Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Impact of Tumor Burden on Normal Organ Uptake

Abstract Background Epidermal growth factor receptors (EGFR) are overexpressed on many head and neck squamous cell carcinoma (HNSCC). Radioimmunotherapy (RIT) with F(ab')2 of the anti-EGFR monoclonal antibody panitumumab labeled with the β-particle emitter, 177Lu may be a promising treatment for HNSCC. Our aim was to assess the feasibility of a theranostic strategy that combines positron emission tomography (PET) with [64Cu]Cu-DOTA-panitumumab F(ab')2 to image HNSCC and predict the radiation equivalent doses to the tumour and normal organs from RIT with [177Lu]Lu-DOTA-panitumumab F(ab')2. Results Panitumumab F(ab')2 were conjugated to DOTA and complexed to 64Cu or 177Lu in high radiochemical purity (95.6 ± 2.1% and 96.7 ± 3.5%, respectively) and exhibited high affinity EGFR binding (Kd = 2.9 ± 0.7 × 10− 9 mol/L). Biodistribution (BOD) studies at 6, 24 or 48 h post-injection (p.i.) of [64Cu]Cu-DOTA-panitumumab F(ab')2 (5.5–14.0 MBq; 50 μg) or [177Lu]Lu-DOTA-panitumumab F(ab')2 (6.5 MBq; 50 μg) in NRG mice with s.c. HNSCC patient-derived xenografts (PDX) overall showed no significant differences in tumour uptake but modest differences in normal organ uptake were noted at certain time points. Tumours were imaged by microPET/CT with [64Cu]Cu-DOTA-panitumumab F(ab')2 or microSPECT/CT with [177Lu]Lu-DOTA-panitumumab F(ab')2 but not with irrelevant [177Lu]Lu-DOTA-trastuzumab F(ab')2. Tumour uptake at 24 h p.i. of [64Cu]Cu-DOTA-panitumumab F(ab')2 [14.9 ± 1.1% injected dose/gram (%ID/g) and [177Lu]Lu-DOTA-panitumumab F(ab')2 (18.0 ± 0.4%ID/g) were significantly higher (P < 0.05) than [177Lu]Lu-DOTA-trastuzumab F(ab')2 (2.6 ± 0.5%ID/g), demonstrating EGFR-mediated tumour uptake. There were no significant differences in the radiation equivalent doses in the tumour and most normal organs estimated for [177Lu]Lu-DOTA-panitumumab F(ab')2 based on the BOD of [64Cu]Cu-DOTA-panitumumab F(ab')2 compared to those estimated directly from the BOD of [177Lu]Lu-DOTA-panitumumab F(ab')2 except for the liver and whole body which were modestly underestimated by [64Cu]Cu-DOTA-panitumumab F(ab')2. Region-of-interest (ROI) analysis of microPET/CT images provided dose estimates for the tumour and liver that were not significantly different for the two radioimmunoconjugates. Human doses from administration of [177Lu]Lu-DOTA-panitumumab F(ab')2 predicted that a 2 cm diameter HNSCC tumour in a patient would receive 1.1–1.5 mSv/MBq and the whole body dose would be 0.15–0.22 mSv/MBq. Conclusion A PET theranostic strategy combining [64Cu]Cu-DOTA-panitumumab F(ab')2 to image HNSCC tumours and predict the equivalent radiation doses in the tumour and normal organs from RIT with [177Lu]Lu-DOTA-panitumumab F(ab')2 is feasible. RIT with [177Lu]Lu-DOTA-panitumumab F(ab')2 may be a promising approach to treatment of HNSCC due to frequent overexpression of EGFR.

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Effect of IGF-1R inhibitor BMS-754807 on tumor glucose metabolism and proliferation in Sal-IGF xenografts by FDG and FLT- PET imaging

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e14501 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e14501-e14501

Author(s):

P. L. Chow ◽

C. P. Ho ◽

D. Kan ◽

R. M. Attar ◽

F. Graf Finckenstein ◽

...

Keyword(s):

Pet Imaging ◽

Fdg Pet ◽

Critical Role ◽

Salivary Gland Tumor ◽

Human Tumor ◽

Tumor Burden ◽

Imaging Biomarkers ◽

Flt Pet ◽

Concomitant Reduction ◽

Pet Scans

e14501 Background: The type 1 insulin-like growth factor receptor (IGF-1R) plays a critical role in mitogenesis and survival in a variety of human tumor cells. IGF-1R is also closely related to the insulin receptor (IR). It is becoming increasingly evident that stimulation of IR or IR/IGF-1R hybrid receptors by insulin or IGF-1/2 may contribute to cancer growth, suggesting that both IGF-1R and IR may be targets for cancer therapy. BMS-754807 (‘807) is an oral IGF-1R tyrosine kinase antagonist under development that also blocks IR activity. This study explores the feasibility of fluorodeoxyglucose (FDG) and fluorothymidine (FLT) positron emission tomography (PET) as pharmacodynamic imaging biomarkers in a xenograft model. Methods: Mice were implanted with fragments of Sal-IGF, a transgenic salivary gland tumor expressing constitutively active IGF-1R. Once tumors reached desired size, the mice were divided into 3 treatment groups (vehicle, 6.25 mg/kg ‘807, & 50 mg/kg ‘807 on days 1–4). FDG-PET scans were performed on day -2 (prior to treatment), days 1 & 2 (max/min concentrations post day 1 dose), and days 4 & 5 (max/min day 4 dose). FLT-PET scans were performed on days -2, 2 (min day 1 dose), & 5 (min day 4 dose). Results: With FDG-PET imaging, a 66% reduction (P<0.05, paired t-test) in tumor SUVmean was observed at the end of the 50 mg/kg therapy (day 4) and sustained for 24h (day 5) with a concomitant reduction of 37% in tumor burden by day 5 (P<0.05). FLT-PET studies demonstrated a 45% reduction (P<0.05) in tumor SUVmean observed 24h after the end of 50 mg/kg therapy (day 5) with a concomitant reduction of 50% in tumor burden (day 5, P<0.05). Conclusions: Correlation with tumor growth inhibition suggests feasibility of FDG- PET despite IR blockade. These results support the use of both FDG and FLT PET imaging in clinical trials with ‘807. [Table: see text]

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Normal organ standard uptake values in carbon-11 acetate PET imaging

Nuclear Medicine Communications ◽

10.1097/mnm.0b013e32832aa7ce ◽

2009 ◽

Vol 30 (6) ◽

pp. 462-465 ◽

Cited By ~ 12

Author(s):

Won S. Song ◽

Brett R. Nielson ◽

Kevin P. Banks ◽

Yong C. Bradley

Keyword(s):

Pet Imaging ◽

Normal Organ

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