Cross-sections of spallation residues produced in 1.A GeV 208Pb on proton reactions

Spallation residues produced in 1 GeV per nucleon $^{208}$Pb on proton reactions have been studied using the FRagment Separator facility at GSI. Isotopic produc- tion cross-sections of elements from $_{61}$Pm to $_{82}$Pb have been measured down to 0.1 mb with a high accuracy. The recoil kinetic energies of the produced fragments were also determined. The obtained cross-sections agree with most of the few existing gamma-spectroscopy data. Data are compared with different intra nuclear-cascade and evaporation-fission models. Drastic deviations were found for a standard code used in technical applications.Comment: 4 pages, 3 figures, accepted for publication in Phys. Rev. Lett. Revised version May 12, 200

Evaluation of novel whole-body high-resolution rodent SPECT (Linoview) based on direct acquisition of linogram projections.

Studies of the biodistribution of radiolabeled compounds in rodents frequently are performed during the process of development of new pharmaceutical drugs. This article presents the evaluation of a new whole-body animal SPECT system, called the Linoview SPECT system. METHODS: Linoview SPECT is based on the linear orbit acquisition technique associated with slit-aperture collimators mounted on 4 pixelated CsI(Na) detectors composed of an array of small, individual crystal elements. Sliding iridium rods allow variation of the collimator aperture. Hot-rod and cold-rod phantoms filled with (99m)Tc were imaged. Mice were imaged, and kidney radioactivity was measured after injection of (99m)Tc-dimercaptosuccinic acid and (111)In-diethylenetriaminepentaacetic acid-d-Phe(1)-octreotide ((111)In-pentetreotide; Octreo-Scan(111)). RESULTS: Phantom studies showed that hot rods separated by 0.35 mm can be distinguished and that 0.65-mm-diameter cold rods can be visualized, both at low-counting-rate acquisitions (111 and 59 MBq x h, respectively). In both mouse studies, the SPECT images allowed a clear delineation of the radioactivity concentrated over the cortex area of the kidneys, whereas the pelvis and the pelviureteral junction (1 mm) appeared as cold areas. The quantitative data derived from SPECT were in good agreement with the radioactivity counting obtained with a gamma-counter after isolation of the kidneys. In addition, in the mouse injected with (111)In-pentetreotide, the kidney radioactivity distribution seen with SPECT was in agreement with the ex vivo autoradiograms of the isolated kidneys. CONCLUSION: The phantom studies showed a clear improvement of the spatial resolution over the results reported in the literature with other dedicated small-animal SPECT systems, especially in cold-rod phantom studies. The increased performance can be ascribed to the high stability of the system with regard to the statistical noise present in the acquired data. The mouse studies showed that this system will be most useful for in vivo high-resolution SPECT and quantitative biodistribution studies in rodents, even with medium-energy radioisotopes that are difficult to image, such as (111)In

Megalin is essential for renal proximal tubule reabsorption of In-111-DTPA-octreotide

Radiolabeled somatostatin analogs have been shown to be important radiopharmaceuticals for tumor diagnosis and radionuclide therapy. The kidney has appeared to be the critical organ during radionuclide therapy because of peptide reabsorption and retention in the proximal tubules after glomerular filtration. The molecular mechanism of renal reabsorption of these analogs has not been clarified. A possible receptor candidate is megalin, a multiligand scavenger receptor in the renal proximal tubules. The objective of this study was to investigate the role of megalin in tubular reabsorption of radiolabeled somatostatin analogs by using kidney-specific megalin-deficient mice versus mice with normal renal megalin expression. [In-111-Diethylenetriamine-pentaacetic acid (DTPA)]octreotide was used as a practical model of peptide. Methods: Renal uptake of [In-111-DTPA]octreotide was determined by animal SPECT scintigraphy at different time points after injection of the tracer and by measurement of radioactivity after isolation of the organs. Furthermore, ex vivo autoradiography of renal sections revealed the zonal distribution of radioactivity in the megalin-deficient and megalin-expressing kidneys. Results: SPECT scintigraphy of [In-111-DTPA]octreotide at 3 and 24 h after injection clearly showed lower renal radioactivity in megalin-deficient kidneys than in megalin-expressing kidneys, both in male and in female mice, in accordance with counts obtained after isolation of the organ (70%-85% reduction of uptake in the megalin-deficient kidneys, P < 0.001). Renal uptake of [In-111-DTPA]octreotide was significantly higher in female than in male kidneys (P < 0.001). Ex vivo autoradiograms clearly showed that renal radioactivity was not homogeneously distributed in the megalin-expressing kidneys but localized in the renal cortex. Quantification of the autoradiogram data confirmed the reduced radioactivity in the renal cortex of megalin-deficient kidneys. Conclusion: This study revealed the molecular mechanism of [(111)InDTPA]octreotide uptake in renal proximal tubules involving the receptor megalin. Identification of megalin may be crucial for further research into strategies to reduce renal uptake

Long-term follow-up of renal function after peptide receptor radiation therapy with Y-90-DOTA(0),Tyr (3)-octreotide and Lu-117-DOTA(0), Tyr(3)-Octreotate

The kidneys are critical organs in peptide receptor radiation therapy (PRRT). Renal function loss may become apparent many years after PRRT. We analyzed the time course of decline in creatinine clearance (CLR) in patients during a follow-up of at least 18 mo after the start of PRRT with Y-90-1,4,7,10-tetraazacyclododecane-N,N',N',N'"-tetraacetic acid (DOTA),Tyr(3)-octreotide (Y-90-DOTATOC) or Lu-177-DOTA(0),Tyr(3)-octreotate (Lu-177-DOTATATE). Methods: Twenty-eight patients with metastasized neuroendocrine tumors received 1-5 cycles of 90Y-DOTATOC, leading to renal radiation doses of 5.9-26.9 Gy per cycle and a total of 18.3-38.7 Gy. Median follow-up was 2.9 y (range, 1.5-5.4 y), with a median of 16 measurements (range, 5-53) per patient. Thirty-seven patients with metastasized neuroendocrine tumors received 3-7 cycles of 177Lu-DOTATATE, leading to renal radiation doses of 1.8-7.8 Gy per cycle and a total of 7.3-26.7 Gy. Median follow-up was 2.4 y (range, 1.7-4.0 y), with a median of 10 (range, 6-27) measurements per patient. All renal dose estimates were calculated with the MIRDOSE3 model. All patients were infused with renoprotective amino acids during the administration of the radioactive peptides. The time trend of CLR was determined by fitting a monoexponential function through the data of individual patients, yielding the decline in CLR in terms of percentage change per year. Results: The median decline in CLR was 7.3% per y in patients treated with Y-90-DOTATOC and 3.8% per y in patients treated with Lu-177-DOTATATE (P = 0.06). The time trend of decline in CLR was sustained during the follow-up period. Eleven patients had a >15% per y decline in CLR. Cumulative renal radiation dose, per-cycle renal radiation dose, age, hypertension, and diabetes are probable contributing factors to the rate of decline in CLR after PRRT. Conclusion: This study showed that the time course of CLR after PRRT was compatible with the pattern of sustained CLR loss in progressive chronic kidney disease

Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0),Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate.

The kidneys are critical organs in peptide receptor radiation therapy (PRRT). Renal function loss may become apparent many years after PRRT. We analyzed the time course of decline in creatinine clearance (CLR) in patients during a follow-up of at least 18 mo after the start of PRRT with (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA),Tyr(3)-octreotide ((90)Y-DOTATOC) or (177)Lu-DOTA(0),Tyr(3)-octreotate ((177)Lu-DOTATATE). METHODS: Twenty-eight patients with metastasized neuroendocrine tumors received 1-5 cycles of (90)Y-DOTATOC, leading to renal radiation doses of 5.9-26.9 Gy per cycle and a total of 18.3-38.7 Gy. Median follow-up was 2.9 y (range, 1.5-5.4 y), with a median of 16 measurements (range, 5-53) per patient. Thirty-seven patients with metastasized neuroendocrine tumors received 3-7 cycles of (177)Lu-DOTATATE, leading to renal radiation doses of 1.8-7.8 Gy per cycle and a total of 7.3-26.7 Gy. Median follow-up was 2.4 y (range, 1.7-4.0 y), with a median of 10 (range, 6-27) measurements per patient. All renal dose estimates were calculated with the MIRDOSE3 model. All patients were infused with renoprotective amino acids during the administration of the radioactive peptides. The time trend of CLR was determined by fitting a monoexponential function through the data of individual patients, yielding the decline in CLR in terms of percentage change per year. RESULTS: The median decline in CLR was 7.3% per y in patients treated with (90)Y-DOTATOC and 3.8% per y in patients treated with (177)Lu-DOTATATE (P = 0.06). The time trend of decline in CLR was sustained during the follow-up period. Eleven patients had a >15% per y decline in CLR. Cumulative renal radiation dose, per-cycle renal radiation dose, age, hypertension, and diabetes are probable contributing factors to the rate of decline in CLR after PRRT. CONCLUSION: This study showed that the time course of CLR after PRRT was compatible with the pattern of sustained CLR loss in progressive chronic kidney disease

Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0),Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate.

The kidneys are critical organs in peptide receptor radiation therapy (PRRT). Renal function loss may become apparent many years after PRRT. We analyzed the time course of decline in creatinine clearance (CLR) in patients during a follow-up of at least 18 mo after the start of PRRT with (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA),Tyr(3)-octreotide ((90)Y-DOTATOC) or (177)Lu-DOTA(0),Tyr(3)-octreotate ((177)Lu-DOTATATE). METHODS: Twenty-eight patients with metastasized neuroendocrine tumors received 1-5 cycles of (90)Y-DOTATOC, leading to renal radiation doses of 5.9-26.9 Gy per cycle and a total of 18.3-38.7 Gy. Median follow-up was 2.9 y (range, 1.5-5.4 y), with a median of 16 measurements (range, 5-53) per patient. Thirty-seven patients with metastasized neuroendocrine tumors received 3-7 cycles of (177)Lu-DOTATATE, leading to renal radiation doses of 1.8-7.8 Gy per cycle and a total of 7.3-26.7 Gy. Median follow-up was 2.4 y (range, 1.7-4.0 y), with a median of 10 (range, 6-27) measurements per patient. All renal dose estimates were calculated with the MIRDOSE3 model. All patients were infused with renoprotective amino acids during the administration of the radioactive peptides. The time trend of CLR was determined by fitting a monoexponential function through the data of individual patients, yielding the decline in CLR in terms of percentage change per year. RESULTS: The median decline in CLR was 7.3% per y in patients treated with (90)Y-DOTATOC and 3.8% per y in patients treated with (177)Lu-DOTATATE (P = 0.06). The time trend of decline in CLR was sustained during the follow-up period. Eleven patients had a >15% per y decline in CLR. Cumulative renal radiation dose, per-cycle renal radiation dose, age, hypertension, and diabetes are probable contributing factors to the rate of decline in CLR after PRRT. CONCLUSION: This study showed that the time course of CLR after PRRT was compatible with the pattern of sustained CLR loss in progressive chronic kidney disease