Influence of rhTSH on [(18)F]fluorodeoxyglucose uptake by differentiated thyroid carcinoma.

The influence of serum TSH levels on fluorine-18 fluorodeoxyglucose (FDG) uptake by recurrences or metastases of differentiated thyroid carcinomas has not yet been clarified. The aim of this study was to ascertain whether the administration of recombinant human thyrotropin (rhTSH) stimulates FDG uptake by such lesions. In this prospective study, 30 patients with positive or equivocal thyroglobulin (Tg) levels and negative or equivocal iodine-131 and/or morphological imaging results (ultrasound, MRI, CT) underwent FDG positron emission tomography (PET) under exogenous TSH suppression and under exogenous TSH stimulation of serum levels by injection of rhTSH. The mean interval between the FDG-PET studies under these two conditions was 9.3+/-8.8 weeks. Serum TSH levels and free thyroid hormones were determined on each occasion. FDG uptake was quantitated using tumour to background ratios (TBRs) and standardised uptake values (SUVs). Under TSH suppression there was focal FDG accumulation in nine subjects (22 tumour-like lesions). The total number of foci was 45. After exogenous TSH stimulation, the number of patients in whom FDG foci were detected was 19, and the number of foci identified was 82 (78 tumour-like lesions). TBR of regions showing positive FDG contrast with either of the modalities averaged 2.54+/-1.89, and under stimulated TSH levels, 5.51+/-2.99 ( P<0.0001). Corresponding SUVs were 2.05+/-1.45 versus 2.77+/-1.58 ( P<0.001). In a small number ( n=4) of foci related to inflammatory lymph nodes, TBR and SUV were only marginally increased under TSH stimulation (2.01+/-0.38 and 1.07+/-0.38, respectively), and the values did not differ significantly from those obtained under suppression. These results provide the first direct evidence that TSH stimulates FDG uptake by differentiated thyroid carcinoma and that, therefore, FDG-PET is more accurate under rhTSH than under suppression.

[The value of positron emission tomography (PET) in the treatment of patients with cancer of unknown primary (CUP)]. / Bedeutung der Positronenemissionstomographie (PET) für die Behandlung von Patienten mit unbekanntem Primärtumor (CUP).

BACKGROUND: In patients with cancer of unknown primary median survival for localized disease is 20, for disseminated disease 7 months. After diagnostic procedures including MRI or endoscopy, the primary tumor is detected in less than 25%. In the study presented here the value of PET for detection of the primary tumor and a possible dissemination has been investigated and related to therapeutic regimens. PATIENTS AND METHODS: Between May 1998 and February 2001 a total of 52 patients with CUP syndrome, 18 females and 34 males, have been included. At first diagnosis, stage of disease was localized in 43 patients (35 lymphonodal, eight visceral), and disseminated in nine patients (Table 1). After a median of seven (range three to eleven) diagnostic procedures without detection of the primary tumor (Table 2) PET with fluorine-18-fluorodeoxyglucose was performed. RESULTS: Due to the PET result a primary tumor was suggested in 31/52 patients (60%), and confirmed in 21/52 patients (40%). In 16/43 patients (37%) with initially (before PET) localized disease dissemination was detected by PET only, despite various preceding diagnostic procedures (Figure 1). Overall, in 33/52 patients (63%) the PET result had major impact on selection of an individual treatment (Table 3), in case of initially localized disease in 30/43 patients (70%). CONCLUSION: In patients with CUP the PET result is not only of great value for detection of the primary tumor, but in case of initially localized disease also for diagnosis of a possible dissemination. The PET result often has relevant influence on therapeutic management.

[1-(11)C]Acetate as a quantitative perfusion tracer in myocardial PET.

UNLABELLED: Our objective was to investigate the properties of [1-(11)C]acetate as a quantitative perfusion tracer for myocardial PET studies. METHODS: We determined the flow dependence of the effective acetate extraction by a comparison with [(13)N]ammonia in 24 patients at rest (n = 8) and under pharmacologic vasodilation (n = 16). Furthermore, we compared the statistical quality of the perfusion values derived with both tracers. Quantification was based on an irreversible 2-compartment model for [(13)N]ammonia and a reversible 1-compartment model for [1-(11)C]acetate. Area-conserving polar maps were used to determine the correlation between the unidirectional uptake parameters of both tracers on a pixel-by-pixel basis for the whole left ventricular myocardium. RESULTS: A fit of a generalized Renkin-Crone formula to the data yielded the unidirectional acetate extraction fraction E(f) = 1 - 0.64e(-1.20/f). An extraction correction based on this formula led to good quantitative agreement of perfusion values derived with [(13)N]ammonia and [1-(11)C]acetate over the whole observed flow range (average difference of flow values, 3%; correlation coefficient, 0.96). This agreement proved the applicability of acetate as a quantitative perfusion tracer even under stress conditions. An analysis of the statistical properties of the parameter estimates showed, moreover, that statistical errors were reduced by a factor of nearly 2 in comparison with ammonia. CONCLUSION: [1-(11)C]acetate allows accurate quantification of myocardial perfusion with PET at rest as well as under stress conditions. The use of acetate leads to distinctly improved statistical accuracy for the perfusion estimates in comparison with ammonia. This accuracy facilitates the generation of reliable parametric polar maps, which are especially useful for clinical application of myocardial perfusion quantification.

Uptake of cis-4-[18F]fluoro-L-proline in urologic tumors.

UNLABELLED: Tumor uptake of the amino acid cis-4-[18F]fluoro-L-proline (cis-FPro) was studied with PET in eight patients with urologic tumors. METHODS: Three patients had primary renal cell carcinomas (RCCs), one had a local recurrence of RCC, one had squamous RCC, one had an adrenal hemangioma, one had inguinal metastases of penile squamous carcinoma, and one had suspected metastatic disease from prostate cancer. PET scans of the trunk were acquired at 1 and 3-5 h after intravenous injection of 400 MBq cis-FPro and compared with 18F-FDG PET scans and CT. RESULTS: None of the tumors or metastases showed significant uptake of cis-FPro. FDG uptake was seen in one of the three primary RCCs, in the local recurrence of RCC, in the squamous RCC, and in the metastases of penile cancer. CONCLUSION: Cis-FPro appears not to be a promising PET tracer in oncology.

[Follow-up of differentiated thyroid cancer patients using rhTSH--preliminary results]. / Nachsorge des differenzierten Schilddrüsenkarzinoms unter Verwendung von rhTSH--vorläufige Ergebnisse.

AIM: In the follow-up of patients with advanced stage thyroid cancer radioiodine scintigraphy, F-18-FDG PET and tumormarker hTg using stimulation with recombinant human TSH (rhTSH) were compared to the results of same diagnostic procedures during TSH-suppression or endogenous TSH-stimulation. METHODS: 30 patients were investigated in hypothyroidism and after application of rhTSH regarding the serum hormone concentrations, hTg, radioiodine scans and FGD-PET scans. RESULTS: Radioiodine avidity and FDG uptake were significantly higher in 7/30 and 3/5 patients, respectively, compared to endogenous stimulation or TSH-suppression. In about one third of patients hTg increased more than 30%. CONCLUSION: Our preliminary results indicate a sufficient feasibility and sensitivity of rhTSH not only in the follow-up by hTg and radioiodine scan but also in FDG-PET.

Whole-body kinetics and dosimetry of cis-4-[(18)F]fluoro-L-proline.

The whole-body distribution of 4-cis[(18)F]fluoro-L-proline (cis-FPro) was studied in six patients with urological tumors by PET. Based on the IMEDOSE and MIRDOSE procedures radiation absorbed doses were estimated from whole-body PET scans acquired at 1 and 3-5 h after i.v. injection of 400 MBq cis-FPro. Cis-FPro showed high retention in the renal cortex and a slight uptake in liver and pancreas. Urinary excretion ranged from 12 to 19% at 5 h p.i. Highest absorbed doses were found for the urinary bladder wall and the kidneys (44.1/44.0 microGy/mbq). The effective dose according to ICRP 60 was 15.1 microSv/mbq for adults. This leads to an effective dose of 6.0 mSv in a PET study using 400 MBq cis-FPro.

Localised disease in cancer of unknown primary (CUP): the value of positron emission tomography (PET) for individual therapeutic management.

BACKGROUND: Two to four percent of cancer patients present with CUP syndrome. Median survival for localised disease is 20 and for disseminated disease, seven months. For localised disease, curative treatment is more likely and individual therapeutic strategies become more important. After conservative diagnostic procedures including MRI, the primary is detected in less than 25%. The diagnostic value of PET and its influence on therapeutic strategies was evaluated. PATIENTS AND METHODS: Forty-two patients with localised CUP were investigated from 5 of 98 to 10 of 2000. The presenting site was lymph node metastasis in 34 and visceral metastasis in 8 patients. After a median of 7 (3-11) diagnostic procedures without detection of the primary, but evidence of localised disease, PET was performed with fluorine-18-fluorodeoxyglucose. RESULTS: In 26 of 42 patients (62%), a primary was suggested by PET and confirmed in 18 (43%). In 5 of 18 patients beyond localised disease, additional dissemination, not detected by previous diagnostic measures, was diagnosed by PET. Overall, dissemination was only detected only by PET in 16 of 42 patients (38%). In29 of 42 patients (69%), the PET result influenced selection of the definitive treatment. CONCLUSION: In CUP patients, PET has a certain impact on detection of the primary as well as of the disseminated disease. and may also have a certain impact on therapeutic management.

[F-18-FDG PET in autonomous goiter]. / F-18-FDG-PET bei Schilddrüsen-Autonomien.

AIM: Gain-of-function mutations of the thyrotropin receptor (TSHR) gene have been invoked as one of the major causes of toxic thyroid adenomas. This study evaluates F-18-FDG-PET in these patients. METHODS: Twenty patients with focal autonomous nodules and ten with disseminated autonomy were investigated the day before radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. RESULTS: F-18-FDG-Uptake was higher in patients than in controls. Focal autonomous nodules were associated with focally enhanced glucose metabolism. Disseminated autonomous goiters showed various patterns of focal or global hypermetabolism. CONCLUSION: Autonomous thyroid tissue caused by constitutive mutations of the TSH receptor is characterised by simultaneous increases in glucose and iodine metabolism which are correlated.

[F-qi-FDG PET of the thyroid gland in Graves' disease]. / F-18-FDG-PET der Schilddrüse bei Morbus Basedow.

AIM: This study evaluates F-18-FDG PET of the thyroid in Graves' disease. METHODS: Thirty patients were investigated the day before radioiodine therapy, 15 patients 3-10 days after radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. RESULTS: F-18-FDG uptake was higher in Graves' disease patients than in controls. Negative correlations of F-18-FDG uptake with half-life of radioiodine and absorbed radiation dose due to radioiodine therapy were found along with a positive correlation to autoantibody levels. CONCLUSION: Thus F-18-FDG PET is likely to give information on the biological activity of Graves' disease as well as on early radiation effects.

[Radioiodine therapy and radioiodine after-care in differentiated thyroid gland carcinomas]. / Radiojodtherapie und Radiojodnachsorge bei differenzierten Schilddrüsenkarzinomen.

Differentiated thyroid carcinoma (DTC) is a rare tumor with a generally good prognosis. Still some of these cancers cause the patient's death after many years of illness. Thus, treatment and aftercare have to be risk-adapted according to tumor type and staging. Surgery is the primary treatment for this tumor and its metastases, followed by therapy with radioiodine. According to the guidelines edited by the German Association for Nuclear Medicine (DGN)--work group for therapy--radioiodine therapy is an effective regimen with minimal side-effects. Radioiodine scintigraphy is the most important part of the aftercare program, together with the monitoring of the highly specific tumormarker thyreoglobulin. Other diagnostic modalities may be added when considering therapeutic options or confirming clinical suspicions. This paper aims at giving an update and overview on the applications of radioiodine, other radioisotopes and additional diagnostic and therapeutic options in differentiated thyroid cancer and related aspects of radiation exposure and radiation protection. As new therapeutic procedures and optimised diagnostic modalities become available, there is new hope for patients with locally advanced or metastatic DTC.