Purpose: The study was undertaken to develop and evaluate the potential of an integrin a v b 6-binding peptide (a v b 6-BP) for noninvasive imaging of a diverse range of malignancies with PET. Experimental Design: The peptide a v b 6-BP was prepared on solid phase and radiolabeled with 4-[ 18 F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired a v b 6-expressing and a v b 6-null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired a v b 6-expressing and a v b 6-null cell xenografts. A first-inhuman PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer. Results: [ 18 F]a v b 6-BP displayed excellent affinity and selectivity for the integrin a v b 6 in vitro [IC 50 (a v b 6) ¼ 1.2 nmol/L vs IC 50 (a v b 3) >10 mmol/L] in addition to rapid target-specific cell binding and internalization (72.5% AE 0.9% binding and 52.5% AE 1.8%, respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [ 18 F]a v b 6-BP was rapid, primarily via the kidneys. In patients, [ 18 F]a v b 6-BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [ 18 F]a v b 6-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung. Conclusions: The clinical impact of [ 18 F]a v b 6-BP PET imaging demonstrated in this first-inhuman study is immediate for a broad spectrum of malignancies.

The purpose of this study is to examine the melanocortin-1 receptor (MC1R) targeting and specificity of 203 Pb-DOTA-GGNle-CycMSH hex in melanoma cells and tumors to facilitate its potential therapeutic application when labeled with 212 Pb. The melanocortin-1 receptor (MC1R)specific targeting and imaging properties of 203 Pb-DOTA-GGNle-CycMSH hex were determined on B16/F1 and B16/F10 murine melanoma cells, and in B16/F1 flank melanoma-, B16/F10 flank melanoma-and B16/F10 pulmonary metastatic melanoma-bearing C57 mice. 203 Pb-DOTA-GGNle-CycMSH hex displayed MC1R-specific binding on B16/F1 and B16/F10 melanoma cells and tumors. B16/F1 flank melanoma, B16/F10 flank melanoma and B16/F10 pulmonary metastatic melanoma lesions could be clearly imaged by single photon emission computed tomography (SPECT) using 203 Pb-DOTA-GGNle-CycMSH hex as an imaging probe. The favorable melanoma targeting and imaging properties highlighted the potential of 203 Pb-DOTA-GGNle-CycMSH hex as a MC1R-targeting melanoma imaging probe, and warranted the evaluation of 212 Pb-DOTA-GGNle-CycMSH hex for melanoma therapy in future studies.

<p>Describes additional methods</p>

<p>Shows the maximum standard uptake values (SUVmax) at the 1 and 3 hour time points for the five subjects, decay corrected to the time of injection.</p>

<p>Shows the biodistribution data for [18F]αvβ6-BP in mice bearing paired αvβ6-expressing DX3puroβ6 and non-αvβ6-expressing DX3puro xenograft tumors at 1, 2 and 4 h p.i. and at 1 h p.i. after pre-administration of blocking peptide. Tissue uptake is expressed as decay-corrected percent injected dose per gram of tissue (dc % ID/g)</p>