Three-dimensional radiobiological dosimetry (3D-RD) with 124I PET for 131I therapy of thyroid cancer

Radioiodine therapy of thyroid cancer was the first and remains among the most successful radiopharmaceutical (RPT) treatments of cancer although its clinical use is based on imprecise dosimetry. The positron emitting radioiodine, (124)I, in combination with positron emission tomography (PET)/CT has made it possible to measure the spatial distribution of radioiodine in tumors and normal organs at high resolution and sensitivity. The CT component of PET/CT has made it simpler to match the activity distribution to the corresponding anatomy. These developments have facilitated patient-specific dosimetry (PSD), utilizing software packages such as three-dimensional radiobiological dosimetry (3D-RD), which can account for individual patient differences in pharmacokinetics and anatomy. We highlight specific examples of such calculations and discuss the potential impact of (124)I PET/CT on thyroid cancer therapy.     

Pre-therapeutic 124I PET(/CT) dosimetry confirms low average absorbed doses per administered 131I activity to the salivary glands in radioiodine therapy of differentiated thyroid cancer

Purpose  

Salivary gland impairment following high activity radioiodine therapy of differentiated thyroid cancer (DTC) is a severe side effect. Dosimetric calculations using planar gamma camera scintigraphy (GCS) with ¹³¹I and ultrasonography (US) provided evidence that the average organ dose per administered ¹³¹I activity (ODpA) is too low to account for observed radiation damages to the salivary glands. The objective of this work was to re-estimate the ODpA using ¹²⁴I PET(/CT) as a more reliable approach than ¹³¹I GCS/US.     

Guidelines for radio-iodine (131I) therapy in Graves' disease and thyroid cancer

Radio-iodine (131I) therapy has been using in Graves' disease and well differentiated thyroid cancer. The rules of control in the discharge from radio-isotope hospital were notified in 1999 in Japan. Guideline of the 131I therapy in Graves' disease and thyroid cancer were prepared by sub-group of Japanese Society of Nuclear Medicine.     

Is empiric 131I therapy justified for patients with positive thyroglobulin and negative 131I whole-body scanning results?

The long-term monitoring of patients with differentiated thyroid carcinoma (DTC) is essential throughout the patient's life after total or nearly total thyroidectomy followed by 131I remnant ablation and thyroid hormone suppression of thyroid-stimulating hormone (TSH). Sensitive surveillance for DTC recurrences and metastases includes radioiodine diagnostic whole-body scanning (DWBS) and measurement of serum thyroglobulin (Tg) levels after endogenous or exogenous TSH stimulation. Serum Tg levels during thyroid hormone withdrawal usually are correlated well with the results of DWBS. In general, Tg levels undetectable by DWBS suggest complete remission, whereas detectable or elevated Tg concentrations are suggestive of the presence of 131I uptake in local or distant metastases. However, DTC patients with a positive Tg test and negative 131I DWBS results (Tg+ DWBS-) have been observed in follow-up studies. The management of these cases begets controversy. METHODS: We electronically searched Medline (1966-2004.3), Embase (1984-2003), the Cochrane Library (2004, 2nd edition), CNKI (1994-2004), and CBM-DISC (1978-2004). We also manually searched the Chinese Journal of Isotopes, Radiologia pratica, and the Chinese Journal of Endocrinology and Metabolism. RESULTS: Ten serial observations and 3 nonrandomized controlled trials were found. The available data showed that of 314 patients who were treated empirically with 131I, 194 (62%) of 314 displayed pathologic uptake in the thyroid bed, lung, bone, mediastinum, and lymph nodes. In studies with Tg-on and Tg-off data, 171 (63%) of 271 patients achieved a decrease in Tg. CONCLUSION: On the basis of data from recent studies, 131I therapy should be individualized according to clinical characteristics. More significantly, a decrease in Tg levels was achieved in 63% of DTC patients with Tg+ DWBS-, suggesting that 131I therapy does have a therapeutic effect when the Tg level is considered an index of tumor burden. The 62% positive posttherapy whole-body scanning results also indicated that a therapeutic dose of 131I could reveal approximately one half of previously undiagnosed lesions in some patients. Therefore, 131I therapy may be justified in patients with Tg levels of > 10 microg/L and DWBS- and who are at high risk of any recurrence.     

Prediction of absorbed dose to normal organs in thyroid cancer patients treated with 131I by use of 124I PET and 3-dimensional internal dosimetry software.

The objective of this work was to determine normal organ (131)I dosimetry in patients undergoing radioiodide therapy for thyroid cancer by use of serial scanning with (124)I PET. METHODS: A total of 26 patients who had papillary and follicular metastatic thyroid cancer and who were already enrolled in a Memorial Sloan-Kettering Cancer Center (131)I thyroid cancer protocol were selected for this study. Imaging before (131)I therapy consisted of multiple, whole-body (124)I PET studies over a period of 2-8 d, an (18)F-FDG PET scan and, for some, a diagnostic CT scan. With a set of in-house-developed software tools (3-dimensional internal dosimetry [3D-ID] and Multiple Image Analysis Utility [MIAU]), the following procedures were performed: all PET emission and transmission and CT image sets were aligned; half-life-corrected tomographic images of (131)I activity were integrated voxel by voxel to produce cumulated (131)I activity images; and the latter images were, in turn, convolved with a (131)I electron-photon point kernel to produce images of (131)I dose distribution. Cumulated activity values and calculated residence times obtained from our patient-specific dosimetry software (3D-ID) were used as inputs to OLINDA, and volume difference-adjusted comparisons were made between the mean dose estimates. RESULTS: With 3D-ID, dose volume histograms and mean doses were calculated for 14 organs, and results were expressed in Gy/GBq. The highest mean dose, 0.26 Gy/GBq, was seen in the right submandibular gland, whereas the lowest mean dose, 0.029 Gy/GBq, was seen in the brain. CONCLUSION: This is the first comprehensive study of normal organ dosimetry in patients by use of a quantitative tomographic imaging modality.     

Two-step targeting and dosimetry for small cell lung cancer xenograft with anti-NCAM/antihistamine bispecific antibody and radioiodinated bivalent hapten.

The "affinity enhancement system," a two-step targeting technique using bispecific antibody and radiolabeled bivalent hapten, has been reported to be useful for carcinoembryonic antigen-expressing tumors. The purpose of this study was to evaluate the efficacy of this method for targeting human small cell lung cancer using an antineural cell adhesion molecule antibody. METHODS: Antineural cell adhesion molecule/antihistamine bispecific antibody NK1NBL1-679 was prepared by coupling an equimolecular quantity of a Fab' fragment of NK1NBL1 to a Fab fragment of antihistamine 679. Athymic mice inoculated with NCI-H69 small cell lung cancer cells expressing neural cell adhesion molecule were administered bispecific antibody and then 48 h later 125I-labeled bivalent histamine hapten. 125I-labeled intact NK1NBL1 was injected into other groups of mice. Biodistributions were examined as a function of time. RESULTS: In mice of the two-step targeting, tumor uptake was 2.5 +/- 0.2, 3.2 +/- 0.4, 6.4 +/- 2.0, 7.2 +/- 2.7, 6.1 +/- 2.1 and 2.2 +/- 0.4 %ID/g at 5, 30 min, 5, 24, 48 and 96 h, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 1.4 +/- 1.1, 10.8 +/- 13.2 and 4.6 +/- 4.7, respectively, at 5 h, whereas 125I-labeled NK1NBL1 showed a tumor uptake of 5.7 +/- 0.4 %ID/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 0.3 +/- 0.1, 1.1 +/- 0.2 and 0.9 +/- 0.1, respectively, at 5 h. These results were confirmed by autoradiographic studies, which demonstrated clear tumor-to-normal tissue contrast. Dosimetry showed that the affinity enhancement system could enhance the therapeutic potential of the antineural cell adhesion molecule antibody NK1NBL1. CONCLUSION: This two-step targeting method seems promising for the diagnosis and therapy of small cell lung cancer.     

Radiation protection and dosimetry issues for patients with prostate cancer after I-125 low-dose-rate brachytherapy permanent implant

PurposeThe aim of this work was to analyze the exposure rates measured in the proximity of patients who underwent prostate low-dose-rate brachytherapy with I-125 implant. Effective doses to relatives and to population were computed to estimate the time to reach radioprotection dose constraints.Methods and MaterialsMeasurements were obtained from 180 patients, whereas the body mass index was calculated and reported for 77 patients. The day after the implant, $\dot{K}$ measurements were conducted at various skin distances and positions and converted to effective doses. A theoretical model was developed to estimate effective doses from total implanted activity. The latter was approximated with a 10-mL vial inside the patient.ResultsThe $\dot{K}$ measurements showed a low correlation with the total implanted activity, albeit an increasing trend of $\dot{K}$ was observed on increasing the activity. A stronger correlation was found between body mass index and $\dot{K}$ measurements.The effective dose to population is in general lower than dose constraints as well as the effective doses to relatives, with the exception of children and pregnant women, who command special precautions. We report differences between the experimental model– and theoretical model–based dose evaluation together with their comparison with previous studies found in literature.ConclusionsBased on the $\dot{K}$ measurements and the results of the present analysis, it is possible to provide the patient with radiation safety instructions specifically tailored to his relatives’ habits and working environment.     

Comparison of (123)I and (131)I for whole-body imaging in thyroid cancer.

We compared the diagnostic sensitivities of (123)I and (131)I whole-body imaging in differentiated thyroid cancer. METHODS: Twelve thyroidectomized patients (3 previously treated with (131)I) were studied. After a period of thyroid hormone withdrawal, whole-body imaging was performed approximately 24 and 72-96 h after administration of 74-185 MBq (2-5 mCi) (123)I and 111-185 MBq (3-5 mCi) (131)I, respectively. RESULTS: Both (123)I and (131)I revealed residual thyroid tissue, present in 9 patients. (131)I detected metastases in 5 studies of 4 patients. In 4 of 5 studies, (123)I missed metastases shown by (131)I in 8 body regions including the neck, mediastinum, lungs, and bone and detected 3 other sites of metastasis only in retrospect. No lesion was better seen with (123)I than with (131)I. CONCLUSION: Although (123)I is adequate for imaging residual thyroid tissue, it appears to be less sensitive than (131)I for imaging thyroid cancer metastases.     

Relative therapeutic efficacy of (125)I- and (131)I-labeled monoclonal antibody A33 in a human colon cancer xenograft.

A33, a monoclonal antibody that targets colon carcinomas, was labeled with (125)I or (131)I and the relative therapeutic efficacy of the 2 radiolabeled species was compared in a human colon cancer xenograft system. METHODS: Nude mice bearing human SW1222 colon carcinoma xenografts were administered escalating activities of (125)I-A33 (9.25-148 MBq) or (131)I-A33 (0.925-18.5 MBq), (125)I- and (131)I-labeled control antibodies, unlabeled antibody, or no antibody. The effects of treatment were assessed using the endpoints of tumor growth delay and cure. RESULTS: Tumor growth delay increased with administered activity for all radiolabeled antibodies. Approximately 4.5 times more activity was required for (125)I-A33 to produce therapeutic effects that were equivalent to those of (131)I-A33. This ratio was approximately 7 for a nonspecific, noninternalizing isotype-matched, radiolabeled control antibody. Unlabeled A33 antibody had no effect on tumor growth. Approximately 10 times more activity of (125)I-A33 produced toxicity similar to that of (131)I-A33, and this ratio fell to approximately 6 for radiolabeled control antibody. CONCLUSION: Treatment with (125)I-A33 resulted in a relative therapeutic gain of approximately 2 compared with (131)I-A33 in this experimental system.     

Radiation dose to the testes after 131I therapy for ablation of postsurgical thyroid remnants in patients with differentiated thyroid cancer.

Radioiodine-131 is used in differentiated thyroid cancer (DTC) for ablation of postsurgical thyroid remnants and destruction of metastases. The question may be raised of whether 131I treatment of DTC in male patients may give an irradiation dose to the testes that could impair fertility. Few data in the literature concern the dose absorbed by the testes after 1311 therapy for DTC. Because 131I kinetics may be altered by the hypothyroid condition commonly present at the time of treatment and by the radioiodinated iodoproteins released by the damaged thyroid tissue, the dose values reported in the International Commission on Radiological Protection (ICRP) tables for euthyroid men may not be appropriate. To clarify this problem, three male subjects undergoing 131I therapy for ablation of thyroid remnants shortly after thyroidectomy for DTC were studied. METHODS: The mean administered activity was 1256 MBq, and the duration of the study was 2 wk. The gamma dose was measured by thermoluminescent dosimeters (TLDs) applied to the lower poles of the testes. Correction factors were calculated for the distance of the TLD from the center of the testes and for attenuation by the testes of the gamma rays reaching the TLD. After correction, the gamma dose to the testes ranged from 21 to 29 mGy. The gamma dose calculated by the Medical Internal Radiation Dose (MIRD) method from blood and urine samples was similar (18-20 mGy) to that measured by TLDs. The beta dose was estimated by the MIRD method from blood activity and testicular volume and ranged between 14 and 31 mGy. Results: The total (beta and gamma) doses to testes were 30, 33 and 43 microGy/MBq in the three subjects. CONCLUSION: These values are close to those derived from the ICRP tables (26-37 microGy/MBq 131I) for euthyroid subjects. The present data indicate that significant irradiation is delivered to the testes after the administration of the 131I ablative dose to thyroidectomized patients. The relevance of the radiation absorbed by testes on fertility remains to be established.     

甲状腺乳头状癌患者术后首次131I治疗后辐射剂量率的影响因素及出院时间的探讨

目的 探讨甲状腺乳头状癌(PTC)患者术后首次131I治疗后影响辐射剂量率降低的相关因素,并预估其住院隔离时间。方法 选取2015年5月至2018年11月于南方医科大学珠江医院住院并首次行131I治疗的PTC患者167例,其中男性43例、女性124例,年龄(37.14± 12.00)岁。将所有患者按治疗剂量分为高剂量组(63例)和低剂量组(104例),于治疗后24、48、72、96 h时测量距离患者1 m处的辐射剂量率,将治疗后患者体内滞留131I活度为400 MBq时的时间点定为出院时间。采用多重线性回归方法分析影响辐射剂量率降低的相关因素。组间比较采用两独立样本非参数检验或两独立样本t检验。结果 PTC患者首次行131I治疗后的辐射剂量率随时间推移迅速下降,高剂量组治疗后的24、48 h辐射剂量率[(70.62±34.45)、15.64 μSv/h]明显高于低剂量组[(11.27±5.13)、2.03 μSv/h],且差异均有统计学意义(t=-13.581、-7.952,均P <0.01)。81.0%(51/63)和90.5%(57/63)的高剂量组患者分别可在治疗48 h和72 h后出院,99%(103/104)的低剂量组患者可在治疗24 h后出院。多重线性回归分析显示,131I剂量和2 h摄碘率对高剂量组24 h辐射剂量率的影响有统计学意义(F=9.23,复相关系数R2=0.212,P<0.01),高剂量组24 h辐射剂量率与2 h摄碘率和131I剂量呈正相关;性别、24 h摄碘率和残甲法3对高剂量组48 h辐射剂量率的影响有统计学意义(F=34.45,复相关系数R2=0.622,P<0.01),48 h辐射剂量率与24 h摄碘率和残留甲状腺体积呈正相关,与性别呈负相关;131I剂量和24 h饮水量对低剂量组24 h辐射剂量率的影响有统计学意义(F=12.76,复相关系数R2=0.186 ,P<0.01),低剂量组24 h辐射剂量率与131I剂量呈正相关,与24 h饮水量呈负相关。结论 PTC术后患者首次131I治疗24 h后,影响其辐射剂量率降低的主要因素是服用131I的剂量,而48 h后的主要影响因素是24 h甲状腺摄碘率、残留甲状腺体积和性别。低剂量组和高剂量组平均住院时间分别为1 d和2 d左右。     

Synthesis and biological evaluation of copper-64 radiolabeled [DUPA-6-Ahx-(NODAGA)-5-Ava-BBN(7-14)NH2], a novel bivalent targeting vector having affinity for two distinct biomarkers (GRPr/PSMA) of prostate cancer

Gastrin-releasing peptide receptors (GRPr) and prostate-specific membrane antigen (PSMA) are two identifying biomarkers expressed in very high numbers on prostate cancer cells and could serve as a useful tool for molecular targeting and diagnosis of disease via positron-emission tomography (PET). The aim of this study was to produce the multipurpose, bivalent [DUPA-6-Ahx-(⁶⁴Cu-NODAGA)-5-Ava-BBN(7-14)NH₂] radioligand for prostate cancer imaging, where DUPA = (2-[3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid), a small-molecule, PSMA-targeting probe, 6Ahx = 6-aminohexanoic acid, 5-Ava = 5-aminovaleric acid, NODAGA = [2-(4,7-biscarboxymethyl)-1,4,7-(triazonan-1-yl)pentanedioic acid] (a derivative of NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid)), and BBN(7-14)NH₂ = bombesin, a GRPr-specific peptide targeting probe.MethodsThe PSMA/GRPr dual targeting ligand precursor [DUPA-6-Ahx-K-5-Ava-BBN(7-14)NH₂], was synthesized by solid-phase and manual peptide synthesis, after which NODAGA was added via manual conjugation to the ε-amine of lysine (K). The new bivalent GRPr/PSMA targeting vector was purified by reversed-phase high performance liquid chromatography (RP-HPLC), characterized by electrospray-ionization mass spectrometry (ESI-MS), and metallated with ⁶⁴CuCl₂ and ^natCuCl₂. The receptor binding affinity was evaluated in human, prostate, PC-3 (GRPr-positive) and LNCaP (PSMA-positive) cells and the tumor-targeting efficacy determined in severe combined immunodeficient (SCID) and athymic nude mice bearing PC-3 and LNCaP tumors. Whole-body maximum intensity microPET/CT images of PC-3/LNCaP tumor-bearing mice were obtained 18 h post-injection (p.i.).ResultsCompetitive binding assays in PC-3 and LNCaP cells indicated high receptor binding affinity for the [DUPA-6-Ahx-(^natCu-NODAGA)-5-Ava-BBN(7-14)NH₂] conjugate. MicroPET scintigraphy in PC-3/LNCaP tumor-bearing mice indicated that xenografted tumors were visible at 18 h p.i. with collateral, background radiation also being observed in non-target tissue.ConclusionsDUPA-6-Ahx-(⁶⁴Cu-NODAGA)-5-Ava-BBN(7-14)NH₂] targeting vector, as described herein, is the first example of a dual GRPr-/PSMA-targeting radioligand for molecular of imaging prostate tumors. Detailed in vitro studies and microPET molecular imaging investigations of [DUPA-6-Ahx-(⁶⁴Cu-NODAGA)-5-Ava-BBN(7-14)NH₂ in tumor-bearing mice indicate that further studies are necessary to optimize uptake and retention of tracer in GRPr- and PSMA-positive tissues.     

Clinical impact of (18)F-FDG PET in thyroid carcinoma patients with elevated thyroglobulin levels and negative (131)I scanning results after therapy.

18F-FDG PET has been shown to effectively detect differentiated thyroid carcinoma (DTC) metastases with impaired iodine-trapping ability. This article evaluates the potential contribution of FDG PET in the follow-up of patients with differentiated thyroid carcinoma, elevated thyroglobulin (Tg) levels, and negative whole-body scan results obtained after high doses of (131)I. METHODS: We prospectively assessed the ability of FDG to detect metastases in 37 DTC patients who had undergone total thyroidectomy and radioactive ablation and presented with persistent disease, as assessed from elevated Tg levels and negative results of whole-body scans performed after therapeutic doses of (131)I. Additional conventional imaging procedures were performed to detect residual disease, and the patients were divided into 2 groups: group 1, with positive conventional imaging findings (n = 10), and group 2, with negative conventional imaging findings (n = 27). RESULTS: FDG PET showed positive findings in 28 patients and accurately localized tumor sites in 89% of them. In group 1, FDG PET confirmed 17 of 18 previously known tumor sites and detected 11 additional sites. In group 2, FDG PET findings were positive in 19 of 27 patients with no previously detected metastases. PET was effective for both low- and high-stage tumors. The FDG data led to a change in the clinical management of 29 of 37 patients with further surgical resection in 23 patients, 14 of whom achieved disease-free status, and external radiation therapy in 4 patients. CONCLUSION: FDG PET is able to detect metastases undetected by (131)I posttherapy whole-body scanning in patients with elevated Tg levels. It should be proposed as a first-line investigation in patients with persistent disease but negative findings on (131)I whole-body scans after treatment.     

Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer

Purpose

Positron emission tomography (PET) with choline tracers has found widespread use for the diagnosis of prostate cancer (PC). However, choline metabolism is not increased in a considerable number of cases, whereas prostate-specific membrane antigen (PSMA) is overexpressed in most PCs. Therefore, a ⁶⁸Ga-labelled PSMA ligand could be superior to choline tracers by obtaining a high contrast. The aim of this study was to compare such a novel tracer with standard choline-based PET/CT.

Methods

Thirty-seven patients with biochemical relapse of PC [mean prostate-specific antigen (PSA) 11.1?±?24.1 ng/ml, range 0.01–116] were retrospectively analysed after ¹⁸F-fluoromethylcholine and ⁶⁸Ga-PSMA PET/CT within a time window of 30 days. Radiotracer uptake that was visually considered as PC was semi-quantitatively analysed by measuring the maximum standardized uptake values (SUV_max) of the scans acquired 1 h after injection of ⁶⁸Ga-PSMA complex solution (median 132 MBq, range 59–263 MBq) and ¹⁸F-fluoromethylcholine (median 237 MBq, range 114–374 MBq), respectively. In addition, tumour to background ratios were calculated.

Results

A total of 78 lesions characteristic for PC were detected in 32 patients using ⁶⁸Ga-PSMA PET/CT and 56 lesions were detected in 26 patients using choline PET/CT. The higher detection rate in ⁶⁸Ga-PSMA PET/CT was statistically significant (p?=?0.04). In five patients no lesion was found with both methods. All lesions detected by ¹⁸F-fluoromethylcholine PET/CT were also seen by ⁶⁸Ga-PSMA PET/CT. In ⁶⁸Ga-PSMA PET/CT SUV_max was clearly (>10 %) higher in 62 of 78 lesions (79.1 %) and the tumour to background ratio was clearly (>10 %) higher in 74 of 78 lesions (94.9 %) when compared to ¹⁸F-fluoromethylcholine PET/CT.

Conclusion

⁶⁸Ga-PSMA PET/CT can detect lesions characteristic for PC with improved contrast when compared to standard ¹⁸F-fluoromethylcholine PET/CT, especially at low PSA levels.     

PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions

Purpose

Prostate-specific membrane antigen (PSMA) is a cell surface protein with high expression in prostate carcinoma (PC) cells. Recently, procedures have been developed to label PSMA ligands with ⁶⁸Ga, ^99mTc and ^123/124/131I. Our initial experience with Glu-NH-CO-NH-Lys-(Ahx)-[⁶⁸Ga(HBED-CC)](⁶⁸Ga-PSMA) suggests that this novel tracer can detect PC relapses and metastases with high contrast. The aim of this study was to investigate its biodistribution in normal tissues and tumour lesions.

Methods

A total of 37 patients with PC and rising prostate-specific antigen (PSA) levels were subjected to ⁶⁸Ga-PSMA positron emission tomography (PET)/CT. Quantitative assessment of tracer uptake was performed 1 and 3 h post-injection (p.i.) by analysis of mean and maximum standardized uptake values (SUV_mean/max) of several organs and 65 tumour lesions. Subsequently, tumour to background ratios were calculated.

Results

The PET/CT images showed intense tracer uptake in both kidneys and salivary glands. Moderate uptake was seen in lacrimal glands, liver, spleen and in small and large bowel. Quantitative assessment revealed excellent contrast between tumour lesions and most normal tissues. Of 37 patients, 31 (83.8 %) showed at least one lesion suspicious for cancer at a detection rate of 60 % at PSA <2.2 ng/ml and 100 % at PSA >2.2 ng/ml. Median tumour to background ratios were 18.8 (2.4–158.3) in early images and 28.3 (2.9–224.0) in late images.

Conclusion

The biodistribution of the novel ⁶⁸Ga-PSMA tracer and its ability to detect PC lesions was analysed in 37 patients. Within healthy organs, kidneys and salivary glands demonstrated the highest radiotracer uptake. Lesions suspicious for PC presented with excellent contrast as early as 1 h p.i. with high detection rates even at low PSA levels.     

High-dose-rate brachytherapy combined with long-term hormonal therapy for high-risk prostate cancer: results of a retrospective analysis

Purpose High-dose-rate (HDR) brachytherapy combined with hormonal therapy (HTx), without the addition of external beam radiation therapy (EBRT) for high-risk prostate cancer was evaluated retrospectively. Materials and Methods Between May 1995 and April 2002, 35 patients with prostate cancer [Stage≥T2b (UICC 1997) or tumor grading=3 or prostate-specific antigen (PSA) level≥20 ng/mL] were treated with HDR brachytherapy combined with HTx. Most patients (74%) had two or more of these factors. All patients received Iridium-192 HDR brachytherapy with a total dose of 54 Gy/9 fractions/5 days (48 Gy/8 fractions/5 days for the first 6 cases) in one implant session. The median neoadjuvant HTx [luteinizing hormone-releasing hormone (LH-RH) agonist and antiandrogen] period was 7 months. The median adjuvant HTx (ATH) (LH-RH agonist) period was 40 months, and median follow-up was 57 months (range, 23–117 months). Results The 5-year actuarial biochemical control, local control, and disease-free rates were 62%, 96%, and 76% respectively. No patients experienced local and/or regional relapse without distant progression. The 5-year actuarial cause-specific survival and overall survival rates were 89% and 87%, respectively. The acute and late toxicity were moderate and well tolerated. Conclusion HDR brachytherapy plus long-term HTx is at least as effective as conventional EBRT plus long-term HTx.     

Loose seeds vs. stranded seeds: a comparison of critical organ dosimetry and acute toxicity in (125)I permanent implant for low-risk prostate cancer

PURPOSE: To compare the critical organ dosimetry and toxicity of loose seeds (LS) with stranded seeds (SS) in (125)I permanent implant for low-risk prostate cancer. METHODS AND MATERIALS: Two cohorts of 20 patients each were treated in Institutional Review Board-approved protocols designed to assess prostate edema and seed stability using MR-CT fusion on Days 0, 7, and 30 after permanent implant. (125)I LS were used for one cohort and (125)I SS for the other. Rectal wall dosimetry was compared for the two cohorts using RV100 and RD1cc and urethral dosimetry using UD5, UD30, and UV150. Statistical comparisons were performed using unpaired Student's t test. RESULTS: At each time point (Days 0, 7, and 30), both the mean RD1 cc (SS: 123.1, 139.7, and 156.1 Gy vs. LS: 90.2, 104, and 129.4 Gy, respectively) and the mean RV100 (SS: 0.63, 1.0, and 1.4 cc vs. LS: 0.2, 0.4, and 0.73 cc, respectively) were significantly higher for strands (all p-values<0.01). Only 1 patient developed radiotherapy oncology group (RTOG) Grade 1 acute rectal toxicity in the loose seed cohort, whereas 3 patients had Grade 1 and 1 patient had Grade 2 toxicity with strands. The mean percentage increase of UD5 (7.7% LS vs. 24.6% SS; p=0.004) and UD30 (5% LS vs. 15.9% SS; p=0.02) from preplan to Day 30 was higher for strands. The increase in UV150 from baseline to Day 30 was significantly higher for strands (0.2 vs. 0.06 cc; p=0.01). Urinary toxicity was similar in both cohorts. CONCLUSIONS: SS resulted in higher dose to urethra and rectal wall compared with LS on postimplant dosimetry. A trend toward higher acute rectal toxicity rate was observed for SS.