Influence of route of administration on [ 3 H]-camptothecin distribution and tumor uptake in CASE-bearing nude mice: whole-body autoradiographic studies

1996 ◽  
Vol 39 (1-2) ◽  
pp. 122-130 ◽  
Author(s):  
A. E. Ahmed ◽  
Sam Jacob ◽  
Beppino C. Giovanella ◽  
Anthony J. Kozielski ◽  
John S. Stehlin Jr. ◽  
...  
Keyword(s):  
Nude Mice ◽  
Route Of Administration ◽  
Whole Body ◽  
Tumor Uptake

Evaluation of a New 99mTc-labeled GnRH Analogue as a Possible Imaging Agent for Prostate Cancer Detection

2020 ◽  
Vol 20 (14) ◽  
pp. 1695-1703
Author(s):  
Arezou Masteri Farahani ◽  
Fariba Maleki ◽  
Nourollah Sadeghzadeh ◽  
Saeid Abediankenari ◽  
Seyed Mohammad Abedi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Nude Mice ◽  
Normal Saline ◽  
Radiochemical Purity ◽  
Prostate Cancer Cell ◽  
Gnrh Analogue ◽  
Tumor Uptake ◽  
Prostate Cancer Cell Lines

Introduction: Prostate cancer is a serious threat to men’s health so it is necessary to develop technics for early detection of this malignancy. The purpose of this research was the evaluation of a new99mTc-labeled GnRH analogue as an imaging probe for tumor targeting of prostate cancer. Methods: 99mTc-labeled-DLys6-GnRH analogue was prepared based on HYNIC as a chelating agent and tricine/ EDDA as coligands for labeling with 99mTc. HYNIC was coupled to epsilon amino group of DLys6 through aminobutyric acid (GABA) as a linker. Radiochemical purity and stability in normal saline and serum, were determined by TLC and HPLC methods. Furthermore, calculation of protein-binding and partition coefficient constant were carried out for 99mTc labeled peptide. The cellular experiments including receptor binding specificity and affinity were studied using three prostate cancer cell lines LN-CaP, DU-145 and PC-3. Finally, the animal assessment and SPECT imaging of radiolabeled GnRH analogue were evaluated on normal mice and nude mice bearing LN-CaP tumor. Results: The GnRH conjugate was labeled with high radiochemical purity (~97%). The radiolabeled peptide showed efficient stability in the presence of normal saline and human serum. The in vitro cellular assays on three prostate cancer cell lines indicated that the radiotracer was bound to LN-CaP cells with higher affinity compared to DU-145 and PC-3 cells. The Kd values of 99mTc- HYNIC (tricine/ EDDA)-Gaba-D-Lys6GnRH were 89.39±26.71, 93.57±30.49 and107.3±18.82 in LN-CaP, PC-3 and DU-145 cells respectively. The biodistribution studies in normal mice and LN-CaP tumor-bearing nude mice showed similar results including rapid blood clearance and low radioactivity accumulation in non-target organs. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor uptake was 1.72±0.45 %ID/g at 1h p.i. decreasing to 0.70±0.06%ID/g at 4h p.i. for 99mTc-HYNIC-Gaba-D-Lys6GnRH. The maximum tumor/ muscle ratio was 2.30 at 1h p.i. Pre-saturation of receptor using an excess of unlabeled peptide revealed that the tumor uptake was receptor mediated. The results of the SPECT image of LN-CaP tumor were in agreement with the biodistribution data. Conclusion: Based on this study, we suggest LN-CaP as a favorable cell line for in vivo studies on GnRH analogues. Moreover, this report shows that 99mTc-HYNIC (tricine/EDDA)-Gaba-D-Lys6GnRH may be a suitable candidate for further evaluation of prostate cancer.

scholarly journals 89Zr anti-CD44 immuno-PET monitors  CD44 expression on splenic myeloid cells and HT29 colon cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Won Park ◽  
Kyung-Ho Jung ◽  
Jin Hee Lee ◽  
Seung Hwan Moon ◽  
Young Seok Cho ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Nude Mice ◽  
Myeloid Cells ◽  
Human Antibody ◽  
Tumor Uptake ◽  
Colon Cancer Cells ◽  
Cell Surface Glycoprotein ◽  
Cd44 Expression ◽  
Human And Mouse

AbstractCD44 is a cell-surface glycoprotein involved in cell–cell interaction, adhesion, and migration. CD44 is found on colon cancer cells and on immune cells. Previous studies of 89Zr PET imaging of CD44 have relied on an anti-human antibody (Ab), which can influence biodistribution in murine models. In this study, we used an Ab that cross-reacts with both human and mouse origin CD44 of all isoforms to unveil the type of leukocyte responsible for high splenic anti-CD44 uptake and investigate how its regulation can influence tumor immuno-PET. The Ab was site-specifically labeled with 89Zr-deferoxamine on cysteine residues. 89Zr-anti-CD44 demonstrated high-specific binding to HT29 human colon cancer cells and monocytic cells that showed CD44 expression. When 89Zr-anti-CD44 was administered to Balb/C nude mice, there was remarkably high splenic uptake but low SNU-C5 tumor uptake (1.2 ± 0.7%ID/g). Among cells isolated from Balb/C mouse spleen, there was greater CD44 expression on CD11b positive myeloid cells than lymphocytes. In cultured monocytic and macrophage cells, LPS stimulation upregulated CD44 expression and increased 89Zr-anti-CD44 binding. Similarly, normal Balb/C mice that underwent lipopolysaccharide (LPS) stimulation showed a significant upregulation of CD44 expression on splenic myeloid cells. Furthermore, LPS treatment stimulated a 2.44-fold increase of 89Zr-anti-CD44 accumulation in the spleen, which was attributable to splenic myeloid cells. Finally, in Balb/C nude mice bearing HT29 tumors, we injected 89Zr-anti-CD44 with greater Ab doses to reduce binding to splenic cells. The results showed lower spleen uptake and improved tumor uptake (2.9 ± 1.3%ID/g) with a total of 300 μg of Ab dose, and further reduction of spleen uptake and greater tumor uptake (5.7 ± 0.0%ID/g) with 700 μg Ab dose. Thus, using an 89Zr labeled Ab that cross-reacts with both human and mouse CD44, we demonstrate that CD44 immuno-PET has the capacity to monitor CD44 regulation on splenic myeloid cells and may also be useful for imaging colon tumors.

Abstract 2677: Determination of the optimal route of administration ofSalmonella typhimuriumA1-R to target breast cancer in nude mice

2012 ◽  
Author(s):  
Yong Zhang ◽  
Atsushi Suetsugu ◽  
Nan Zhang ◽  
Lei Zhang ◽  
Robert M. Hoffman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nude Mice ◽  
Route Of Administration ◽  
Optimal Route

scholarly journals Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177Lutetium

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 348 ◽  
Author(s):  
Kevin J. H. Allen ◽  
Rubin Jiao ◽  
Mackenzie E. Malo ◽  
Connor Frank ◽  
Darrell R. Fisher ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Ct Imaging ◽  
Whole Body ◽  
Tumor Uptake ◽  
Slowing Down ◽  
Humanized Antibody ◽  
Alpha Emitter ◽  
Systemic Side Effects ◽  
High Tumor Uptake ◽  
Dosimetry Data

Melanoma is a cancer with increasing incidence and there is a need for alternatives to immunotherapy within effective approaches to treatment of metastatic melanoma. We performed comparative radioimmunotherapy (RIT) of experimental B16-F10 melanoma with novel humanized IgG to melanin h8C3 labeled with a beta emitter, 177Lu, and an alpha-emitter, 213Bi, as well as biodistribution, microSPECT/CT imaging, and mouse and human dosimetry calculations. microSPECT/CT imaging showed that a humanized antibody that targets “free” melanin in the tumor microenvironment had high tumor uptake in B16F10 murine melanoma in C57Bl/6 mice, with little to no uptake in naturally melanized tissues. Extrapolation of the mouse dosimetry data to an adult human demonstrated that doses delivered to major organs and the whole body by 177Lu-h8C3 would be approximately two times higher than those delivered by 213Bi-h8C3, while the doses to the tumor would be almost similar. RIT results indicated that 213Bi-h8C3 was more effective in slowing down the tumor growth than 177Lu-h8C3, while both radiolabeled antibodies did not produce significant hematologic or systemic side effects. We concluded that h8C3 antibody labeled with 213Bi is a promising reagent for translation into a clinical trial in patients with metastatic melanoma.

scholarly journals Down-Regulation of Toll-Like Receptor 5 (TLR5) Increased VEGFR Expression in Triple Negative Breast Cancer (TNBC) Based on Radionuclide Imaging

2021 ◽  
Vol 11 ◽  
Author(s):  
Wen Jiang ◽  
Yeming Han ◽  
Ting Liang ◽  
Chao Zhang ◽  
Feng Gao ◽  
...  
Keyword(s):  
Triple Negative ◽  
Whole Body ◽  
Tumor Uptake ◽  
Toll Like Receptor ◽  
Rt Pcr ◽  
Down Regulation ◽  
Tumor Bearing ◽  
4T1 Cells ◽  
Toll Like Receptor 5 ◽  
Tlr5 Expression

In this study, GFP-tagged TNBC 4T1 cells with down-regulated TLR5 expression (TLR5− 4T1) and normal TLR5 expression (TLR5+ 4T1) were constructed, respectively. RT-PCR and Western blot studies showed that down-regulation of TLR5 obviously increased the expression of VEGFR in 4T1 cells. Highly stable radio-probes 125I-anti-TLR5 mAb/125I-VEGF/125I-IgG were obtained with labeling rates over 85% and radiochemical purities above 90%. Among these three probes, 125I−anti−TLR5 mAb and 125I-VEGF were used for specifically imaging TNBC, while 125I-IgG was used for comparison. Whole-body phosphorus autoradiography showed clear imaging at 48 h after injection of 125I-anti-TLR5 mAb and 125I-VEGF also provided clear imaging at 24 h. Biodistribution study demonstrated a higher tumor uptake of 125I-anti-TLR5 mAb in TLR5+ group compared with that in TLR5− group (P < 0.05), whereas tumor uptake of 125I-VEGF in TLR5+ group was lower than that in the TLR5− group (P < 0.05). Immunohistochemical staining suggested that the expression of TLR5 was lower, whereas the expression of VEGFR, CD31, and MVD (microvessel density) was higher in TLR5− tumor-bearing mice. In summary, the down-regulation of TLR5 in TNBC promoted the VEGFR expression and angiogenesis, resulting in the proliferation of TNBC cells. TLR5/VEGF might be a better indicator for monitoring the development of TNBC.

Enhancement of Tumor Contrast on Radioimmunoscans by Using Mixtures of Monoclonal Antibody F(ab’)2 Fragments

1986 ◽  
Vol 25 (06) ◽  
pp. 216-219 ◽  
Author(s):  
A. Alavi ◽  
H. Koprowski ◽  
D. Herlyn ◽  
D. L. Munz
Keyword(s):  
Monoclonal Antibody ◽  
Gastrointestinal Tract ◽  
Nude Mice ◽  
Half Life ◽  
The Body ◽  
Whole Body ◽  
Antigenic Determinants ◽  
Body Images ◽  
Biological Half Life ◽  
Adenocarcinoma Cells

F(ab’)2 fragments of MAbs GA 73-3 (IgG 2a) and CO 29.11 (IgG 1), which detect distinct antigenic determinants on adenocarcinoma cells of the gastrointestinal tract, were labeled with 131I using the iodogen method. 41 nude mice bearing SW-948 CRC tumors were injected either with a mixture of 100 ¼Ci (11 ¼g) each (n = 9) of the two 131l-F(ab’)2 fragments or with either fragment alone at various doses (each group consisting of 8 mice): GA 73-3,100 ¼Ci (11 ¼g) and 200 ¼Ci (25 ¼g); CO 29.11,100 ¼Ci (11 ¼g) and 200 ¼Ci (26 ¼g). Whole-body images of the mice were obtained daily for up to six days after injection. Ratios of cpm/pixel in the tumor to those in the rest of the body (rob), representing tumor contrast, were significantly (p <0.05) higher in the group of mice injected with the mixture (3.9 ± 1.5) as compared to those given 100 or 200 jiCi of either fragment separately. The biological half-life (T1/2 biol) of the mixture (44.7 ± 14.5 h) in the CRC tumors was significantly (p <0.05) longer than T1/2 biol determined in the groups given either fragment alone. Tv bioL in the rob was similar in all groups of mice examined.

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