PurposeDespite current advances in PET/CT systems, blood sampling still remains the standard method to obtain the radiotracer input function for tracer kinetic modelling. The purpose of this study was to validate the use of image-derived input functions (IDIF) of the carotid and femoral arteries to measure the arterial input function (AIF) in PET imaging. The data were obtained from two different research studies, one using 18F-FDG for brain imaging and the other using 11C-acetate and 18F-fluoro-6-thioheptadecanoic acid (18F-FTHA) in femoral muscles.MethodsThe method was validated with two phantom systems. First, a static phantom consisting of syringes of different diameters containing radioactivity was used to determine the recovery coefficient (RC) and spill-in factors. Second, a dynamic phantom built to model bolus injection and clearance of tracers was used to establish the correlation between blood sampling, AIF and IDIF. The RC was then applied to the femoral artery data from PET imaging studies with 11C-acetate and 18F-FTHA and to carotid artery data from brain imaging with 18F-FDG. These IDIF data were then compared to actual AIFs from patients.ResultsWith 11C-acetate, the perfusion index in the femoral muscle was 0.34±0.18 min−1 when estimated from the actual time–activity blood curve, 0.29±0.15 min−1 when estimated from the corrected IDIF, and 0.66±0.41 min−1 when the IDIF data were not corrected for RC. A one-way repeated measures (ANOVA) and Tukey’s test showed a statistically significant difference for the IDIF not corrected for RC (p<0.0001). With 18F-FTHA there was a strong correlation between Patlak slopes, the plasma to tissue transfer rate calculated using the true plasma radioactivity content and the corrected IDIF for the femoral muscles (vastus lateralis r=0.86, p=0.027; biceps femoris r=0.90, p=0.017). On the other hand, there was no correlation between the values derived using the AIF and those derived using the uncorrected IDIF. Finally, in the brain imaging study with 18F-FDG, the cerebral metabolic rate of glucose (CMRglc) measured using the uncorrected IDIF was consistently overestimated. The CMRglc obtained using blood sampling was 13.1±3.9 mg/100 g per minute and 14.0±5.7 mg/100 g per minute using the corrected IDIF (r2=0.90).ConclusionCorrectly obtained, carotid and femoral artery IDIFs can be used as a substitute for AIFs to perform tracer kinetic modelling in skeletal femoral muscles and brain analyses.

Cyclotron production of 99m Tc is a promising route to supply 99m Tc radiopharmaceuticals. Higher 99m Tc yields can be obtained with medium-energy cyclotrons in comparison to those dedicated to PET isotope production. To take advantage of this capability, evaluation of the radioisotopic purity of 99m Tc produced at medium energy (20)(21)(22)(23)(24) and its impact on image quality and dosimetry was required. Methods: Thick 100 Mo (99.03% and 99.815%) targets were irradiated with incident energies of 20, 22, and 24 MeV for 2 or 6 h. The targets were processed to recover an effective thickness corresponding to approximately 5-MeV energy loss, and the resulting sodium pertechnetate 99m Tc was assayed for chemical, radiochemical, and radionuclidic purity. Radioisotopic content in final formulation was quantified using g-ray spectrometry. The internal radiation dose for 99m Tc-pertechnetate was calculated on the basis of experimentally measured values and biokinetic data in humans. Planar and SPECT imaging were performed using thin capillary and water-filled Jaszczak phantoms. Results: Extracted sodium pertechnetate 99m Tc met all provisional quality standards. The formulated solution for injection had a pH of 5.0−5.5, contained greater than 98% of radioactivity in the form of pertechnetate ion, and was stable for at least 24 h after formulation. Radioisotopic purity of 99m Tc produced with 99.03% enriched 100 Mo was greater than 99.0% decay corrected to the end of bombardment (EOB). The radioisotopic purity of 99m Tc produced with 99.815% enriched 100 Mo was 99.98% or greater (decay corrected to the EOB). The estimated dose increase relative to 99m Tc without any radionuclidic impurities was below 10% for sodium pertechnetate 99m Tc produced from 99.03% 100 Mo if injected up to 6 h after the EOB. For 99.815% 100 Mo, the increase in effective dose was less than 2% at 6 h after the EOB and less than 4% at 15 h after the EOB when the target was irradiated at an incident energy of 24 MeV. Image spatial resolution and contrast with cyclotron-produced 99m Tc were equivalent to those obtained with 99m Tc eluted from a conventional generator. Conclusion: Clinical-grade sodium pertechnetate 99m Tc was produced with a cyclotron at medium energies. Quality control procedures and release specifications were drafted as part of a clinical trial application that received approval from Health Canada. The results of this work are intended to contribute to establishing a regulatory framework for using cyclotron-produced 99m Tc in routine clinical practice. The radioisotope 99m Tc remains indispensable in nuclear imaging. 99m Tc is usually obtained from generators containing the mother isotope, 99 Mo, which in turn is made from highly enriched 235 U ($20%, typically 93%) in nuclear reactors. 99m Tc is eluted in the form of sodium pertechnetate and can be used as is or as the starting material for other 99m Tc radiopharmaceuticals used in a variety of diagnostic applications. Cyclotron production of 99m Tc could be a viable alternativ...

After encouraging preclinical and human dosimetry results for the novel estrogen receptor (ER) PET radiotracer 4-fluoro-11β-methoxy-16α-F-fluoroestradiol (F-4FMFES), a phase II clinical trial was initiated to compare the PET imaging diagnostic potential of F-4FMFES with that of 16α-F-fluoroestradiol (F-FES) in ER-positive (ER+) breast cancer patients. Patients diagnosed with ER+ breast cancer ( = 31) were recruited for this study, including 6 who underwent mastectomy or axillary node dissection. For each patient, F-FES andF-4FMFES PET/CT scans were done sequentially (within a week) and in random order. One hour after injection of either radiotracer, a head-to-thigh static scan with a 2-min acquisition per bed position was obtained. Blood samples were taken at different times after injection to assess each tracer metabolism by reverse-phase thin-layer chromatography. The SUV of nonspecific tissues and the SUV of the tumor were evaluated for each detected lesion, and tumor-to-nonspecific organ ratios were calculated. Blood metabolite analysis 60 min after injection of the tracer showed a 2.5-fold increase in metabolic stability ofF-4FMFES over F-FES. Although for most fociF-4FMFES PET had an SUV similar to that of F-FES PET, tumor contrast improved substantially in all cases. Lower uptake was consistently observed in nonspecific tissues forF-4FMFES, notably a 4-fold decrease in blood-pool activity as compared with F-FES. Consequently, image quality was considerably improved usingF-4FMFES, with lower overall background activity. As a result, F-4FMFES successfully identified 9 more lesions thanF-FES. This phase II study with ER+ breast cancer patients showed thatF-4FMFES PET achieves a lower nonspecific signal and better tumor contrast than F-FES PET, resulting in improved diagnostic confidence and lower false-negative diagnoses.

Semiconductor micro and nanofabrication lithography techniques for application in microelectronics as well as in micromechanics and optoelectronics can gain significantly from using a dry resist process, since it enables the deposition of a very uniform lithographically sensitive layer on a potentially very small area. This would otherwise be extremely difficult to achieve by using a traditional spin coated resist, such as poly(methylmethacrylate) (PMMA). We demonstrate the use of an electron sensitive sterol based evaporated electron beam resist to fabricate high-resolution features (down to 100 nm) on a small surface area. This electron beam resist has a sensitivity comparable to PMMA and is deposited using a simple thermal evaporation. Two practical applications are explored: first, this resist makes it possible to fabricate a Fresnel zone plate lens on the tip of an optical fiber in order to demonstrate the principle and the potential of highly efficient coupling of diode laser emission into the fiber; second, we use this evaporated electron beam resist in order to pattern an optical diffractive element on the facet of a semiconductor laser.