lutetium

Accuracy of absorbed dose calculations in personalized internal radionuclide therapy is directly related to the accuracy of the activity (or activity concentration) estimates obtained at each of the imaging time points. MIRD Pamphlet No. 23 presented a general overview of methods that are required for quantitative SPECT imaging. The present document is next in a series of isotope-specific guidelines and recommendations that follow the general information that was provided in MIRD 23. This paper focuses on 177-Lu (Lutetium) and its main application in radiopharmaceutical therapy.

Accuracy of absorbed dose calculations in personalized internal radionuclide therapy is directly related to the accuracy of the activity (or activity concentration) estimates obtained at each of the imaging time points. MIRD Pamphlet No. 23 presented a general overview of methods that are required for quantitative SPECT imaging. The present document is next in a series of isotope-specific guidelines and recommendations that follow the general information that was provided in MIRD 23. This paper focuses on 177-Lu (Lutetium) and its main application in radiopharmaceutical therapy.

UNLABELLED Gastrin-releasing peptide receptors (GRP-R) are upregulated in many cancers, including prostate, breast, and lung. We describe a new radiolabeled bombesin (BBN) analog for imaging and systemic radiotherapy that has improved pharmacokinetics (PK) and better retention of radioactivity in the tumor. METHODS DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA) was synthesized and radiolabeled. The human prostate cancer cell line PC-3 was used to determine the binding (Kd), retention, and efflux of 177Lu-AMBA. Receptor specificity was determined by in vitro autoradiography in human tissues. PK and radiotherapy studies were performed in PC-3 tumor-bearing male nude mice. RESULTS 177Lu-AMBA has a high affinity for the GRP-R (Kd, 1.02 nmol/L), with a maximum binding capacity (Bmax) of 414 fmol/10(6) cells (2.5 x 10(5) GRP-R/cell). Internalization was similar for 177Lu-AMBA (76.8%), 177Lu-BBN8 (72.9%), and 125I-[Tyr4]-BBN (74.9%). Efflux was markedly lower for 177Lu-AMBA (2.9%) ...

Gastrin-releasing peptide receptors (GRP-R) are upregulated in many cancers, including prostate, breast, and lung. We describe a new radiolabeled bombesin (BBN) analog for imaging and systemic radiotherapy that has improved pharmacokinetics (PK) and better retention of radioactivity in the tumor.

Kanamycin is an antibiotic, isolated from Streptomyces kanamyceticus, which is used to treat serious bacterial infections. The fact that the present radioligand (99m) Tc-kanamycin used for diagnosis is short-lived, raised a need to label and study kanamycin with one of the most important beta (β) radiation emitting isotope (177) Lu. Labeling yield of (177) Lu-kanamycin was confirmed by different chromatography techniques such as paper chromatography, TLC, HPLC. Several experiments were performed to optimize labeling with changing reaction conditions such as pH, temperature, amount of ligand, and reaction time etc. In vitro stability analysis was performed incubation with human serum. Electrophoresis analysis was also conducted to determine the charge on (177) Lu-kanamycin. The biodistribution and scintigraphy were performed in normal mice and rabbit, respectively, at different time intervals of post injection.(177) Lu-kanamycin was prepared with very high yield (~100%), with excellent stability in vivo and in vitro (>99% 6h post-prep.), at pH 7. Maximum labeling was achieved at less reaction time (15 min), with maximum conjugation of the ligand (12.5 mg) with (177) Lu. Electrophoresis analysis showed net neutral charge. The radioligand showed rapid clearance from body in biodistribution and scintigraphy studies. The preparation (177) Lu-kanamycin could be used as a radio-pharmaceutical for imaging purpose, especially when transporting the radioligand to long-range distances. This article is protected by copyright. All rights reserved.

Kanamycin is an antibiotic, isolated from Streptomyces kanamyceticus, which is used to treat serious bacterial infections. The fact that the present radioligand (99m) Tc-kanamycin used for diagnosis is short-lived, raised a need to label and study kanamycin with one of the most important beta (β) radiation emitting isotope (177) Lu. Labeling yield of (177) Lu-kanamycin was confirmed by different chromatography techniques such as paper chromatography, TLC, HPLC. Several experiments were performed to optimize labeling with changing reaction conditions such as pH, temperature, amount of ligand, and reaction time etc. In vitro stability analysis was performed incubation with human serum. Electrophoresis analysis was also conducted to determine the charge on (177) Lu-kanamycin. The biodistribution and scintigraphy were performed in normal mice and rabbit, respectively, at different time intervals of post injection.(177) Lu-kanamycin was prepared with very high yield (~100%), with excellent stability in vivo and in vitro (>99% 6h post-prep.), at pH 7. Maximum labeling was achieved at less reaction time (15 min), with maximum conjugation of the ligand (12.5 mg) with (177) Lu. Electrophoresis analysis showed net neutral charge. The radioligand showed rapid clearance from body in biodistribution and scintigraphy studies. The preparation (177) Lu-kanamycin could be used as a radio-pharmaceutical for imaging purpose, especially when transporting the radioligand to long-range distances. This article is protected by copyright. All rights reserved.

Integrin αvβ3 plays a significant role in angiogenesis during tumor growth and metastasis, and is a receptor for the extracellular matrix proteins with the exposed arginine(R)-glycine(G)-aspartic acid(D) tripeptide sequence. The over-expression of integrin αvβ3 during tumor growth and metastasis presents an interesting molecular target for both early detection and treatment of rapidly growing solid tumors. Considering the advantages of (177)Lu for targeted radiotherapy and enhanced tumor targeting capability of cyclic RGD peptide dimer, an attempt has been made to optimize the protocol for the preparation of clinical dose of (177)Lu labeled DOTA-E[c(RGDfK)]2 (E=Glutamic acid, f=phenyl alanine, K=lysine) as a potential agent for targeted tumor therapy. (177)Lu was produced by thermal neutron bombardment on enriched Lu2O3 (82% in (176)Lu) target at a flux of 1 × 10(14) n/cm(2).s for 21 d. Therapeutic dose of (177)Lu-DOTA-E[c(RGDfK)]2 (7.4GBq) was prepared by adding the aqueous solutio...

177Lu (T 1/2 = 6.71 d, Ebeta(max) = 497 keV) has radionuclidic properties suitable for use in palliative therapy of bone pain due to metastasis. 177Lu was produced in high-specific activity (3-4TBq/g) and excellent radionuclidic purity (100%) by thermal neutron bombardment of natural Lu target. Two cyclic tetraaminomethylene phosphonate ligands, namely DOTMP and CTMP were synthesized and radiolabeled with 177Lu. The 177Lu-DOTMP complex was formed with very high yield (> 99%) and showed excellent stability (up to 40 d at room temperature). Biodistribution of 177Lu-DOTMP was carried out in Wistar rats and the complex showed significant bone uptake (4.23%/g in femur and 5.23% in tibia at 3 h p. i.), rapid clearance from blood (no activity at 3 h p. i.) and minimum uptake in soft tissues.

The purpose of this study was to quantify the influence of outside field of view (FOV) activity concentration (Ac,out) on the noise equivalent count rate (NECR), scatter fraction (SF) and image quality of a 3D LSO whole-body PET/CT scanner. The contrast-to-noise ratio (CNR) was the figure of merit used to characterize the image quality of PET scans. A modified International

The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an average number of 4.9 ± 1.1 DOTA per Rituximab molecule. Labeling with 177Lu was performed in high specific activity with great in vitro stability. Biodistribution in healthy and xenographed mice showed tumor uptake and high in vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA-Rituximab prepared from DOTA-NHS-ester suggest the potential for the application of the 177Lu-labeled antibody in preliminary clinical studies.

UNLABELLED The therapeutic effects of peptide receptor-based radionuclide therapy are extensively being investigated in rats bearing tumors. Both the dose to the tumor and the therapy-limiting dose to normal tissues, such as kidneys and bone marrow, are of interest for these preclinical studies. The aim of this work was to develop a generalized computational model for internal dosimetry in rats. METHODS Mature rats were dissected and the relative positions, dimensions, and weights of all of their major organs were measured. A mathematic model was set up for the rat body and its internal organs to enable Monte Carlo radiation transport calculations to determine estimates for both tumor and organ self-doses as cross-organ doses for (90)Y, (111)In, and (177)Lu. The organs and body were mostly of ellipsoid shape with the axes given as the measured length, width, and height normalized to values that, together with the measured weights, are consistent with the recommended soft-tissue and ...

Therapeutic efficacy in radioimmunotherapy depends, among other things, on the choice of the radionuclide. The aim of the present study was to determine the most suitable radionuclide for radioimmunotherapy with monoclonal antibody MN-14 to carcinoembryonic antigen in an experimental model of small peritoneal metastases of colorectal origin. In nude mice with intraperitoneal LS174T tumors (diameter, 1-3 mm), the biodistributions of MN-14 labeled with (131)I ((131)I-MN-14), (186)Re-mercaptoacetyltriglycine ((186)Re-MN-14), and (88)Y-diethylenetriaminepentaacetic acid (DTPA) ((88)Y-MN-14) after intravenous and intraperitoneal administration were determined. Subsequently, the therapeutic efficacies of equally toxic activity doses of (131)I-MN-14 (9.25 MBq per mouse), (186)Re-MN-14 (9.25 MBq per mouse), (90)Y-MN-14 (3.15 MBq per mouse), and MN-14 labeled with (177)Lu-DTPA ((177)Lu-MN-14) (8.33 MBq per mouse) after intraperitoneal administration were determined. Each of the radioimmunoco...