, Volume 19, Issue 3, pp 145–163 | Cite as

Radiolabeled Peptides in Oncology

Role in Diagnosis and Treatment
Drug Development


There has been an exponential growth in the development of radiolabeled peptides for diagnostic and therapeutic applications in the last decade. The automated means of synthesizing these compounds in large quantities and the simplified methods of purifying, characterizing, and optimizing them have kindled attention to peptides as carrier molecules. These new techniques have accelerated the commercial development of radiolabelled peptides, which has provided additional radiopharmaceuticals for the nuclear medicine community.

Peptides have many key properties including fast clearance, rapid tissue penetration, and low antigenicity, and can be produced easily and inexpensively. However, there may be problems with in vivo catabolism, unwanted physiologic effects, and chelate attachment. Radiolabeled peptides have made their greatest impact in the management of relatively rare neuroendocrine malignancies. Indeed, Indium-111 (111In)-pentetreotide (111In-DTPA-octreotide, Octreoscan®), which binds to somatostatin receptors (SSTRs), has become the diagnostic ‘gold standard’ in these diseases. However, 111In-pentetreotide has been less successful in the diagnosis of other more prevalent diseases in which SSTRs are upregulated. Technetium-99m (99mTc)-depreotide (NeoTect™), a 99mTc-labeled SSTR-analog, could have wider impact since it has high sensitivity and specificity for lung cancer lesion detection. However, this impact may be minimized by the increased availability of positron emission tomography imaging with Fluorine-18 (18F)-flourodeoxyglucose, which has similar sensitivity and specificity for lesion identification in this disease, and is currently more widely used. The receptors for bombesin, α-melanocyte-stimulating hormone, neurotensin, and the integrin αvβ3, are under active investigation as targets for radiolabelled peptides, but are still in the pre-clinical stage. Compounds directed at the cholecystokinin-B/gastrin receptor have shown promising results in clinical trials in humans.

Radiolabelled peptide therapy is usually indicated for patients with widespread disease that is not amenable to focused radiation therapy or is refractory to chemotherapy. Phase I/II studies using various radiolabelled peptides (including 111In-pentetreotide, Yttrium-90 [90Y]-DOTA-Phe1-Tyr3-octreotide, 90Y-DOTA-lanreotide, and Lutetium-177 [177Lu]-DOTA-octreotate) for the treatment of patients with neuroendocrine malignancy are in progress. Over 400 patients have been treated, and the response rate has ranged from 60% to 75%, although few patients have had a complete response. Patients have been given individual doses ranging from 2 to 11 GBq with a slow infusion every 4–8 weeks (up to 12 times). The kidney is the dose-limiting organ and most patients experience a transient decline in blood cell counts. A concomitant infusion of an amino acid mixture can reduce kidney toxicity and increase the effective tumor dose. Other peptides currently under investigation, some of which have shown promising results, include Rhenium-188 (188Re)-P2045 and 90Y-αvβ3 antagonist.


Positron Emission Tomography Single Photon Emission Compute Tomography Octreotide Positron Emission Tomography Imaging Neuroendocrine Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank Dr Dik Kwekkeboom, at the Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, Netherlands, for generously providing images of a patient undergoing therapy with 177Lu-[DOTA0-Phe1-Tyr 3] Octreotide. We would also like to thank Drs Abraham, Schleif, and Lister-James of Berlex Inc., for providing the structure of the lung cancer treatment peptide, P2045. Dr R.Weiner is a consultant to Biogen Idec, Inc. The typing assistance of James Clarkin-Breslin and Kate Musselman is gratefully acknowledged.

No sources of funding were used to assist in the preparation of this review.


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Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Department of Diagnostic Imaging and TherapeuticsUniversity of Connecticut Health CenterFarmingtonUSA
  2. 2.Department of RadiologyThomas Jefferson University HospitalPhiladelphiaUSA
  3. 3.Division of Nuclear Medicine MC-2804University of Connecticut Health CenterFarmingtonUSA

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