TMSOTf assisted synthesis of 2’-deoxy-2’-[18F] fluoro-β-D-arabinofuranosylcytosine ([18F] FAC)

[18F]FAC (2’-deoxy-2’-[18F]fluoro-β-D-arabinofuranosylcytosine, 1) is a versatile probe for imaging deoxycytidine kinase (dCK) expression levels in vivo. dCK is responsible for phosphorylation of deoxycytidine (dC, 2) and other nucleoside analogs, plays a key role in immune activation and has demonstrated to be one of the key enzymes in activating nucleoside based drugs including gemcitabine. Reported synthesis of [18F]FAC is high yielding but is quite challenging requiring bromination using HBr and careful drying of excess HBr which is critical for successful synthesis. Here in we report a simplified trimethylsilyl trifluoromethanesulfonate (TMSOTf) assisted synthesis of [18F]FAC eliminating the need of bromination and drying. [18F]FAC (β-anomer) was synthesized with average isolated decay corrected yield of 10.59 + 4.2% (n = 6) with radiochemical purity of \u3e98% and total synthesis time of 158 + 19 min

Quantitative Modeling of Cerenkov Light Production Efficiency from Medical Radionuclides

There has been recent and growing interest in applying Cerenkov radiation (CR) for biological applications. Knowledge of the production efficiency and other characteristics of the CR produced by various radionuclides would help in accessing the feasibility of proposed applications and guide the choice of radionuclides. To generate this information we developed models of CR production efficiency based on the Frank-Tamm equation and models of CR distribution based on Monte-Carlo simulations of photon and β particle transport. All models were validated against direct measurements using multiple radionuclides and then applied to a number of radionuclides commonly used in biomedical applications. We show that two radionuclides, Ac-225 and In-111, which have been reported to produce CR in water, do not in fact produce CR directly. We also propose a simple means of using this information to calibrate high sensitivity luminescence imaging systems and show evidence suggesting that this calibration may be more accurate than methods in routine current use

Pilot study of PET imaging of 124I-iodoazomycin galactopyranoside (IAZGP), a putative hypoxia imaging agent, in patients with colorectal cancer and head and neck cancer

Background: Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. We performed a clinical study to evaluate the safety, biodistribution, and imaging characteristics of 124I-IAZGP in patients with advanced colorectal cancer and head and neck cancer using serial positron emission tomography (PET) imaging. Methods: Ten patients underwent serial whole-torso (head/neck to pelvis) PET imaging together with multiple whole-body counts and blood sampling. These data were used to generate absorbed dose estimates to normal tissues for 124I-IAZGP. Tumors were scored as either positive or negative for 124I-IAZGP uptake. Results: There were no clinical toxicities or adverse effects associated with 124I-IAZGP administration. Clearance from the whole body and blood was rapid, primarily via the urinary tract, with no focal uptake in any parenchymal organ. The tissues receiving the highest absorbed doses were the mucosal walls of the urinary bladder and the intestinal tract, in particular the lower large intestine. All 124I-IAZGP PET scans were interpreted as negative for tumor uptake. Conclusions: It is safe to administer 124I-IAZGP to human subjects. However, there was insufficient tumor uptake to support a clinical role for 124I-IAZGP PET in colorectal cancer and head and neck cancer patients. Trial registration: ClinicalTrials.gov NCT0058827

Accuracy and Precision of Radioactivity Quantification in Nuclear Medicine Images

The ability to reliably quantify activity in nuclear medicine has a number of increasingly important applications. Dosimetry for targeted therapy treatment planning or for approval of new imaging agents requires accurate estimation of the activity in organs, tumors, or voxels at several imaging time points. Another important application is the use of quantitative metrics derived from images, such as the standard uptake value commonly used in positron emission tomography (PET), to diagnose and follow treatment of tumors. These measures require quantification of organ or tumor activities in nuclear medicine images. However, there are a number of physical, patient, and technical factors that limit the quantitative reliability of nuclear medicine images. There have been a large number of improvements in instrumentation, including the development of hybrid single-photon emission computed tomography/computed tomography and PET/computed tomography systems, and reconstruction methods, including the use of statistical iterative reconstruction methods, which have substantially improved the ability to obtain reliable quantitative information from planar, single-photon emission computed tomography, and PET images. Semin Nucl Med 42:208-218 (C) 2012 Elsevier Inc. All rights reserved

18F-fluoromisonidazole predicts evofosfamide uptake in pancreatic tumor model

Abstract Background Quantitative imaging can facilitate patient stratification in clinical trials. The hypoxia-activated prodrug evofosfamide recently failed a phase III trial in pancreatic cancer. However, the study did not attempt to select for patients with hypoxic tumors. We tested the ability of 18F-fluoromisonidazole to predict evofosfamide uptake in an orthotopic xenograft model (BxPC3). Methods Two forms of evofosfamide were used: (1) labeled on the active moiety (3H) and (2) on the hypoxia targeting nitroimidazole group (14C). Tumor uptake of evofosfamide and 18F-fluoromisonidazole was counted ex vivo. Autoradiography of 14C and 18F coupled with pimonidazole immunohistochemistry revealed the spatial distributions of prodrug, radiotracer, and hypoxia. Results There was significant individual variation in 18F-fluoromisonidazole uptake, and a significant correlation between normalized 18F-fluoromisonidazole and both 3H-labeled and 14C-labeled evofosfamide. 18F-fluoromisonidazole and 14C-evofosfamide both localized in hypoxic regions as identified by pimonidazole. Conclusion 18F-fluoromisonidazole predicts evofosfamide uptake in a preclinical pancreatic tumor model

A Recommendation for Revised Dose Calibrator Measurement Procedures for ⁸⁹Zr and ¹²⁴I

<div><p>Because of their chemical properties and multiday half lives, iodine-124 and zirconium-89 are being used in a growing number of PET imaging studies. Some aspects of their quantitation, however, still need attention. For ⁸⁹Zr the PET images should, in principle, be as quantitatively accurate as similarly reconstructed ¹⁸F measurements. We found, however, that images of a 20 cm well calibration phantom containing ⁸⁹Zr underestimated the activity by approximately 10% relative to a dose calibrator measurement (Capintec CRC-15R) using a published calibration setting number of 465. PET images of ¹²⁴I, in contrast, are complicated by the contribution of decays in cascade that add spurious coincident events to the PET data. When these cascade coincidences are properly accounted for, quantitatively accurate images should be possible. We found, however, that even with this correction we still encountered what appeared to be a large variability in the accuracy of the PET images when compared to dose calibrator measurements made using the calibration setting number, 570, recommended by Capintec. We derive new calibration setting numbers for ⁸⁹Zr and ¹²⁴I based on their 511 keV photon peaks as measured on an HPGe detector. The peaks were calibrated relative to an ¹⁸F standard, the activity level of which was precisely measured in a dose calibrator under well-defined measurement conditions. When measuring ⁸⁹Zr on a Capintec CRC-15R we propose the use of calibration setting number 517. And for ¹²⁴I, we recommend the use of a copper filter surrounding the sample and the use of calibration setting number 494. The new dose calibrator measurement procedures we propose will result in more consistent and accurate radioactivity measurements of ⁸⁹Zr and ¹²⁴I. These and other positron emitting radionuclides can be accurately calibrated relative to ¹⁸F based on measurements of their 511 keV peaks and knowledge of their relative positron abundances.</p></div