?GBq/μmol. The potency of IUR-1601 in comparison with GSK1482160 was determined by a radioligand competitive binding assay using [¹¹C]GSK1482160, and the binding affinity K_i values for IUR-1601 and GSK1482160 are 4.31 and 5.14?nM, respectively.     

Synthesis and in vitro evaluation of [18F]BMS-754807: A potential PET ligand for IGF-1R

Radiosynthesis and in vitro evaluation of [¹⁸F](S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide ([¹⁸F]BMS-754807 or [¹⁸F]1) a specific IGF-1R inhibitor was performed. [¹⁸F]1 demonstrated specific binding in vitro to human cancer tissues. Synthesis of reference standard 1 and corresponding bromo derivative (1a), the precursor for radiolabeling were achieved from 2,4-dichloropyrrolo[2,1-f][1,2,4]triazine (4) in three steps with 50% overall yield. The radioproduct was obtained in 8% yield by reacting 1a with [¹⁸F]TBAF in DMSO at 170 °C at high radiochemical purity and specific activity (1–2 Ci/μmol, N = 10). The proof of concept of IGF-IR imaging with [¹⁸F]1 was demonstrated by in vitro autoradiography studies using pathologically identified surgically removed grade IV glioblastoma, breast cancer and pancreatic tumor tissues. These studies indicate that [¹⁸F]1 can be a potential PET tracer for monitoring IGF-1R.     

Improved radiosynthesis and preliminary in vivo evaluation of the 11C-labeled tetrazine [11C]AE-1 for pretargeted PET imaging

Pretargeted nuclear imaging based on the ligation between tetrazines and nano-sized targeting agents functionalized with trans-cyclooctene (TCO) has recently been shown to improve both imaging contrast and dosimetry in nuclear imaging of nanomedicines. Herein, we describe the improved radiosynthesis of a ¹¹C-labeled tetrazine ([¹¹C]AE-1) and its preliminary evaluation in both mice and pigs. Pretargeted imaging in mice was carried out using both a new TCO-functionalized polyglutamic acid and a previously reported TCO-functionalized bisphosphonate system as targeting agents. Unfortunately, pretargeted imaging was not successful using these targeting agents in pair with [¹¹C]AE-1. However, brain imaging in pig indicated that the tracer crossed the blood-brain-barrier. Hence, we suggest that this tetrazine scaffold could be used as a starting point for the development of pretargeted brain imaging, which has so far been a challenging task.     

Preclinical evaluation of a CXCR4-specific 68Ga-labelled TN14003 derivative for cancer PET imaging

Molecular imaging is an ideal platform for non-invasive detection and assessment of cancer. In recent years, the targeted imaging of CXCR4, a chemokine receptor that has been associated with tumour metastasis, has become an area of intensive research. In our pursuit of a CXCR4-specific radiotracer, we designed and synthesised a novel derivative of the CXCR4 peptidic antagonist TN14003, CCIC16, which is amenable to radiolabelling by chelation with a range of PET and SPECT radiometals, such as ⁶⁸Ga, ⁶⁴Cu and ¹¹¹In as well as ¹⁸F (Al¹⁸F). Potent in vitro binding affinity and inhibition of signalling-dependent cell migration by unlabelled CCIC16 were confirmed by a threefold uptake in CXCR4-over-expressing cells compared to their isogenic counterparts. Furthermore, in vivo experiments demonstrated the favourable pharmacokinetic properties of the ⁶⁸Ga-labelled tracer ⁶⁸Ga–CCIC16, along with its CXCR4-specific accumulation in tissues with desirable contrast (tumour-to-muscle ratio: 9.5). The specificity of our tracer was confirmed by blocking experiments. Taking into account the attractive intrinsic PET imaging properties of ⁶⁸Ga, the comprehensive preclinical evaluation presented here suggests that ⁶⁸Ga–CCIC16 is a promising PET tracer for the specific imaging of CXCR4-expressing tumours.     

68Ga labeled Erlotinib: A novel PET probe for imaging EGFR over-expressing tumors

Molecular imaging using radiolabeled Tyrosine Kinase Inhibitors (TKI) is a promising strategy for detection and staging of EGFR-positive cancers. A novel analogue of one such TKI, Erlotinib has been developed for PET imaging by derivatizing the parent Erlotinib molecule for conjugation with the bifunctional chelator p-SCN-Bn-NOTA towards radiolabeling with ⁶⁸Ga. NOTA-Erlotinib conjugate was synthesized and characterized by NMR and ESI-MS techniques. The conjugate was radiolabeled with ⁶⁸Ga in 95 ± 2% yield, as evidenced by HPLC characterization. The log P value of ⁶⁸Ga-NOTA-Erlotinib was – (0.6 ± 0.1). The ⁶⁸Ga-NOTA-Erlotinib conjugate was characterized using its ^natGa-NOTA-Erlotinib surrogate. Cell viability studies showed that the NOTA-Erlotinib conjugate retained the biological efficacy of the parent Erlotinib molecule. Further, ⁶⁸Ga-NOTA-Erlotinib exhibited an uptake of 9.8 ± 0.4% in A431 cells which was inhibited by 55.1 ± 0.2% on addition of cold Erlotinib (10 µg) confirming the specificity of the radioconjugate for EGFR expressing cells. In the biodistribution studies carried out in tumor bearing SCID mice, ⁶⁸Ga-NOTA-Erlotinib conjugate showed moderate tumor accumulation (1.5 ± 0.1% ID/g at 30 min p.i.; 0.7 ± 0.2% ID/g at 1 h p.i.). Hepatobiliary clearance of the radioconjugate was observed. The ⁶⁸Ga-NOTA-Erlotinib conjugate was found to have high in vivo stability as determined by the metabolite analysis study using urine sample of the Swiss mice injected with the preparation. The overall properties of ⁶⁸Ga-NOTA-Erlotinib are promising and merit further exploration. To the best of our knowledge, this is the first report on the design of a ⁶⁸Ga labeled Erlotinib for PET imaging of EGFR and opens avenues for the successful development of ⁶⁸Ga labeled TKI for imaging of EGFR over-expressing tumors.     

Fluorine-18 click radiosynthesis and microPET/CT evaluation of a small peptide-a potential PET probe for carbonic anhydrase IX

Carbonic anhydrase IX (CA IX) is the first carbonic anhydrase found to be associated with cancer that is over-expressed in a variety of human solid tumors. As a surrogate marker for hypoxia, the expression of CA IX is strongly upregulated in hypoxic tumors by hypoxia and hypoxia-inducible factor 1a (HIF-1a). In our pursuit of a CA IX-specific PET probe, we designed and synthesized a peptide-based CA IX imaging probe by the efficient click reaction of 1,3-dipolar cycloaddition of terminal alkynes and organic azides. The probe ¹⁸F-CA IX-P1-4-10 was obtained with a radiochemical yield of 35–45% (n?=?5) and radiochemical purity of >99% in 70–80?min (HPLC purification time included). ¹⁸F-CA IX-P1-4-10 had good stability in phosphate buffered saline (PBS), but about 51% peptide degradation was detected in new-born calf serum (NBCS) after incubation. Preliminary microPET/CT experiments demonstrated a specific uptake of ¹⁸F-CA IX-P1-4-10 in HT29 tumor and the uptake of ¹⁸F-CA IX-P1-4-10 was blocked by peptide CA IX-P1-4-10-Yne pretreatment. Immunohistochemical staining and western blotting studies confirmed the HT29 tumor was CA IX-positive which further proved tumor accumulation of ¹⁸F-CA IX-P1-4-10 was correlated with CA IX expression. The results suggest that ¹⁸F-CA IX-P1-4-10 is a promising PET tracer for the specific imaging of CA IX-expressing tumors at the molecular level.     

Radiation dosimetry of 18F-flurocholine PET/CT studies in prostate cancer patients

PurposeWe aimed to evaluate the Equivalent Doses (H_Ts) to highly exposed organs as well as the Effective Dose (ED) for ¹⁸F-fluorocholine PET/CT scan in the follow-up of prostate cancer patients.MethodsFifty patients were administered with ¹⁸F-fluorocholine. The activities in organs with the highest uptake were derived by region-of-interest (ROI) analysis. OLINDA/EXM1.0 and Impact software were used to assess ED for the administered ¹⁸F-fluorocholine and CT scan, respectively, and the ¹⁸F-fluorocholine and CT-scan EDs summed to yield the total ED for the PET/CT procedure.ResultsThe calculated ¹⁸F-fluorocholine and CT scans EDs based on ICRP Publication 103 were 5.2 mSv/300 MBq and 6.7 mSv, respectively. The ¹⁸F-fluorocholine H_Ts to the liver, kidneys, spleen and pancreas were about threefold higher than those from the CT, which contributed a greater proportion of the total ED than the ¹⁸F-fluorocholine did.ConclusionsFor ¹⁸F-fluorocholine PET/CT procedures, about 40% of the ED is contributed by administered ¹⁸F-fluorocholine and 60% by the CT scan. The kidneys and liver were the highly exposed organs. Considering the large number of diagnostic procedures oncology patients undergo, radiation dosimetry is important in relation to the stochastic risk of such procedures.     

Synthesis and biological evaluation of novel F-18 labeled pyrazolo[1,5-a]pyrimidine derivatives: potential PET imaging agents for tumor detection

Two novel pyrazolo[1,5-a]pyrimidine derivatives, 7-(2-[¹⁸F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([¹⁸F]FEMPPC, [¹⁸F]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[¹⁸F]fluoro-4-nitrobenzamide ([¹⁸F]FCMPPN, [¹⁸F]2), have been designed and successively labeled with ¹⁸F by the nucleophilic substitution employing tosylate and nitryl as leaving groups, respectively. The radiochemical synthesis of both compounds was completed within 60 min with final high-performance liquid chromatography purification included. The corresponding radiochemical yields (without decay correction) were approximately 35% and 30%, respectively. Meanwhile, we compared the uptake characteristics of [¹⁸F]1 and [¹⁸F]2 with those of [¹⁸F]FDG and L-[¹⁸F]FET in S180 tumor cells. Furthermore, the tumor uptake of [¹⁸F]1 and [¹⁸F]2 was assessed in mice bearing S180 tumor and compared with [¹⁸F]FDG and L-[¹⁸F]FET in the same animal model. In vitro cell uptake studies showed [¹⁸F]1 had higher uptake than [¹⁸F]FDG, [¹⁸F]2 and L-[¹⁸F]FET over the 2 h period. In ex vivo biodistribution showed tumor/brain uptake ratios of [¹⁸F]2 were 12.35, 10.44, 8.69 and 5.13 at 15 min, 30 min, 60 min and 120 min post-injection, much higher than those of L-[¹⁸F]FET (2.43, 2.54, 2.93 and 2.95) and [¹⁸F]FDG (0.59, 0.61, 1.02 and 1.33) at the same time point. What’s more, the uptake of [¹⁸F]1 in tumor was 1.88, 4.37, 5.51, 2.95 and 2.88 at 5 min, 15 min, 30 min, 60 min and 120 min post-injection, respectively. There was a remarkable increasing trend before 30 min. The same trend was present for L-[¹⁸F]FET before 30 min and [¹⁸F]FDG before 60 min. Additionally, the tumor/brain uptake ratios of [¹⁸F]1 were superior to those of [¹⁸F]FDG at all the selected time points, the tumor/muscle and tumor/blood uptake ratios of [¹⁸F]1 at 30 min were higher than those of L-[¹⁸F]FET at the same time point. MicroPET image of [¹⁸F]1 administered into S180 tumor-bearing mouse acquired at 30 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggest that compound [¹⁸F]1 could be a new probe for PET tumor imaging.