Production of Medical Radioisotopes with High Specific Activity in Photonuclear Reactions with γ\gamma Beams of High Intensity and Large Brilliance

We study the production of radioisotopes for nuclear medicine in $(\gamma,x{\rm n}+y{\rm p})$ photonuclear reactions or ($\gamma,\gamma'$) photoexcitation reactions with high flux [($10^{13}-10^{15}$)$\gamma$/s], small diameter $\sim (100 \, \mu$m$)^2$ and small band width ($\Delta E/E \approx 10^{-3}-10^{-4}$) $\gamma$ beams produced by Compton back-scattering of laser light from relativistic brilliant electron beams. We compare them to (ion,$x$n$+ y$p) reactions with (ion=p,d,$\alpha$) from particle accelerators like cyclotrons and (n,$\gamma$) or (n,f) reactions from nuclear reactors. For photonuclear reactions with a narrow $\gamma$ beam the energy deposition in the target can be managed by using a stack of thin target foils or wires, hence avoiding direct stopping of the Compton and pair electrons (positrons). $(\gamma,\gamma')$ isomer production via specially selected $\gamma$ cascades allows to produce high specific activity in multiple excitations, where no back-pumping of the isomer to the ground state occurs. We discuss in detail many specific radioisotopes for diagnostics and therapy applications. Photonuclear reactions with $\gamma$ beams allow to produce certain radioisotopes, e.g. $^{47}$Sc, $^{44}$Ti, $^{67}$Cu, $^{103}$Pd, $^{117m}$Sn, $^{169}$Er, $^{195m}$Pt or $^{225}$Ac, with higher specific activity and/or more economically than with classical methods. This will open the way for completely new clinical applications of radioisotopes. For example $^{195m}$Pt could be used to verify the patient's response to chemotherapy with platinum compounds before a complete treatment is performed. Also innovative isotopes like $^{47}$Sc, $^{67}$Cu and $^{225}$Ac could be produced for the first time in sufficient quantities for large-scale application in targeted radionuclide therapy.Comment: submitted to Appl. Phys.

Localization of Tc-99m-GRP Analogs in GRPR-Expressing Tumors: Effects of Peptide Length and Neprilysin Inhibition on Biological Responses

The overexpression of gastrin-releasing peptide receptors (GRPRs) in frequently occurring human tumors has provided the opportunity to use bombesin (BBN) analogs as radionuclide carriers to cancer sites for diagnostic and therapeutic purposes. We have been alternatively exploring human GRP motifs of higher GRPR selectivity compared to frog BBN sequences aiming to improve pharmacokinetic profiles. In the present study, we compared two differently truncated human endogenous GRP motifs: GRP(14–27) and GRP(18–27). An acyclic tetraamine was coupled at the N-terminus to allow for stable binding of the SPECT radionuclide 99mTc. Their biological profiles were compared in PC-3 cells and in mice without or with coinjection of phosphoramidon (PA) to induce transient neprilysin (NEP) inhibitio

Incretin receptors in non-neoplastic and neoplastic thyroid C cells in rodents and humans: relevance for incretin-based diabetes therapy

While incretins are of great interest for the therapy of diabetes 2, the focus has recently been brought to the thyroid, since rodents treated with glucagon-like peptide-1 (GLP-1) analogs were found to occasionally develop medullary thyroid carcinomas. Incretin receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were therefore measured in various rodent and human thyroid conditions. In vitro GLP-1 and GIP receptor autoradiography were performed in normal thyroids, C-cell hyperplasia and medullary thyroid carcinomas in rodents. Receptor incidence and density were assessed and compared with the receptor expression in human thyroids, medullary thyroid carcinomas, and TT cells. GLP-1 receptors are expressed in C cells of normal rat and mice thyroids. Their density is markedly increased in rat C-cell hyperplasia and medullary thyroid carcinomas, where their incidence amounts to 100%. GIP receptors are neither detected in normal rodent thyroids nor in C-cell hyperplasia, but are present in all rat medullary thyroid carcinomas. No GLP-1 or GIP receptors are detected in normal human thyroids. Whereas only 27% of all human medullary thyroid carcinomas express GLP-1 receptors, up to 89% express GIP receptors in a high density. TT cells lack GLP-1 receptors but express GIP receptors. GLP-1 receptors are frequently expressed in non-neoplastic and neoplastic C cells in rodents while they are rarely detected in human C-cell neoplasia, suggesting species differences. Conversely, GIP receptors appear to be massively overexpressed in neoplastic C cells in both species. The presence of incretin receptors in thyroid C cell lesions suggests that this organ should be monitored before and during incretin-based therapy of diabetes