For imaging of dopamine D2/3 receptors, agonist tracers are favoured over antagonists because they are more sensitive to detection of dopamine release and because they may selectively label the high-affinity receptor state. We have developed novel D2/3 receptor selective agonists that can be radiolabelled with [123I], which label is advantageous over most other labels, such as carbon-11, as it has a longer half-life. Particularly, we considered (R) N-[7-hydroxychroman-2-yl]-methyl 4-iodobenzyl amine (compound 1) as an attractive candidate for development as it shows high binding affinity to D2/3 receptors in vitro, and here we report on the characterization of this first [123I]-labelled D2/3 receptor agonist radiopharmaceutical intended for SPECT imaging. The appropriate tin precursor for [123I]-1 was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30&#x2013;35&#x25;) and a good purity (&#x3e;95&#x25;) for [123I]-1. In biodistribution experiments in Wistar rats intravenous injection of [123I]-1 resulted in a fast brain uptake, where the observed binding in the D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30&#x2009;min to 4&#x2009;h p.i. Storage phosphor imaging experiments, however, did not show specific D2/3 receptor binding. In conclusion, despite promising in vitro data for 1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [123I]-1.

Jan-Peter van Wieringen

Kora de Bruin

Henk M. Janssen

P. Michel Fransen

Anton G. M. Janssen

Peter A. van Doremalen

Martin C. Michel

Philip H. Elsinga

Jan Booij

Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a Potential Agonist Ligand for SPECT Imaging of Dopamine D2/3 Receptors

Tc-Tetrofosmin (Tc-TF) and Tc-Sestamibi (Tc-MIBI) are SPECT tracers that have been used for brain tumor imaging. Tumor&#x2019;s multidrug resistance phenotype, namely, P-glycoprotein (p-gp), and the multidrug resistance related proteins (MRPs) expression have been suggested to influence both tracers&#x2019; uptake. In the present study we set out to compare Tc-MIBI uptake in high-grade glioma cell lines and to investigate the influence of gliomas p-gp expression on both tracers&#x2019; uptake. We used four glioma cell lines (U251MG, A172, U87MG, and T98G). The expression of p-gp protein was evaluated by flow cytometry. Twenty &#x3BC;Ci (7.4&#x000B7;105&#x2009;Bq) of Tc-TF and Tc-MIBI were used. The radioactivity in the cellular lysate was measured with a dose calibrator. P-gp was significantly expressed only in the U251MG cell line (). In all gliomas cell lines (U251MG, U87MG, A172, and T98G) the Tc-TF uptake was significantly higher than Tc-sestamibi. The U251MG cell line, in which significant p-gp expression was documented, exhibited the strongest uptake difference. Tc-TF uptake was higher than Tc-MIBI in all studied high-grade glioma cell lines. Thus, Tc-TF may be superior to Tc-MIBI for glioma imaging in vivo.

George A. Alexiou

Xanthi Xourgia

Evrysthenis Vartholomatos

Spyridon Tsiouris

John A. Kalef-Ezra

Andreas D. Fotopoulos

Athanasios P. Kyritsis

Comparison of 99mTc-Tetrofosmin and 99mTc-Sestamibi Uptake in Glioma Cell Lines: The Role of P-Glycoprotein Expression

Yared Tekabe

Maria Kollaros

Qing Li

Geping Zhang

Chong Li

Ann Marie Schmidt

Lynne L. Johnson

Beneficial Effect of Glucose Control on Atherosclerosis Progression in Diabetic ApoE&#x2212;/&#x2212; Mice: Shown by Rage Directed Imaging

Rapid developments in the field of medical imaging have opened new avenues for the use of positron emitting labeled microparticles. The radioisotope used in our research was 68Ga, which is easy to obtain from a generator and has good nuclear properties for PET imaging. Methods. Commercially available macroaggregated albumin (MAA) microparticles were suspended in sterile saline, centrifuged to remove the free albumin and stannous chloride, relyophilized, and stored for later labeling with 68Ga. Labeling was performed at different temperatures and times. 68Ga purification settings were also tested and optimized. Labeling yield and purity of relyophilized MAA microparticles were compared with those that were not relyophilized. Results. MAA particles kept their original size distribution after relyophilization. Labeling yield was 98&#x25; at 75&#xb0;C when a 68Ga purification system was used, compared to 80&#x25; with unpurified 68Ga. Radiochemical purity was over 97&#x25; up to 4 hours after the labeling. The relyophilized MAA and labeling method eliminate the need for centrifugation purification of the final product and simplify the labeling process. Animal experiments demonstrated the high in vivo stability of the obtained PET agent with more than 95&#x25; of the activity remaining in the lungs after 4 hours.

Alejandro Amor-Coarasa

Andrew Milera

Denny Carvajal

Seza Gulec

Anthony J. McGoron

Lyophilized Kit for the Preparation of the PET Perfusion Agent [68Ga]-MAA

Metastatic spread is the leading cause of death from cancer. Early detection of cancer at primary and metastatic sites by noninvasive imaging modalities would be beneficial for both therapeutic intervention and disease management. Noninvasive imaging modalities such as bioluminescence (optical), positron emission tomography (PET)/X-ray computed tomography (CT), and magnetic resonance imaging (MRI) can provide complementary information and accurately measure tumor growth as confirmed by histopathology. Methods. We validated two metastatic tumor models, MDA-MD-231-Luc and B16-F10-Luc intravenously injected, and 4T1-Luc cells orthotopically implanted into the mammary fat pad. Longitudinal whole body bioluminescence imaging (BLI) evaluated metastasis, and tumor burden of the melanoma cell line (B16-F10-Luc) was correlated with (PET)/CT and MRI. In addition, ex vivo imaging evaluated metastasis in relevant organs and histopathological analysis was used to confirm imaging. Results. BLI revealed successful colonization of cancer cells in both metastatic tumor models over a 4-week period. Furthermore, lung metastasis of B16-F10-Luc cells imaged by PET/CT at week four showed a strong correlation (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2032003pt" id="M1" height="12.2089pt" version="1.1" viewBox="0 -12.0057 44.7051 12.2089" width="44.7051pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-83" d="M610 18C585 26 567 34 540 68C517 97 499 128 476 171C452 215 425 276 413 304C496 332 570 394 570 494C570 555 545 595 509 619S419 650 364 650H139L133 622C216 615 219 612 203 527L129 132C112 40 105 36 23 28L17 0H279L285 28C199 34 194 40 211 132L239 284H284C320 284 334 275 351 236C374 182 394 140 420 93C459 23 495 -1 592 -8H600L610 18ZM480 485C480 424 449 372 403 342C374 323 338 316 293 316H245L291 562C296 589 301 601 311 608S337 618 358 618C432 618 480 575 480 485Z"/></g><g transform="matrix(.0095,0,0,-0.0095,8.495,-5.984)"><path id="g50-51" d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"/></g><g transform="matrix(.0135,0,0,-0.0135,17.414,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.0135,0,0,-0.0135,29.152,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.0135,0,0,-0.0135,35.655,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.0135,0,0,-0.0135,38.744,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g></svg>) with histopathology. The presence and degree of metastasis as determined by imaging correlated (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.1625996pt" id="M2" height="12.1683pt" version="1.1" viewBox="0 -12.0057 44.9083 12.1683" width="44.9083pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-83"/></g><g transform="matrix(.0095,0,0,-0.0095,8.495,-5.984)"><use xlink:href="#g50-51"/></g><g transform="matrix(.0135,0,0,-0.0135,17.414,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,29.152,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,35.655,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,38.744,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g></svg>) well with histopathology findings. Conclusions. We validated two metastatic tumor models by longitudinal noninvasive imaging with good histopathology correlation.

Pavan P. Adiseshaiah

Nimit L. Patel

Lilia V. Ileva

Joseph D. Kalen

Diana C. Haines

Scott E. McNeil

Longitudinal Imaging of Cancer Cell Metastases in Two Preclinical Models: A Correlation of Noninvasive Imaging to Histopathology

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International Journal of Molecular Imaging

Table of Contents

Table of Contents: 2014

Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a Potential Agonist Ligand for SPECT Imaging of Dopamine D_2/3 Receptors

Comparison of ^99mTc-Tetrofosmin and ^99mTc-Sestamibi Uptake in Glioma Cell Lines: The Role of P-Glycoprotein Expression

Beneficial Effect of Glucose Control on Atherosclerosis Progression in Diabetic ApoE^−/− Mice: Shown by Rage Directed Imaging

Lyophilized Kit for the Preparation of the PET Perfusion Agent [⁶⁸Ga]-MAA

Longitudinal Imaging of Cancer Cell Metastases in Two Preclinical Models: A Correlation of Noninvasive Imaging to Histopathology