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11C-metomidate PET imaging of adrenocortical cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2003 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070 (Paper) 1619-7089 (Online), Vol. 30, no 3, 403-410 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 30, no 3, 403-410 p.
URN: urn:nbn:se:uu:diva-91693OAI: oai:DiVA.org:uu-91693DiVA: diva2:164511
Available from: 2004-05-03 Created: 2004-05-03 Last updated: 2011-03-23Bibliographically approved
In thesis
1. New Diagnostic and Therapeutic Approaches in Adrenocortical Cancer
Open this publication in new window or tab >>New Diagnostic and Therapeutic Approaches in Adrenocortical Cancer
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Ny Diagnostik och Behandling av Patienter med Binjurebarkscancer
Abstract [en]

Adrenocortical cancer (ACC) is a rare disease that is often difficult to diagnose, and therefore often presents at an advanced stage. Various cytotoxic treatments have been tried with little success. Evaluation of new diagnostic methods and improvement of medical therapies are therefore crucial.

The diagnostic potential of 11C-metomidate positron emission tomography (PET) was evaluated in eleven ACC patients. PET visualized all viable tumors with high tracer uptake, including two lesions that CT failed to detect. Necrotic or fibrotic tumors were PET negative. Medication with adrenal steroid inhibitors and chemotherapy may decrease the tracer uptake.

We performed a phase-II study with streptozocin and o,p’-DDD (SO) combination therapy in 40 ACC patients. The SO therapy was found to have impact on the disease-free interval (P = 0.02) as well as on survival (P = 0.01) in patients who received adjuvant therapy after curative resection. Complete or partial response was obtained in 36.4% of patients with measurable disease.

The efficacy and tolerability of combination therapy with vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) were evaluated in eleven patients with advanced ACC after failure of SO therapy. The median survival was 21 months from the start of treatment. A partial response was achieved in two patients. Adverse events were mainly restricted to grade 1-2 toxicities, and grade 3 toxicities were observed in only two cycles.

We tested 21 ACC tumors to analyze the expression of receptor tyrosine kinases and 15 ACC for mutation analysis of c-Kit exon 11, which can be targeted by antagonists such as imatinib. All ACCs expressed one or more kinases: c-Kit in 19 ACC and phospho-c-Kit in three while 14 ACCs expressed PDGFR-beta, suggesting the potential usefulness of tyrosine kinase inhibitors. No c-Kit mutations were detected in exon 11. Further evaluation of other mutations targeted by this drug may be needed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 74 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1346
Medicine, Adrenocortical cancer, Positron Emission Tomography, Metomidate, Combination chemotherapy, Streptozocin, op'-DDD, OPEC, Disease-free Interval, Survival, Responses, Side effects, Receptor protein-tyrosine kinases, c-Kit, Phospho-c-Kit, PDGFRβ, Mutation, Imatinib, Medicin
National Category
Dermatology and Venereal Diseases
urn:nbn:se:uu:diva-4243 (URN)91-554-5954-4 (ISBN)
Public defence
2004-05-26, Enghoffsalen, Entrance 50, ground floor, University Hospital, SE-751 85, Uppsala, 13:15
Available from: 2004-05-03 Created: 2004-05-03Bibliographically approved

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