Mangal S Dandekar
@djsce.ac.in
Assistant Professor
SVKM's Dwarkadas J. Sanghvi College of Engineering, Mumbai 400056, India
RESEARCH INTERESTS
Cancer Research
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Jeffrey R. Tseng, Keon Wook Kang, Mangal Dandekar, Shahriar Yaghoubi, Joseph H. Lee, James G. Christensen, Stephen Muir, Patrick W. Vincent, Neil R. Michaud, and Sanjiv S. Gambhir
Society of Nuclear Medicine
The purpose of this study was to evaluate the efficacy of CE-355621, a novel antibody against c-Met, in a subcutaneous U87 MG xenograft mouse model using 18F-FDG small-animal PET. Methods: CE-355621 or control vehicle was administered intraperitoneally into nude mice (drug-treated group, n = 12; control group, n = 14) with U87 MG subcutaneous tumor xenografts. Drug efficacy was evaluated over 2 wk using 18F-FDG small-animal PET and compared with tumor volume growth curves. Results: The maximum %ID/g (percentage injected dose per gram of tissue) of 18F-FDG accumulation in mice treated with CE-355621 remained essentially unchanged over 2 wk, whereas the %ID/g of the control tumors increased 66% compared with the baseline. Significant inhibition of 18F-FDG accumulation was seen 3 d after drug treatment, which was earlier than the inhibition of tumor volume growth seen at 7 d after drug treatment. Conclusion: CE-355621 is an efficacious novel antineoplastic chemotherapeutic agent that inhibits 18F-FDG accumulation earlier than tumor volume changes in a mouse xenograft model. These results support the use of 18F-FDG PET to assess early tumor response for CE-355621.
Z. Cheng, L. Zhang, E. Graves, Z. Xiong, M. Dandekar, X. Chen, and S. S. Gambhir
Society of Nuclear Medicine
18F-Labeled small synthetic peptides have emerged as attractive probes for imaging various molecular targets with PET. The α-melanocyte-stimulating hormone (α-MSH) receptor (melanocortin type 1 receptor [MC1R]) is overexpressed in most murine and human melanomas. It is a promising molecular target for diagnosis and therapy of melanomas. However, 18F compounds have not been successfully developed for imaging the MC1R. Methods: In this study, an α-MSH analog, Ac-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH2 (NAPamide), was radiolabeled with N-succinimidyl-4-18F-fluorobenzoate (18F-SFB). The resulting radiopeptide was evaluated as a potential molecular probe for small-animal PET of melanoma and MC1R expression in melanoma xenografted mouse models. Results: The binding affinity of 19F-SFB−conjugated NAPamide, 19F-FB-NAPamide, was determined to be 7.2 ± 1.2 nM (mean ± SD) using B16/F10 cells and 125I-(Tyr2)-[Nle4,d-Phe7]-α-MSH [125I-(Tyr2)-NDP] as a radioligand. The biodistribution of 18F-FB-NAPamide was then investigated in C57BL/6 mice bearing subcutaneous murine B16/F10 melanoma tumors with high expression of MC1Rs and Fox Chase Scid mice bearing human A375M melanoma with a relatively low number of MC1R receptors. Biodistribution experiments showed that tumor uptake values (percentage injected dose per gram of tumor [%ID/g]) of 18F-FB-NAPamide were 1.19 ± 0.11 %ID/g and 0.46 ± 0.11 %ID/g, in B16/F10 and A375M xenografted melanoma at 1 h after injection, respectively. Furthermore, the B16/F10 tumor uptake was significantly inhibited by coinjection with excess α-MSH peptide (P < 0.05), indicating that 18F-FB-NAPamide specifically recognizes the MC1R in living mice. Small-animal PET of 18F-FB-NAPamide in mice bearing B16/F10 and A375M tumors at 1 h after tail vein injection revealed good B16/F10 tumor-to-background contrast and low A375M tumor-to-background ratios. Conclusion: 18F-FB-NAPamide is a promising molecular probe for α-MSH receptor-positive melanoma PET and warrants further study.
M. Dandekar, J. R. Tseng, and S. S. Gambhir
Society of Nuclear Medicine
18F-FDG has been used to image mouse xenograft models with small-animal PET for therapy response. However, the reproducibility of serial scans has not been determined. The purpose of this study was to determine the reproducibility of 18F-FDG small-animal PET studies. Methods: Mouse tumor xenografts were formed with B16F10 murine melanoma cells. A 7-min small-animal PET scan was performed 1 h after a 3.7- to 7.4-MBq 18F-FDG injection via the tail vein. A second small-animal PET scan was performed 6 h later after reinjection of 18F-FDG. Twenty-five sets of studies were performed. Mean injected dose per gram (%ID/g) values were calculated from tumor regions of interest. The coefficient of variation (COV) from studies performed on the same day was calculated to determine the reproducibility. Activity from the second scans performed after 6 h were adjusted by subtracting the estimated residual activity from the first 18F-FDG injection. For 7 datasets, an additional scan immediately before the second injection was performed, and residual activity from this additional delayed scan was subtracted from the activity of the second injection. COVs of both subtraction methods were compared. Blood glucose values were measured at the time of injection and used to correct the %ID/g values. Results: The COV for the mean %ID/g between 18F-FDG small-animal PET scans performed on the same day 6 h apart was 15.4% ± 12.6%. The delayed scan subtraction method did not produce any significant change in the COV. Blood glucose correction increased the COV. The injected dose, tumor size, and body weight did not appear to contribute to the variability of the scans. Conclusion: 18F-FDG small-animal PET mouse xenograft studies were reproducible with moderately low variability. Therefore, serial small-animal PET studies may be performed with reasonable accuracy to measure tumor response to therapy.