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Noninvasive Imaging of _vß₃ Integrin Expression Using ¹⁸F-labeled RGD-containing Glycopeptide and Positron Emission Tomography¹

Department of Nuclear Medicine, Technische Universität München, 81675 München, Germany [R. H., H-J. W., W. A. W., S. I. Z., R. S-S., M. S.]; Institute of Organic Chemistry and Biochemistry, Technische Universität München, 85747 Garching, Germany [C. M., H. K.]; and Department of Preclinical Oncology, Merck KGaA, 64271 Darmstadt, Germany [S. L. G.]

	ABSTRACT

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The _vß₃ integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. Here we describe the ¹⁸F-labeling of the RGD-containing glycopeptide cyclo(-Arg-Gly-Asp-D-Phe-Lys(sugar amino acid)-) with 4-nitrophenyl 2-[¹⁸F]fluoropropionate and the evaluation of this compound in vitro and in tumor mouse models. Binding assays with isolated immobilized _vß₃, _vß₅, and _IIbß₃ as well as in vivo studies using _vß₃-positive and -negative murine and xenotransplanted human tumors demonstrated receptor-specific binding of the radiolabeled glycopeptide yielding high tumor:background ratios (e.g., 120 min postinjection: tumor:blood, 27.5; tumor:muscle, 10.2). First imaging results using a small animal positron emission tomograph suggest that this compound is suitable for noninvasive determination of the _vß₃ integrin status and therapy monitoring.

	Introduction

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Numerous studies have shown that the integrin _vß₃ is an important receptor affecting tumor growth, local invasiveness, and metastatic potential (1) . This dimeric transmembrane glycoprotein mediates adhesion and migration of tumor cells on a variety of extracellular matrix proteins. Furthermore, _vß₃ is strongly expressed on activated endothelial cells and plays a critical role in the angiogenic process (2) . In contrast, expression of _vß₃ is weak in resting endothelial cells and most normal organ systems. Thus, inhibition of _vß₃ is currently being evaluated as a new strategy for tumor-specific anticancer therapy. Similar to several other integrins, _vß₃ recognizes the tripeptide sequence arginine-glycine-aspartic acid (RGD). The affinity of integrins toward different ligands is critically determined by the conformation of this common binding motif. Thus, the design of RGD-containing peptides with the corresponding conformation allows selective targeting of specific integrins. In previous studies (3 , 4) , we used spatial screening techniques for the development of the first _v-selective inhibitor, cyclo(-Arg-Gly-Asp-D-Phe-Val-) (5) . More recently, peptidomimetic _vß₃ antagonists have been developed (6 , 7) . Inhibition of _vß₃ function by these peptidic and nonpeptidic antagonists has been shown to inhibit tumor growth in animal studies (6, 7, 8) . Future developments of anti-_vß₃-directed therapy and translation of these encouraging experimental data to clinical studies would be greatly facilitated by noninvasive techniques that allow serial studies of _vß₃-positive tumors. In an animal model, Sipkins et al. (9) recently demonstrated that it is feasible to image _vß₃ expression using magnetic resonance imaging and antibody-coated paramagnetic liposomes.

The aim of this study was to develop a radiolabeled analogue of cyclo(-Arg-Gly-Asp-D-Phe-Val-) that is suitable for imaging of _vß₃ expression using PET.³ In addition, the feasibility of small animal PET systems for monitoring blockade of _vß₃ by specific antagonists was evaluated in living mice.

	Materials and Methods

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All organic reagents were purchased from Merck KGaA (Darmstadt, Germany), Aldrich (Steinheim, Germany), or Fluka (Neu-Ulm, Germany) and used without further purification. Human M21 and M21-L melanoma cells were kindly provided by Dr. D. A. Cheresh (Departments of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, CA). Analytical as well as preparative RP-HPLC was performed on Sykam equipment (Gilching, Germany) using a YMC-Pack J’sphere H80 (4 µm; 150 x 20 mm) column (YMC Co., Ltd., Kyoto, Japan). For radioactivity measurements, the outlet of the UV detector was connected to a well-type NaI(Tl) detector from EG&G (München, Germany).

Preparation of [¹⁸F]Galacto-RGD.
The synthesis of the Fmoc-protected SAA (7-amino-L-glycero-L-galacto-2,6-anhydro-7-deoxyheptanoic acid) and the fluorination precursor [cyclo(-Arg-Gly-Asp-D-Phe-Lys(SAA)-)] as well as the reference glycopeptide will be described elsewhere.⁴ N.c.a. [¹⁸F]fluoride (t_1/2 =109.7 min) was produced via the ¹⁸O(p,n)¹⁸F nuclear reaction by bombardment of an isotopically enriched [¹⁸O]water target with an 11 MeV proton beam using the RDS-112 cyclotron (Siemens/CTI, Knoxville, TN). The glycopeptide was labeled using n.c.a. 4-nitrophenyl 2-[¹⁸F]fluoropropionate (specific activity, approximately 70 TBq/mmol), which was prepared as described by Wester et al. (10) . Briefly, 6 µmol of cyclo(-Arg-Gly-Asp-D-Phe-Lys(SAA)-) were dissolved in 150 µl of DMSO and added to an Eppendorf cap with dried 4-nitrophenyl 2-[¹⁸F]fluoropropionate (approximately 185 MBq). After this, 30 µmol of potassium salt of 1-hydroxy-benzotriazole in 50 µl of DMSO were added and allowed to stand for 15 min at 70°C. Isolation of the ¹⁸F-labeled glycopeptide was carried out using RP-HPLC with an acetonitrile/water/0.1% trifluoroacetic acid gradient (10–50% acetonitrile in 20 min; flow rate, 10 ml/min, t_R = 11.6 min, K' = 5.1). The solvent was removed in vacuo, and the residue was dissolved in PBS (pH 7.4) to obtain solutions that were ready for use in animal experiments.

Biological Assay.
Purification of the proteins and the isolated integrin binding assay have been described elsewhere (11) . The inhibitory capacities of [¹⁹F]Galacto-RGD were quantified by measuring its effect on the interactions between immobilized integrin and biotinylated soluble ligands (vitronectin or fibrinogen). The integrin preparations differ somewhat over time, thus the _v-selective cyclo(-Arg-Gly-Asp-D-Phe-Val-) was used as internal standard to allow interassay comparability.

Tumor Models.
Biodistribution of [¹⁸F]Galacto-RGD was evaluated in mice using a murine osteosarcoma and two xenotransplanted human melanoma models (M21 and M21-L). The osteosarcoma and the M21 melanoma cell line both express the _vß₃ integrin (11 , 12) . The melanoma M21-L cell line, which was selected for weak expression of the _vß₃ integrin, served as a negative control (12) .

Murine osteosarcomas induced by injection of strontium-90 were serially transplanted into female BALB/c mice. Tumor pieces of approximately 1 mm³ were injected by a trocar close to the femur into the musculus quadriceps. Human M21 and M21-L melanoma cells were cultured in a humidified atmosphere with 5% CO₂. The cell culture medium was RPMI 1640 (Seromed Biochrom, Berlin, Germany) supplemented with 10% FCS and gentamicin. Tumor xenografts were obtained by s.c. injection of 5 x 10⁶ cells (M21) or 1.5 x 10⁷ cells (M21-L) into the left flank of female nude mice. Mice bearing tumors weighing between 300 and 500 mg were used for biodistribution studies.

Biodistribution Studies.
Nude mice bearing tumor xenografts of human melanoma M21 or M21-L and BALB/c mice bearing murine osteosarcomas were i.v. injected with approximately 370 kBq of [¹⁸F]Galacto-RGD. The animals were sacrificed and dissected 10, 60, and 120 min after injection of [¹⁸F]Galacto-RGD. Blood, plasma, liver, kidney, muscle, heart, brain, lung, spleen, colon, femur, and tumor were removed and weighed. The radioactivity in the tissue was measured using a gamma counter. Results are expressed as the %ID/g. Each value represents the mean and SD of three to four animals.

Competition Studies.
Blocking of the _vß₃ integrin was completed by injecting 6 mg/kg cyclo(-Arg-Gly-Asp-D-Phe-Val-) 10 min before the injection of 370 kBq of the radioactive compound in 100 µl of PBS (pH 7.4). Animals were sacrificed and dissected 60 min after injection of [¹⁸F]Galacto-RGD. Further processing was carried out as described above.

PET Studies with a Dedicated Small Animal Scanner.
PET imaging of tumor-bearing mice was performed using a prototype small animal positron tomograph, Munich Avalanche Photodiode PET (13) . The animal scanner consists of two sectors, comprising three detector modules each, which rotate around the animal for acquisition of complete projections in one transaxial slice (30 angular steps). Each module consists of eight small (3.7 x 3.7 x 12 mm³) lutetium-oxy-orthosilicate crystals read out by arrays of avalanche photodiodes. List mode data are reconstructed using statistical, iterative methods including the spatially dependent line spread function. Reconstructed image resolution is 2.5 mm (full width at half maximum) in a transaxial field of view of 7.5 cm, and the slice thickness is 2 mm. Ninety min after the injection of approximately 5.5 MBq of [¹⁸F]Galacto-RGD, animals were positioned prone inside the tomograph, and a transaxial slice through the tumor region was measured for 35 min.

One melanoma M21-bearing mouse was imaged three times: (a) without pretreatment; (b) with 6 mg/kg cyclo(-Arg-Gly-Asp-d-Phe-Val-); and (c) with 18 mg/kg cyclo(-Arg-Gly-Asp-d-Phe-Val-) injected 10 min before the tracer. For comparison, one mouse with negative control melanoma M21-L was imaged. Tumor volume was approximately 0.5 ml for both tumor models. To assess tumor uptake of [¹⁸F]Galacto-RGD, circular regions of interest with a diameter of 5 mm were placed at the location of the maximum tracer uptake in the tumor and in the contralateral thorax wall (reference region). Relative tracer uptake was expressed as the ratio between mean counts in the tumor and in the reference region (tumor:background ratio).

	Results

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Labeling of cyclo(-Arg-Gly-Asp-D-Phe-Lys(SAA)-) using 4-nitrophenyl 2-[¹⁸F]fluoropropionate as a prosthetic group resulted in [¹⁸F]Galacto-RGD (Fig. 1) of high radiochemical purity (>98%). The decay-corrected radiochemical yield for the acylation step after RP-HPLC was approximately 50% within a total preparation time of about 40 min.

View larger version (18K): [in this window] [in a new window] [Download PPT slide]   Fig. 1. Schematic structure of [18F]Galacto-RGD. The glycopeptide shows the characteristic ßII’-turn with D-Phe in the i+1 position and the RGD site in a "kinked" conformation responsible for the vß3 selectivity.

The biodistribution data of [¹⁸F]Galacto-RGD in the three tumor models are summarized in Table 1 . [¹⁸F]Galacto-RGD showed rapid and predominantly renal excretion, resulting in a low activity concentration in blood and muscle as early as 60 min p.i. The initial activity accumulation in the _vß₃-expressing osteosarcoma and melanoma M21 was between 3% and 4% ID/g 10 min p.i., decreasing to about 1.5% ID/g 60 min p.i. and remaining constant until the end of the observation period. Moreover, at 120 min p.i., most organs showed lower activity uptake like the tumor for both models. Only liver, colon, and kidneys revealed a similar activity concentration to the tumor. The low activity accumulation in the bone indicated that the tracer is stable toward defluorination in vivo. Altogether, this led to high tumor:background ratios [e.g., tumor:blood, 13.2 (osteosarcoma) and 27.5 (M21); tumor:muscle: 6.0 (osteosarcoma) and 10.2 (M21)]. In contrast, the negative control tumors showed an initial tracer uptake of approximately 2% ID/g, which decreased to about 0.4% ID/g after 60 min p.i. Thus, the tracer uptake in the negative control tumor is 3.8 times lower than that in the _vß₃-positive tumor between 60 and 120 min (Fig. 2) . Pretreatment of the melanoma M21-bearing mice with 6 mg/kg of the _v-selective peptide cyclo(-Arg-Gly-Asp-D-Phe-Val-) reduced the tumor:blood ratio at 60 min p.i. from 8.7 to 1.5 and the tumor:muscle ratio from 7.4 to 4.2.

View larger version (21K): [in this window] [in a new window] [Download PPT slide]   Fig. 2. Comparison of the biodistribution data of [18F]Galacto-RGD in melanoma M21 ()- and M21-L ()-bearing nude mice. Error bars, 1 SD. For some data points, error bars are not visible because the SD is smaller than the size of the symbol.

View larger version (39K): [in this window] [in a new window] [Download PPT slide]   Fig. 3. Transaxial small animal PET images of nude mice bearing human melanoma xenografts. Images were acquired 90 min after injection of approximately 5.5 MBq of [18F]Galacto-RGD. The top left image shows selective accumulation of the tracer in the vß3-positve (M21) tumor on the left flank. In contrast, no focal tracer accumulation is visible in the vß3-negative (M21-L) control tumor (bottom left image). The three images on the right were obtained from serial [18F]Galacto-RGD PET studies in one mouse. These illustrate the dose-dependent blockade of tracer uptake by the v-selective cyclic pentapeptide cyclo(-Arg-Gly-Asp-D-Phe-Val-).

	Discussion

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Previously, we introduced radioiodinated cyclic RGD peptides for the imaging of _vß₃ integrin status (11) . These first-generation tracers showed receptor-specific accumulation in different tumor mouse models. However, these tracers also revealed high activity retention in liver and intestine, which limits the application for tumor imaging. For the present study, we improved the pharmacokinetics by introducing a SAA, which increased the hydrophilicity and markedly reduced the tracer uptake by the liver. Moreover, introduction of the SAA allows ¹⁸F-labeling of the amino methyl function of the glycopeptide using radiolabeled acylation reagents. The design of [¹⁸F]Galacto-RGD was based on our data from comprehensive structure activity investigations (3, 4, 5 , 14) . These studies demonstrated that the specific binding of the cyclic pentapeptides is determined by a "kinked" conformation of the RGD site (see Fig. 1 ). Introduction of a lysine and subsequent conjugation of the SAA are not expected to change the spatial structure of the peptide. Thus, these modifications are unlikely to influence the _vß₃ affinity of the compound. This was confirmed by the in vitro binding studies, which revealed a high _vß₃ affinity and selectivity for [¹⁸F]Galacto-RGD.

Moreover, [¹⁸F]Galacto-RGD showed rapid and predominantly renal excretion, resulting in a low tracer concentration in most of the organs (especially blood and muscle) and stable accumulation in the _vß₃-expressing tumor during the observation period (up to 120 min p.i.). These features permit high signal:noise ratios for in vivo imaging soon after injection (2 h), making this tracer suitable for PET studies using short-lived isotopes.

Recently, different nonpeptidic antagonists with high affinity and selectivity have been reported (6 , 7) . These low molecular mass compounds are optimized in size to fit the binding pocket of the receptor. Thus, introduction of labeling groups is likely to result in a loss of affinity. Sivolapenko et al. (15) described a ^99mTc-labeled linear decapeptide containing two RGD sites that had been used for imaging in one patient study. However, neither in vitro nor in vivo studies were carried out to demonstrate _vß₃ affinity and specificity of the peptide. Furthermore, the linear peptide showed high persistent background activity in the lung and abdomen. Most recently, preliminary data have been presented on a ¹¹¹In-labeled diethylenetriaminepenta-acetic acid-RGD analogue (16) , a dimeric, 12-amino acid _vß₃ antagonist labeled with ^99mTc or ¹¹¹In (17) , and ^99mTc-, ¹⁸⁶Re-, and ⁹⁰Y-labeled peptides based on cyclo(-Arg-Gly-Asp-D-Phe-Lys-) (18) . These compounds showed tumor-specific binding in vitro and in vivo.

However, the use of a PET tracer is preferable for imaging receptor expression because of the superior sensitivity and spatial resolution of PET and the ability to quantify regional tracer concentrations. As demonstrated by our study, these principal physical advantages of PET permit imaging of _vß₃ expression in living mice. Furthermore, we were able to demonstrate the feasibility of serial PET studies to determine the specific blockade of _vß₃ after injection of increasing amounts of cyclo(-Arg-Gly-Asp-D-Phe-Val-), a potent _v antagonist. This indicates that [¹⁸F]Galacto-RGD may also be used for monitoring anticancer therapy directed at the functional inhibition of _vß₃.

Although these data are very encouraging, the following limitations should also be noted. In this initial evaluation of [¹⁸F]Galacto-RGD, _vß₃ receptor density was not quantitatively determined for the tumor models. Furthermore, PET studies were analyzed by simple tumor:background ratios. Quantitative analysis of _vß₃ receptor density by PET imaging will require tracer kinetic analysis and correlation with the expression of the _vß₃ integrin using immunohistochemistry and Western blots. Nevertheless, the uptake of [¹⁸F]Galacto-RGD in _vß₃-positive tumors was four times higher than that in negative controls, and a specific antagonist was able to block up to 65% of [¹⁸F]Galacto-RGD uptake in receptor-positive tumors. Moreover, as reported previously (11) , the nonspecific radiolabeled cyclic pentapeptide 3-[¹²⁵I]iodo-Tyr⁴-cyclo(-Arg-D-Ala-Asp-Tyr-Val-) clearly showed lower tumor uptake for both tumor models (osteosarcoma, 0.48 ± 0.39% ID/g at 120 min p.i.; melanoma M21, 0.12 ± 0.04% ID/g at 120 min p.i.). Thus, our findings qualitatively demonstrate receptor specificity of [¹⁸F]Galacto-RGD in vivo. In addition, the good correlation between tumor:background ratios determined by small animal PET and invasive biodistribution studies clearly indicate the feasibility of quantitative evaluation of _vß₃ expression by PET imaging.

The use of n.c.a. [¹⁸F]Galacto-RGD in humans is not expected to lead to toxicity because plasma concentrations will be in the low nanomolar range. Furthermore, the short physical half-life of ¹⁸F (t_1/2 = 109.7 min) and rapid renal elimination of unbound tracer result in a low radiation dose. Thus, PET studies using [¹⁸F]Galacto-RGD may easily be translated from experimental settings to clinical studies.

Initial clinical trials evaluating the use of _vß₃ antagonists as antiangiogenic therapy in patients with various malignant tumors have been initiated (19) . In clinical studies, radiolabeled RGD peptides may be used to document _vß₃ expression of the tumors before the administration of _vß₃ antagonists, thus allowing appropriate selection of patients entering clinical trials. Furthermore, as demonstrated, [¹⁸F]Galacto-RGD may be used to assess the inhibition of the _vß₃ integrin by antagonists, a process by which optimization of the dose of _vß₃ antagonists may be achieved. Finally, _vß₃ expression has been reported to be an important factor in determining the invasiveness and metastatic potential of malignant tumors in experimental tumor models as well as in patient studies (20 , 21) . Therefore, noninvasive imaging of _vß₃ expression using [¹⁸F]Galacto-RGD and PET may provide a unique means of characterizing the biological aggressiveness of a malignant tumor in an individual patient.

In conclusion, our study demonstrates that [¹⁸F]Galacto-RGD is suitable for imaging of _vß₃ expression using PET. Moreover, we have shown that this tracer, in combination with a small animal PET scanner, may be used to monitor the blockade of _vß₃ by specific antagonists in living mice. We anticipate that noninvasive serial studies of _vß₃ expression and functional activity using PET will become an important tool to evaluate the role of _vß₃ during tumor progression and angiogenesis in basic research as well as in clinical studies.

	ACKNOWLEDGMENTS

 
The RDS-cyclotron team, particularly M. Herz, is acknowledged for routine radionuclide production. We thank W. Linke, S. Daum, F. Rau, and K. Fischer for excellent technical assistance and B. J. Pichler, G. Boening, and M. Rafecas for their contribution in preparing the PET images. We thank Dr. D. A. Cheresh for supplying us with M21 and M21-L melanoma cells.

	FOOTNOTES

 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by Grant 96.017.2 from the Sander-Foundation and in part by the German Reseach Foundation.

² To whom requests for reprints should be addressed, at Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, D-81675 München, Germany. Phone: 49-89-41404554; Fax: 49-89-41404841; E-mail: R.Haubner{at}lrz.tum.de

³ The abbreviations used are: PET, positron emission tomography; RP-HPLC, reversed-phase high performance liquid chromatography; SAA, sugar amino acid; Fprop, 2-fluoropropionyl; [¹⁸F]Galacto-RGD, cyclo(-Arg-Gly-Asp-D-Phe-Lys(([¹⁸F]Fprop)SAA)-); p.i., postinjection; %ID/g, percentage of the injected dose per gram of tissue; n.c.a., non-carrier added.

⁴ R. Haubner, H. J. Wester, C. Mang, S. L. Goodman, H. Kessler, and M. Schwaiger. Synthesis and in vitro evaluation of a RGD-containing glycopeptide for the noninvasive determination of the _vß₃ expression using PET, manuscript in preparation.

Received 8/ 7/00. Accepted 1/12/01.

	REFERENCES

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 

1. Clezardin P. Recent insights into the role of integrins in cancer metastasis. Cell. Mol. Life Sci., 54: 541-548, 1998.[Medline]
2. Stromblad S., Cheresh D. A. Integrins, angiogenesis and vascular cell survival. Chem. Biol., 3: 881-885, 1996.[Medline]
3. Gurrath M., Müller G., Kessler H., Aumailley M., Timpl R. Conformation/activity studies of rationally designed potent anti-adhesive RGD peptides. Eur. J. Biochem., 210: 911-921, 1992.[Medline]
4. Haubner R., Finsinger D., Kessler H. Stereoisomeric peptide libraries and peptidomimetics for designing selective inhibitors of the _vß₃ integrin for a new cancer therapy. Angew. Chem. Int. Ed. Engl., 36: 1374-1389, 1997.
5. Aumailley M., Gurrath M., Müller G., Calvete J., Timpl R., Kessler H. Arg-Gly-Asp constrained within cyclic pentapeptides. Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1. FEBS Lett., 291: 50-54, 1991.[Medline]
6. Carron C. P., Meyer D. M., Pegg J. A., Engleman V. W., Nickols M. A., Settle S. L., Westlin W. F., Ruminski P. G., Nickols G. A. A peptidomimetic antagonist of the integrin _vß₃ inhibits Leydig cell tumor growth and the development of hypercalcemia of malignancy. Cancer Res., 58: 1930-1935, 1998.[Abstract/Free Full Text]
7. Kerr J. S., Wexler R. S., Mousa S. A., Robinson C. S., Wexler E. J., Mohamed S., Voss M. E., Devenny J. J., Czerniak P. M., Gudzelak A., Jr., Slee A. M. Novel small molecule _v integrin antagonists: comparative anti-cancer efficacy with known angiogenesis inhibitors. Anticancer Res., 19: 959-968, 1999.[Medline]
8. Lode H. N., Moehler T., Xiang R., Jonczyk A., Gillies S. D., Cheresh D. A., Reisfeld R. A. Synergy between an antiangiogenic integrin _v antagonist and an antibody-cytokine fusion protein eradicates spontaneous tumor metastases. Proc. Natl. Acad. Sci. USA, 96: 1591-1596, 1999.[Abstract/Free Full Text]
9. Sipkins D. A., Cheresh D. A., Kazemi M. R., Nevin L. M., Bednarski M. D., Li K. C. P. Detection of tumor angiogenesis in vivo by _vß₃-targeted magnetic resonance imaging. Nat. Med., 5: 623-626, 1998.
10. Wester H. J., Hamacher K., Stöcklin G. A comparative study of n.c.a. fluorine-18 labeling of proteins via acylation and photochemical conjugation. Nucl. Med. Biol., 23: 365-372, 1996.[Medline]
11. Haubner R., Wester H. J., Reuning U., Senekowitsch-Schmidtke R., Diefenbach B., Kessler H., Stöcklin G., Schwaiger M. Radiolabeled _vß₃ integrin antagonists: a new class of tracers for tumor targeting. J. Nucl. Med., 40: 1061-1071, 1999.[Abstract/Free Full Text]
12. Cheresh D. A., Spiro R. C. Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. J. Biol. Chem., 262: 17703-17711, 1987.[Abstract/Free Full Text]
13. Ziegler S. I., Pichler B. J., Boening G., Rafecas M., Pimpl W., Lorenz E., Schmitz N., Schwaiger M. A prototype high resolution animal positron tomograph with avalanche photodiode arrays and LSO crystals. Eur. J. Nucl. Med., 28: 136-143, 2001.[Medline]
14. Haubner R., Gratias R., Diefenbach B., Goodman S. L., Jonczyk A., Kessler H. Structural and functional aspects of RGD-containing cyclic pentapeptides as highly potent and selective integrin _vß₃ antagonists. J. Am. Chem. Soc., 118: 7461-7472, 1996.
15. Sivolapenko G. B., Skarlos D., Pectasides D., Stathopoulou E., Milonakis A., Sirmalis G., Stuttle A., Courtenay-Luck N. S., Konstantinides K., Epenetos A. A. Imaging of metastatic melanoma utilising a technetium-99m-labelled RGD-containing synthetic peptide. Eur. J. Nucl. Med., 25: 1383-1389, 1998.[Medline]
16. De Jong M., Van Hagen P. M., Breeman W. A., Bernard H. F., Schaar M., Van Gameren A., Srinivasan A., Schmidt M., Bugaj J. E., Krenning E. P. Evaluation of a radiolabeled cyclic DTPA-RGD analog for tumor imaging and radionuclide therapy. J. Nucl. Med., 41: 232P 2000.
17. Janssen M. L. H., Boerman O. C., Edwards D. S., Barnett J. A., Rajopadhye W. J., Oyen G., Corstens F. H. M. ¹¹¹In- and ^99mTc-labeled peptides against the _vß₃ integrin: a new target for radionuclide peptide targeting of tumors. J. Nucl. Med., 41: 33P 2000.
18. Bock M., Bruchertseifer F., Haubner R., Senekowitsch-Schmidtke R., Kessler H., Schwaiger M., Wester H. J. Tc-99m-, Re-188- and Y-90-labeled _vß₃ antagonists: promising tracer for tumor-induced angiogenesis. J. Nucl. Med., 41: 41P 2000.
19. Brower V. Tumor angiogenesis-new drugs on the block. Nat. Biotechnol., 17: 963-968, 1999.[Medline]
20. Felding-Habermann B., Mueller B. M., Romerdahl C. A., Cheresh D. A. Involvement of integrin _v gene expression in human melanoma tumorigenicity. J. Clin. Investig., 89: 2018-2022, 1992.
21. Gasparini G., Brooks P. C., Biganzoli E., Vermeulen P. B., Bonoldi E., Dirix L. Y., Ranieri G., Miceli R., Cheresh D. A. Vascular integrin _vß₃: a new prognostic indicator in breast cancer. Clin. Cancer Res., 4: 2625-2634, 1998.[Abstract]

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				G. Z. Ferl, R. A. Dumont, I. J. Hildebrandt, A. Armijo, R. Haubner, G. Reischl, H. Su, W. A. Weber, and S.-C. Huang Derivation of a Compartmental Model for Quantifying 64Cu-DOTA-RGD Kinetics in Tumor-Bearing Mice J. Nucl. Med., February 1, 2009; 50(2): 250 - 258. [Abstract] [Full Text] [PDF]

				M. S. Morrison, S.-A. Ricketts, J. Barnett, A. Cuthbertson, J. Tessier, and S. R. Wedge Use of a Novel Arg-Gly-Asp Radioligand, 18F-AH111585, to Determine Changes in Tumor Vascularity After Antitumor Therapy J. Nucl. Med., January 1, 2009; 50(1): 116 - 122. [Abstract] [Full Text] [PDF]

				H. F. Langer, R. Haubner, B. J. Pichler, and M. Gawaz Radionuclide imaging a molecular key to the atherosclerotic plaque. J. Am. Coll. Cardiol., July 1, 2008; 52(1): 1 - 12. [Abstract] [Full Text] [PDF]

				W. Cai and X. Chen Multimodality Molecular Imaging of Tumor Angiogenesis J. Nucl. Med., June 1, 2008; 49(Suppl_2): 113S - 128S. [Abstract] [Full Text] [PDF]

				D. A. Mankoff, J. M. Link, H. M. Linden, L. Sundararajan, and K. A. Krohn Tumor Receptor Imaging J. Nucl. Med., June 1, 2008; 49(Suppl_2): 149S - 163S. [Abstract] [Full Text] [PDF]

				T. Higuchi, F. M. Bengel, S. Seidl, P. Watzlowik, H. Kessler, R. Hegenloh, S. Reder, S. G. Nekolla, H. J. Wester, and M. Schwaiger Assessment of {alpha}v{beta}3 integrin expression after myocardial infarction by positron emission tomography Cardiovasc Res, May 1, 2008; 78(2): 395 - 403. [Abstract] [Full Text] [PDF]

				M. Picchio, R. Beck, R. Haubner, S. Seidl, H.-J. Machulla, T. D. Johnson, H.-J. Wester, G. Reischl, M. Schwaiger, and M. Piert Intratumoral Spatial Distribution of Hypoxia and Angiogenesis Assessed by 18F-FAZA and 125I-Gluco-RGD Autoradiography J. Nucl. Med., April 1, 2008; 49(4): 597 - 605. [Abstract] [Full Text] [PDF]

				Z.-B. Li, Z. Wu, K. Chen, E. K. Ryu, and X. Chen 18F-Labeled BBN-RGD Heterodimer for Prostate Cancer Imaging J. Nucl. Med., March 1, 2008; 49(3): 453 - 461. [Abstract] [Full Text] [PDF]

				A. J. Beer, M. Niemeyer, J. Carlsen, M. Sarbia, J. Nahrig, P. Watzlowik, H.-J. Wester, N. Harbeck, and M. Schwaiger Patterns of {alpha}v{beta}3 Expression in Primary and Metastatic Human Breast Cancer as Shown by 18F-Galacto-RGD PET J. Nucl. Med., February 1, 2008; 49(2): 255 - 259. [Abstract] [Full Text] [PDF]

				L. Peng, R. Liu, M. Andrei, W. Xiao, and K. S. Lam In vivo optical imaging of human lymphoma xenograft using a library-derived peptidomimetic against {alpha}4{beta}1 integrin Mol. Cancer Ther., February 1, 2008; 7(2): 432 - 437. [Abstract] [Full Text] [PDF]

				L. L. Johnson, L. Schofield, T. Donahay, M. Bouchard, A. Poppas, and R. Haubner Radiolabeled RGD Peptides to Image Angiogenesis in Swine Model of Hibernating Myocardium. J. Am. Coll. Cardiol. Img., January 1, 2008; 1: 500 - 510. [Abstract] [Full Text] [PDF]

				A. J. Beer, S. Lorenzen, S. Metz, K. Herrmann, P. Watzlowik, H.-J. Wester, C. Peschel, F. Lordick, and M. Schwaiger Comparison of Integrin {alpha}v 3 Expression and Glucose Metabolism in Primary and Metastatic Lesions in Cancer Patients: A PET Study Using 18F-Galacto-RGD and 18F-FDG J. Nucl. Med., January 1, 2008; 49(1): 22 - 29. [Abstract] [Full Text] [PDF]

				A. J. Beer, A.-L. Grosu, J. Carlsen, A. Kolk, M. Sarbia, I. Stangier, P. Watzlowik, H.-J. Wester, R. Haubner, and M. Schwaiger [18F]Galacto-RGD Positron Emission Tomography for Imaging of {alpha}v{beta}3 Expression on the Neovasculature in Patients with Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., November 15, 2007; 13(22): 6610 - 6616. [Abstract] [Full Text] [PDF]

				Z. Wu, Z.-B. Li, K. Chen, W. Cai, L. He, F. T. Chin, F. Li, and X. Chen microPET of Tumor Integrin {alpha}v{beta}3 Expression Using 18F-Labeled PEGylated Tetrameric RGD Peptide (18F-FPRGD4) J. Nucl. Med., September 1, 2007; 48(9): 1536 - 1544. [Abstract] [Full Text] [PDF]

				S. H. Hausner, D. DiCara, J. Marik, J. F. Marshall, and J. L. Sutcliffe Use of a Peptide Derived from Foot-and-Mouth Disease Virus for the Noninvasive Imaging of Human Cancer: Generation and Evaluation of 4-[18F]Fluorobenzoyl A20FMDV2 for In vivo Imaging of Integrin {alpha}v{beta}6 Expression with Positron Emission Tomography Cancer Res., August 15, 2007; 67(16): 7833 - 7840. [Abstract] [Full Text] [PDF]

				R. Rossin, D. Berndorff, M. Friebe, L. M. Dinkelborg, and M. J. Welch Small-Animal PET of Tumor Angiogenesis Using a 76Br-Labeled Human Recombinant Antibody Fragment to the ED-B Domain of Fibronectin J. Nucl. Med., July 1, 2007; 48(7): 1172 - 1179. [Abstract] [Full Text] [PDF]

				H.-J. Wester Nuclear Imaging Probes: from Bench to Bedside Clin. Cancer Res., June 15, 2007; 13(12): 3470 - 3481. [Abstract] [Full Text] [PDF]

				J. E. Sprague, H. Kitaura, W. Zou, Y. Ye, S. Achilefu, K. N. Weilbaecher, S. L. Teitelbaum, and C. J. Anderson Noninvasive Imaging of Osteoclasts in Parathyroid Hormone-Induced Osteolysis Using a 64Cu-Labeled RGD Peptide J. Nucl. Med., February 1, 2007; 48(2): 311 - 318. [Abstract] [Full Text] [PDF]

				G. Mariani, P. A. Erba, and A. Signore Receptor-Mediated Tumor Targeting with Radiolabeled Peptides: There Is More to It than Somatostatin Analogs J. Nucl. Med., December 1, 2006; 47(12): 1904 - 1907. [Full Text] [PDF]

				K.-H. Jung, K.-H. Lee, J.-Y. Paik, B.-H. Ko, J.-S. Bae, B. C. Lee, H. J. Sung, D. H. Kim, Y. S. Choe, and D. Y. Chi Favorable Biokinetic and Tumor-Targeting Properties of 99mTc-Labeled Glucosamino RGD and Effect of Paclitaxel Therapy J. Nucl. Med., December 1, 2006; 47(12): 2000 - 2007. [Abstract] [Full Text] [PDF]

				W. Cai, J. Rao, S. S. Gambhir, and X. Chen How molecular imaging is speeding up antiangiogenic drug development. Mol. Cancer Ther., November 1, 2006; 5(11): 2624 - 2633. [Abstract] [Full Text] [PDF]

				W. Cai, Y. Wu, K. Chen, Q. Cao, D. A. Tice, and X. Chen In vitro and In vivo Characterization of 64Cu-Labeled AbegrinTM, a Humanized Monoclonal Antibody against Integrin {alpha}v{beta}3 Cancer Res., October 1, 2006; 66(19): 9673 - 9681. [Abstract] [Full Text] [PDF]

				W. A. Weber Positron Emission Tomography As an Imaging Biomarker J. Clin. Oncol., July 10, 2006; 24(20): 3282 - 3292. [Abstract] [Full Text] [PDF]

				W. Cai, X. Zhang, Y. Wu, and X. Chen A Thiol-Reactive 18F-Labeling Agent, N-[2-(4-18F-Fluorobenzamido)Ethyl]Maleimide, and Synthesis of RGD Peptide-Based Tracer for PET Imaging of {alpha}v{beta}3 Integrin Expression J. Nucl. Med., July 1, 2006; 47(7): 1172 - 1180. [Abstract] [Full Text] [PDF]

				A. J. Beer, R. Haubner, M. Sarbia, M. Goebel, S. Luderschmidt, A. L. Grosu, O. Schnell, M. Niemeyer, H. Kessler, H.-J. Wester, et al. Positron Emission Tomography Using [18F]Galacto-RGD Identifies the Level of Integrin {alpha}v{beta}3 Expression in Man. Clin. Cancer Res., July 1, 2006; 12(13): 3942 - 3949. [Abstract] [Full Text] [PDF]

				V. Askoxylakis, W. Mier, S. Zitzmann, V. Ehemann, J. Zhang, S. Kramer, C. Beck, M. Schwab, M. Eisenhut, and U. Haberkorn Characterization and Development of a Peptide (p160) with Affinity for Neuroblastoma Cells J. Nucl. Med., June 1, 2006; 47(6): 981 - 988. [Abstract] [Full Text] [PDF]

				A. J. Beer, R. Haubner, I. Wolf, M. Goebel, S. Luderschmidt, M. Niemeyer, A.-L. Grosu, M.-J. Martinez, H. J. Wester, W. A. Weber, et al. PET-Based Human Dosimetry of 18F-Galacto-RGD, a New Radiotracer for Imaging {alpha}v{beta}3 Expression J. Nucl. Med., May 1, 2006; 47(5): 763 - 769. [Abstract] [Full Text] [PDF]

				X. Zhang, Z. Xiong, Y. Wu, W. Cai, J. R. Tseng, S. S. Gambhir, and X. Chen Quantitative PET Imaging of Tumor Integrin {alpha}v{beta}3 Expression with 18F-FRGD2 J. Nucl. Med., January 1, 2006; 47(1): 113 - 121. [Abstract] [Full Text] [PDF]

				H.-J. Wester and H. Kessler Molecular Targeting with Peptides or Peptide-Polymer Conjugates: Just a Question of Size? J. Nucl. Med., December 1, 2005; 46(12): 1940 - 1945. [Full Text] [PDF]

				G. J. Kelloff, K. A. Krohn, S. M. Larson, R. Weissleder, D. A. Mankoff, J. M. Hoffman, J. M. Link, K. Z. Guyton, W. C. Eckelman, H. I. Scher, et al. The Progress and Promise of Molecular Imaging Probes in Oncologic Drug Development Clin. Cancer Res., November 15, 2005; 11(22): 7967 - 7985. [Abstract] [Full Text] [PDF]

				A-L Grosu, M Piert, and M Molls Experience of PET for target localisation in radiation oncology Br. J. Radiol., November 1, 2005; Supplement_28(1): 18 - 32. [Full Text] [PDF]

				Y. Wu, X. Zhang, Z. Xiong, Z. Cheng, D. R. Fisher, S. Liu, S. S. Gambhir, and X. Chen microPET Imaging of Glioma Integrin {alpha}v{beta}3 Expression Using 64Cu-Labeled Tetrameric RGD Peptide J. Nucl. Med., October 1, 2005; 46(10): 1707 - 1718. [Abstract] [Full Text] [PDF]

				V. Askoxylakis, S. Zitzmann, W. Mier, K. Graham, S. Kramer, F. von Wegner, R. H.A. Fink, M. Schwab, M. Eisenhut, and U. Haberkorn Preclinical Evaluation of the Breast Cancer Cell-Binding Peptide, p160 Clin. Cancer Res., September 15, 2005; 11(18): 6705 - 6712. [Abstract] [Full Text] [PDF]

				B. R. Line, A. Mitra, A. Nan, and H. Ghandehari Targeting Tumor Angiogenesis: Comparison of Peptide and Polymer-Peptide Conjugates J. Nucl. Med., September 1, 2005; 46(9): 1552 - 1560. [Abstract] [Full Text] [PDF]

				S. Achilefu, S. Bloch, M. A. Markiewicz, T. Zhong, Y. Ye, R. B. Dorshow, B. Chance, and K. Liang Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression PNAS, May 31, 2005; 102(22): 7976 - 7981. [Abstract] [Full Text] [PDF]

				K.-H. Lee, K.-H. Jung, S.-H. Song, D. H. Kim, B. C. Lee, H. J. Sung, Y.-M. Han, Y. S. Choe, D. Y. Chi, and B.-T. Kim Radiolabeled RGD Uptake and {alpha}v Integrin Expression Is Enhanced in Ischemic Murine Hindlimbs J. Nucl. Med., March 1, 2005; 46(3): 472 - 478. [Abstract] [Full Text] [PDF]

				G. Gasparini, R. Longo, M. Fanelli, and B. A. Teicher Combination of Antiangiogenic Therapy With Other Anticancer Therapies: Results, Challenges, and Open Questions J. Clin. Oncol., February 20, 2005; 23(6): 1295 - 1311. [Abstract] [Full Text] [PDF]

				J. C. Miller, H. H. Pien, D. Sahani, A. G. Sorensen, and J. H. Thrall Imaging Angiogenesis: Applications and Potential for Drug Development J Natl Cancer Inst, February 2, 2005; 97(3): 172 - 187. [Abstract] [Full Text] [PDF]

				G. E.R. Weller, M. K.K. Wong, R. A. Modzelewski, E. Lu, A. L. Klibanov, W. R. Wagner, and F. S. Villanueva Ultrasonic Imaging of Tumor Angiogenesis Using Contrast Microbubbles Targeted via the Tumor-Binding Peptide Arginine-Arginine-Leucine Cancer Res., January 15, 2005; 65(2): 533 - 539. [Abstract] [Full Text] [PDF]

				M. R. Lewis Radiolabeled RGD Peptides Move Beyond Cancer: PET Imaging of Delayed-Type Hypersensitivity Reaction J. Nucl. Med., January 1, 2005; 46(1): 2 - 4. [Full Text] [PDF]

				B. J. Pichler, M. Kneilling, R. Haubner, H. Braumuller, M. Schwaiger, M. Rocken, and W. A. Weber Imaging of Delayed-Type Hypersensitivity Reaction by PET and 18F-Galacto-RGD J. Nucl. Med., January 1, 2005; 46(1): 184 - 189. [Abstract] [Full Text] [PDF]

				X. Chen, P. S. Conti, and R. A. Moats In vivo Near-Infrared Fluorescence Imaging of Integrin {alpha}v{beta}3 in Brain Tumor Xenografts Cancer Res., November 1, 2004; 64(21): 8009 - 8014. [Abstract] [Full Text] [PDF]

				X. Chen, Y. Hou, M. Tohme, R. Park, V. Khankaldyyan, I. Gonzales-Gomez, J. R. Bading, W. E. Laug, and P. S. Conti Pegylated Arg-Gly-Asp Peptide: 64Cu Labeling and PET Imaging of Brain Tumor {alpha}v{beta}3-Integrin Expression J. Nucl. Med., October 1, 2004; 45(10): 1776 - 1783. [Abstract] [Full Text] [PDF]

				K. Pacak, G. Eisenhofer, and D. S. Goldstein Functional Imaging of Endocrine Tumors: Role of Positron Emission Tomography Endocr. Rev., August 1, 2004; 25(4): 568 - 580. [Abstract] [Full Text] [PDF]

				X. Chen, R. Park, Y. Hou, M. Tohme, A. H. Shahinian, J. R. Bading, and P. S. Conti microPET and Autoradiographic Imaging of GRP Receptor Expression with 64Cu-DOTA-[Lys3]Bombesin in Human Prostate Adenocarcinoma Xenografts J. Nucl. Med., August 1, 2004; 45(8): 1390 - 1397. [Abstract] [Full Text] [PDF]

				R. E. Reiman, W. Brenner, J. F. Eary, and K. H. Bohuslavizki PET Tracers for Osteosarcoma J. Nucl. Med., August 1, 2004; 45(8): 1424 - 1425. [Full Text] [PDF]

				M. Schottelius, T. Poethko, M. Herz, J.-C. Reubi, H. Kessler, M. Schwaiger, and H.-J. Wester First 18F-Labeled Tracer Suitable for Routine Clinical Imaging of sst Receptor-Expressing Tumors Using Positron Emission Tomography Clin. Cancer Res., June 1, 2004; 10(11): 3593 - 3606. [Abstract] [Full Text] [PDF]

				T. Poethko, M. Schottelius, G. Thumshirn, U. Hersel, M. Herz, G. Henriksen, H. Kessler, M. Schwaiger, and H.-J. Wester Two-Step Methodology for High-Yield Routine Radiohalogenation of Peptides: 18F-Labeled RGD and Octreotide Analogs J. Nucl. Med., May 1, 2004; 45(5): 892 - 902. [Abstract] [Full Text] [PDF]

				S. H. Britz-Cunningham and S. J. Adelstein Molecular Targeting with Radionuclides: State of the Science J. Nucl. Med., December 1, 2003; 44(12): 1945 - 1961. [Abstract] [Full Text] [PDF]

				G J R Cook Oncological molecular imaging: nuclear medicine techniques Br. J. Radiol., December 1, 2003; 76(suppl_2): S152 - S158. [Full Text] [PDF]

				D. B. Ellegala, H. Leong-Poi, J. E. Carpenter, A. L. Klibanov, S. Kaul, M. E. Shaffrey, J. Sklenar, and J. R. Lindner Imaging Tumor Angiogenesis With Contrast Ultrasound and Microbubbles Targeted to {alpha}v{beta}3 Circulation, July 22, 2003; 108(3): 336 - 341. [Abstract] [Full Text] [PDF]

				W. Brenner, K. H. Bohuslavizki, and J. F. Eary PET Imaging of Osteosarcoma J. Nucl. Med., June 1, 2003; 44(6): 930 - 942. [Abstract] [Full Text] [PDF]

				M. Santimaria, G. Moscatelli, G. L. Viale, L. Giovannoni, G. Neri, F. Viti, A. Leprini, L. Borsi, P. Castellani, L. Zardi, et al. Immunoscintigraphic Detection of the ED-B Domain of Fibronectin, a Marker of Angiogenesis, in Patients with Cancer Clin. Cancer Res., February 1, 2003; 9(2): 571 - 579. [Abstract] [Full Text] [PDF]

				H. Leong-Poi, J. Christiansen, A. L. Klibanov, S. Kaul, and J. R. Lindner Noninvasive Assessment of Angiogenesis by Ultrasound and Microbubbles Targeted to {alpha}v-Integrins Circulation, January 28, 2003; 107(3): 455 - 460. [Abstract] [Full Text] [PDF]

				M. L. Janssen, W. J. Oyen, I. Dijkgraaf, L. F. Massuger, C. Frielink, D. S. Edwards, M. Rajopadhye, H. Boonstra, F. H. Corstens, and O. C. Boerman Tumor Targeting with Radiolabeled {alpha}v{beta}3 Integrin Binding Peptides in a Nude Mouse Model Cancer Res., November 1, 2002; 62(21): 6146 - 6151. [Abstract] [Full Text] [PDF]

				M Schwaiger Functional imaging for assessment of therapy Br. J. Radiol., November 1, 2002; 75(90009): S67 - 73. [Full Text] [PDF]

				D. R. Collingridge, V. A. Carroll, M. Glaser, E. O. Aboagye, S. Osman, O. C. Hutchinson, H. Barthel, S. K. Luthra, F. Brady, R. Bicknell, et al. The Development of [124I]Iodinated-VG76e: A Novel Tracer for Imaging Vascular Endothelial Growth Factor in Vivo Using Positron Emission Tomography Cancer Res., October 15, 2002; 62(20): 5912 - 5919. [Abstract] [Full Text] [PDF]

				S. Zitzmann, V. Ehemann, and M. Schwab Arginine-Glycine-Aspartic Acid (RGD)-Peptide Binds to Both Tumor and Tumor-Endothelial Cells in Vivo Cancer Res., September 15, 2002; 62(18): 5139 - 5143. [Abstract] [Full Text] [PDF]

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