Achieving Balance as a Survival Strategy for a Small Cyclotron Facility

Positron emission tomography (PET) forms the rationale for several dozen new cyclotron installations across the world. The success of these small accelerators has resulted in an excess production capacity. This suggests fanning out as a regional distribution center or, as in our case, reaching out to provide Argonne Nat\u27l Lab with F-18 for the study of astrophysical reaction rates with radioactive ion beams. The challenge to scale up our target yields has greatly benefited our medical mission. The diversification vitalizes our PhD training, and the collegial relationship provides a needed measure of balance. Presented at the 14th International Conference on Cyclotrons and the Applications, Faure, Cape Town, South Africa, October 8-13, 1995

NEMA count-rate evaluation of the first and second generation of the Ecat Exact and Ecat Exact HR family of scanners

The first and second generation of the Exact and Exact HR family of scanners has been evaluated in terms of noise equivalent count rate (NEC) and count-rate capabilities. The new National Electrical Manufacturers Association standard was used for the evaluation. In spite of improved electronics and improved count-rate capabilities, the peak NEC was found to be fairly constant between the generations. The results are discussed in terms of the different electronic solutions for the two generations and its implications on system dead time and NEC count-rate capability

Addressing the Third Gamma Problem in PET

PET brings the promise of quantitative imaging of the in-vivo distribution of any positron emitting nuclide, a list with hundreds of candidates. All but a few of these, the pure positron emitters, have isotropic, coincident gamma rays that give rise to misrepresented events in the sinogram and in the resulting reconstructed image. Of particular interest are 10C, 14O, 38K, 52mMn, 60Cu, 61Cu, 94mTc, and 124I, each having high-energy gammas that are Compton-scattered down into the 511 keV window. The problems arising from the third gamma, and its accommodation by standard scatter correction algorithms, were studied empirically, employing three scanner models (CTI 933/04, CTI HR+, and GE Advance), imaging three phantoms (line source, NEMA scatter, and contrast/detail), with 18F or 38K and 72As mimicking 14O and 10C, respectively, in 2D and 3D modes. Five findings emerge directly from the image analysis. The third gamma: (1) does, obviously, tax the single event rate of the PET scanners, particularly in the absence of septa, from activity outside of the axial field of view; (2) does, therefore, tax the random rate, which is second order in singles, although the gamma is a prompt coincidence partner; (3) does enter the sinogram as an additional flat background, like randoms, but unlike scatter; (4) is not seriously misrepresented by the scatter algorithm which fits the correction to the wings of the sinogram and (5) does introduce additional statistical noise from the subsequent subtraction, but does not seriously compromise the detectability of lesions as seen in the contrast/detail phantom. As a safeguard against the loss of accuracy in image quantitation, fiducial sources of known activity are included in the field of view alongside of the subject. With this precaution, a much wider selection o f imaging agents can enjoy the advantages of positron emission tomography

hnRNP C1/C2 and Pur-beta proteins mediate induction of senescence by oligonucleotides homologous to the telomere overhang

BACKGROUND: Experimental disruption of the telomere overhang induces a potent DNA damage response and is the target of newly emerging cancer therapeutics. Introduction of T-oligo, an eleven-base oligonucleotide homologous to the 3′-telomeric overhang, mimics telomere disruption and induces DNA damage responses through activation of p53, p73, p95/Nbs1, E2F1, pRb, and other DNA damage response proteins. ATM (ataxia telangiectasia mutated) was once thought to be the primary driver of T-oligo-induced DNA damage responses; however, recent experiments have highlighted other key proteins that may also play a significant role. METHODS: To identify proteins associated with T-oligo, MM-AN cells were treated with biotinylated T-oligo or complementary oligonucleotide, cell lysates were run on SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis), and the protein bands observed after treatment of cells with T-oligo or complementary oligonucleotide were analyzed using mass spectrometry. To study the effect of T-oligo on expression of hnRNP C1/C2 (heterogeneous nuclear ribonucleoprotein C1 and C2) and purine-rich element binding proteins (Pur proteins), cells were treated with T-oligo, and immunoblotting experiments were performed. To determine their role in senescence, cells were treated with shRNA (short hairpin ribonucleic acid) against these proteins, and senescence was studied using the senescence associated beta-galactosidase assay. RESULTS: Using mass spectrometry, RNA-binding hnRNP C1/C2 and DNA-binding Pur proteins were found to associate with T-oligo. hnRNP C1/C2 exhibited increased expression (3.6–12.0-fold) in non-small-cell lung cancer (NSCLC) and in melanoma cells (4.5–5.2-fold), and Pur proteins exhibited increased expression of 2.2-fold in NSCLC and 2.0-fold in melanoma cells after T-oligo treatment. Experimental knockdown of hnRNP C1/C2 and Pur-beta completely abrogated T-oligo induced senescence in both MU melanoma and H358 NSCLC cells. Additionally, knockdown of Pur-beta prevented T-oligo-induced phosphorylation of p53, hypophosphorylation of pRb, and upregulation of E2F1, p21, and p53. CONCLUSION: These novel findings highlight proteins essential to T-oligo’s anticancer effects that may be of interest in telomere biology and cancer therapeutics

Achieving Balanced Resolution in Radiopharmacological Studies: Tc-Labeled BMS 194,796

Paper presented at the 12th International Symposium on Radiopharmaceutical Chemistry, Uppsala, Sweden, June 15-19, 1997